Unit 3

Structure of Eukaryotes & Control of Microorganisms

*Characteristics, Morphology, Reproduction, Physiology and Pathogenicity

• Fungi
• Algae
• Protozoa
* Control of Microorganisms
• Physical control
• Chemical control
• Antibiotics
 Unit 3 - FUNGI
 Fungi - Importance of fungi in various field applications
 Morphology of fungi
 Structural characteristics and ecological association of fungi
 Classification of fungi
 Sexual and Asexual Reproduction of fungi
 Cultivation of fungi
 Preservation techniques of fungi
 Fungal toxins
FUNGI
 Microbiologists use the term fungus [pl., fungi; Latin fungus,
mushroom] to describe eucaryotic organisms that are spore-bearing,
have absorptive nutrition, lack chlorophyll, and reproduce sexually and
asexually.

 Scientists who study fungi are mycologists [Greek mykes,

mushroom, and logos, science], and the scientific discipline devoted to
fungi is called mycology.

 The study of fungal toxins and their effects is called

mycotoxicology, and the diseases caused by fungi in animals are known
as mycoses (s., mycosis).
 According to the universal phylogenetic tree, fungi are members
of the domain Eucarya.

 Morphological, biochemical and molecular phylogenetic

analyses demonstrate that the Fungi constitute a monophyletic
group.

 They are sometimes referred to as the true fungi or Eumycota

[Greek eu - true, and myke - fungus].
 DISTRIBUTION

 Fungi are primarily terrestrial organisms, although a

few are freshwater or marine.

 They have a global distribution from polar to tropical

regions.

 Many are pathogenic and infect plants and animals.

 Fungi also form beneficial relationships with other

organisms.
 For example, the vast majority of vascular plant roots form

associations (called mycorrhizae) with fungi.

 Fungi also are found in the upper portions of many plants.

 These endophytic fungi affect plant reproduction and

palatability to herbivores.

 Lichens are associations of fungi and photosynthetic protists or

cyanobacteria.
 IMPORTANCE
 Fungi are important to humans in both beneficial and harmful ways.

 Fungi act as decomposers, a role of enormous significance. They

degrade complex organic materials in the environment to simple organic
compounds and inorganic molecules.

 Fungi are a major cause of disease. Plants are particularly vulnerable

to fungal diseases because fungi can invade leaves through their
stomates.

 Fungi also cause many diseases of animals and humans.

 Fungi, especially the yeasts, are essential to many industrial
processes involving fermentation.

Eg: Making of bread, wine, and beer.

 Fungi also play a major role in the preparation of some

Cheeses, Soy sauce, and Sufu;

 In the commercial production of many organic acids (Citric,

gallic) and certain drugs (Ergometrine, Cortisone); and

 In the manufacture of many antibiotics (Penicillin,

Griseofulvin) and the immunosuppressive drug cyclosporin.
Some Mycotoxicoses Produced by Fungal Mycotoxins in Domestic
Animals
 STRUCTURE
 The body or vegetative structure of a fungus is
called a thallus.

 It varies in complexity and size, ranging from

the single-cell microscopic yeasts to multicellular
molds, macroscopic puffballs, and mushrooms.

 The fungal cell usually is encased in a cell wall

of chitin.

 Chitin is a strong but flexible nitrogen

containing polysaccharide consisting of N-
acetylglucosamine residues
 YEAST
 A yeast is a unicellular fungus that
has a single nucleus and reproduces
either asexually by budding and
transverse division or sexually through
spore formation.

 Each bud that separates can grow

into a new yeast, and some group
together to form colonies.

 Yeast cells are commonly spherical

to egg shaped.

 They lack flagella but possess most

of the other eucaryotic organelles.
 MOLDS
 The thallus of a mold consists of long,
branched, threadlike filaments of cells
called hyphae that form a mycelium, a
tangled mass or tissue like aggregation
of hyphae.
 In some fungi, protoplasm streams
through hyphae, uninterrupted by cross
walls. These hyphae are called
coenocytic or aseptate.
 The hyphae of other fungi have cross
walls called septa with either a single
pore or multiple pores that enable
cytoplasmic streaming. These hyphae are
termed septate. Mutiporate
hyphae diagram
 Hyphae are composed of an outer cell wall and an
inner lumen, which contains the cytosol and
organelles.

 A plasma membrane surrounds the cytoplasm and

lies next to the cell wall.

 The filamentous nature of hyphae results in a large

surface area relative to the volume of cytoplasm.

 This makes adequate nutrient absorption possible.

FUNGAL HYPHAL
MORPHOLOGY
DIMORPHIC FUNGI

 Many fungi, especially those that cause diseases in humans

and animals, are dimorphic - that is, they have two forms.

 Dimorphic fungi can change from the yeast (Y) form in the
animal to the mold or mycelial form (M) in the external
environment in response to changes in various environmental
factors (nutrients, CO2 tension, oxidation-reduction potentials,
temperature). This shift is called the YM shift.
Some Medically Important Dimorphic Fungi
 NUTRITION AND METABOLISM
 Fungi grow best in dark, moist habitats and are found wherever organic material is
available.

 Most fungi are saprophytes, securing their nutrients from dead organic material.

 They are chemoorganoheterotrophs and use organic compounds as a source of

carbon, electrons, and energy.

 Glycogen is the primary storage polysaccharide in fungi.

 Most fungi use carbohydrates (preferably glucose or maltose) and nitrogenous

compounds to synthesize their own amino acids and proteins.

 Fungi usually are aerobic. Some yeasts, however, are facultatively anaerobic and can
obtain energy by fermentation. Obligately anaerobic fungi are found in the rumen of
cattle.

 Many fungal fermentations are of industrial importance, such as the production of

ethyl alcohol in the manufacture of beer and wine.
 ECOLOGY OF FUNGI
 Fungi, together with bacteria are the
principal decomposers in the biosphere

 Fungi are virtually the only organisms

capable of breaking down cellulose and
lignin

 Fungi have entered into fascinating

symbioses with a variety of life forms

* Obligate symbiosis – Essential for

fungus survival

* Facultative symbiosis – Non essential

ECOLOGY OF FUNGI
Types of symbioses

-Pathogens and parasites benefit at the

expense of their host

-Commensals benefit one partner but do not

harm or benefit the other

-Mutualistic relationships benefit both partners

ECOLOGY OF FUNGI
Endophytic fungi live in the intercellular spaces inside plants
►Some fungi protect their hosts from herbivores by producing
toxins
► Rye grass is more resistant to aphid feeding in the presence of
endophytes
 LICHENS
 Lichens are the association between specific
ascomycetes (a fungus) and certain genera of either
green algae or cyanobacteria.

 In a lichen, the fungal partner is termed the

mycobiont and the algal or cyanobacterial partner, the
phycobiont.

 In the past the lichen symbiosis was considered to

be a mutualistic interaction.

 It recently has been found that a lichen forms only

when the two potential partners are nutritionally
deprived.
 In nutrient-limited environments, the relationship between the fungus and its
photosynthetic partner has coevolved to the point where lichen morphology and
metabolic relationships are extremely stable.

 The characteristic morphology of a given lichen is a property of the association

and is not exhibited by either symbiont individually.

 Because the phycobiont is a photoautotroph-dependent only on light, carbon

dioxide, and mineral nutrients—the fungus can get its organic carbon directly from
the alga or cyanobacterium.
 The fungus often obtains nutrients from its partner by projections of fungal
hyphae called haustoria, which penetrate the phycobiont cell wall.

 It also uses the O2 produced during phycobiont photophosphorylation in

carrying out respiration.

 In turn the fungus protects the phycobiont from high light intensities, provides
water and minerals to it, and creates a firm substratum within which the
phycobiont can grow protected from environmental stress.

 The invasive nature of the fungal partner is why lichens are considered parasitic
relationships.
 MYCORRHIZAE
 Mycorrhizae (derived from the Greek “fungus root”) are
mutualistic relationships that develop between most plants and a
limited number of fungal species.

 Both partners in mutualistic relationships are dependent on the

activities of the other and as such have coevolved.

 In this case, fungi colonize the roots of about 80% of all higher
plants as well as ferns and mosses and they use photosynthetically
derived carbohydrate provided by their host.

 In return, they provide a number of services for their plant hosts,

including enhanced nutrient uptake.
 Arbuscular (endo) mycorrhizae
-Hyphae penetrate the root cell wall
-By far the most common (70% of all species)
-Fungal partners are Glomeromycetes
 Ectomycorrhizae
-Hyphae surround but do not penetrate the root cells
-Most hosts are forest trees (pines,oaks)
-Fungal partners are mostly Basidiomycetes
Advantages Of Mycorrhizae
CLASSIFICATION OF FUNGI
ZYGOMYCETES

• Lower fungi

• Broad, septate hyphae

• Asexual spores -
Sporangiospores: present
within a swollen sac- like
structure called Sporangium
ZYGOMYCETES

• Sexual spores -
Zygospore:
• a resting, thick walled
cell in between hyphae

e.g. Rhizopus, Mucor

ASCOMYCETES

• Includes both yeasts & filamentous fungi

• Narrow, septate hyphae
• Asexual spores are called conidia borne on
conidiophore
 ASCOMYCETES

• Sexual spores called ascospores

are present within a sac like
structure called Ascus.

• Several asci may be seen within

a fruiting body as seen in
Penicillium, Aspergillus

Each ascus has 4 to 8 ascospores.

BASIDIOMYCETES

• Sexual fusion results in the formation of a club

shaped organ called base or basidium which bear
spores called basidiospores
DEUTEROMYCETES
OR
FUNGI IMPERFECTI

• Grow as molds as well as yeasts.

• Asexual stage – conidia
e.g. Candida, Cryptococcus
REPRODUCTION
 Reproduction in fungi can be either asexual or sexual.
 Asexual reproduction is accomplished in several ways:
1. A parent cell can undergo mitosis and divide into two daughter
cells by a central constriction and formation of a new cell wall.

Transverse fission forming new cell wall

2. Mitosis in vegetative cells may be concurrent with budding to

produce a daughter cell. This is very common in the yeasts.
3. The most common method of asexual reproduction is spore
production. Asexual spore formation occurs in an individual fungus through
mitosis and subsequent cell division.
 There are several types of asexual spores,
each with its own name:
a. A hypha can fragment (by the
separation of hyphae through
splitting of the cell wall or septum) to
Hyphal fragmentation
resulting in arthroconidia
form cells that behave as spores. (arthrospores)

These cells are called arthroconidia

or arthrospores. Terminal
chlamydospore

b. If the cells are surrounded by a thick

wall before separation, they are called Chlamydospore
within a hyphae

chlamydospores.
c. If the spores develop within a sac
(sporangium; pl., sporangia) at a hyphal tip,
they are called sporangiospores.

d. If the spores are not enclosed in a sac but

produced at the tips or sides of the hypha, they
are termed conidiospores.

e. Spores produced from a vegetative mother

Blastospores
cell by budding are called blastospores

Vegetative mother cell

 Sexual reproduction in fungi involves the
fusion of compatible nuclei. Depending on the
species, sexual fusion may occur between haploid
gametes, gamete-producing bodies called
gametangia, or hyphae.

 Sometimes both the cytoplasm and haploid

nuclei fuse immediately to produce the diploid
zygote.

 Usually, however, there is a delay between

cytoplasmic and nuclear fusion. This produces a
dikaryotic stage in which cells contain two
separate haploid nuclei (N N), one from each
parent.
 After a period of dikaryotic existence, the two nuclei fuse and
undergo meiosis to yield spores.

For example,

in the zygomycetes the zygote develops into a zygospore;

in the ascomycetes, an ascospore; and

in the basidomycetes; a basidiospore.

Zygomycetes
Ascomycetes
Basidiomycetes
 Fungal spores are important for several reasons.

 The spores enable fungi to survive environmental stresses such as desiccation,

nutrient limitation, and extreme temperatures, although they are not as stress
resistant as bacterial endospores.

 Because they are often small and light, spores can remain suspended in air for
long periods.

 Fungal spores often spread by adhering to the bodies of insects and other
animals.

 The size, shape, color, and number of spores are useful in the identification of
fungal species.
CULTIVATION OF FUNGI

 Potato Dextrose Media, Sabouraud’s Dextrose media, Rose Bengal

Media medium

 Batch/continuous culture

 Grown under both aerobic and anaerobic conditions

 Long periods (5-50 days)

 Tem 20-40 C
 Colonial Morphology of Fungi

CryptococcuCandida Trichophyto T. menta- Wangiella Aspergillu

s s
albicans n tonsurans grophytes dermatitidi
neoformans s fumigatus
PRESERVATION TECHNIQUES OF FUNGI

 Stock cultures are aseptically transferred at appropriate

intervals to fresh medium and incubated, then stored at 4°C
until they are transferred again

 Many labs use “agar slants;” care has to be taken to avoid

contamination

 Microorganisms require special storage methods in order

to ensure optimal long-term viability and genetic stability.
Preservation method can be assigned to one of the

following groups:

1. Metabolically inactive preservation methods

2. Metabolically active methods

cryocan liquid nitrogen container lyophilizer
 METABOLICALLY INACTIVE PRESERVATION
TECHNIQUES
Advantages: Viable
Cryopreservation
up to 5 year
 Cryopreservation is a process where cells or whole tissues are
preserved by cooling to low sub-zero temperatures, such as −196 °C

Freezing and low temperature storage in or above liquid nitrogen

(-196°C)

 Freezing and low temperature storage below -70°C

Drying

 Preservation by spin freeze-drying

 Preservation by vacuum drying

 Metabolically active preservation
techniques

CryptococcuCandida Trichophyto T. menta- Wangiella Aspergillu

s s
albicans n tonsurans grophytesdermatitidi
neoformans s fumigatus
 FUNGAL TOXINS
Rot disease of Peanut caused
by
Aspergillus niger
Aspergillus niger
 Aflatoxin B1

Aspergillus species

Hepatocellular carcinoma (HCC), or liver cancer, is the third leading cause of

cancer deaths worldwide [World Health Organization (WHO) 2008], with
roughly 5,50,000-6,00,000 new HCC cases globally each year (Ferlay et al.
2004). Aflatoxin exposure in food is a significant risk factor for HCC
(Wild and Gong 2010).
IMPORTANCE OF FUNGI

 Pharmaceuticals- Penicillin, Enzymes

 Agriculture- Bt cotton, Biofertilizer/Biocontrol
(T. viride)
 Baking industry -
 Fermentation- Alcohol
 Pathology- Animals& Plants
 Genetic engineering- Yeast artificial chromosomes
(YACs)
-Yeast two-hybrid system
 ALGAE

• The algae (singular, alga), many of which are unicellular microorganisms.

• These organisms are ubiquitous; many live in aquatic environments but many
also thrive as terrestrial and subterranean algae.

• Algae contain chlorophyll and are photosynthetic.

• They differ from other green plants in having simple reproductive structures
for sexual reproduction.

• They range from microscopic unicellular forms comparable in size to bacteria

to seaweeds that may grow to many feet in length.

• The study of this unique group of organisms is called phycology.

 OCCURRENCE
• They occur in great abundance in the oceans, seas, salt lakes, freshwater lakes, ponds, and streams.

• Many are found in damp soil, on rocks, stones, and tree bark, and on other plants and animals.

• Algae are found where there are sufficient light, moisture, and simple nutrients to sustain them

• Small aquatic forms make up a large part of the free-floating microscopic life in water called plankton, which is the
principal food for aquatic animals, including such large ones as whales.

• (Plankton is generally considered to be composed of both algae and microscopic animal forms.

• Phytoplankton is made up of plants, i.e., algal forms, and zooplankton is composed of animal organisms.
 •- Four types of algae
•
•

Unicellular Colonial Filamentous multicellular

Chlamydomonas • Volvox • Spirogyra • Ulva sp. •

 MORPHOLOGY

• Many species occur as single cells that may be spherical, rod-shaped, club-shaped, or spindle-shaped.

• Others are multicellular and appear in every conceivable form, shape, and degree of complexity, including
membranous colonies, filaments grouped singly or in clusters with individual strands that may be branched
or unbranched, and tubes.

• Algal cells are eucaryotic.

• Cell wall - Thin and rigid.

• The cell walls of many algae are surrounded by a flexible, gelatinous outer matrix secreted through the cell
wall, reminiscent of bacterial capsules.

• As the cells age, the outer matrix often becomes pigmented and stratified.

• Algae contain a discrete nucleus. Other inclusions are starch grains, oil droplets, and vacuoles
 ALGAL PIGMENTS
• The chloroplasts of different divisions of algae containing similar pigments appear to
have similar thylakoid arrangements.
• Chloroplast ultrastructure and pigment chemistry have been used as markers for algal
phylogeny.
• Chlorophylls - There are five chlorophylls; a, b, c, d, and e.
• Carotenoids - There are two kinds of carotenoids: carotenes and xanthophylls. Carotenes
are linear, unsaturated hydrocarbons, and xanthophylls are oxygenated derivatives of
these.
• Biloproteins (Phycobilins) - These are water-soluble pigments, whereas chlorophylls and
carotenoids are lipid-soluble.
• There are two kinds of phycobilins: phycocyanin and phycoerythrin.
• The proportion of one kind of pigment to another can vary considerably with changes in
environmental conditions.
 MOTILITY

• The motile algae, also called the swimming algae, have flagella occurring singly, in pairs, or
in clusters at the anterior or posterior ends of the cell.

• It will suffice for this discussion to mention three types:

• whiplash (cylindrical and smooth);

• tinsel (cylindrical and with hairlike appendages); and

• ribbon, or straplike.

• Some algae have no means of locomotion and are carried about by tides, waves, and
currents.
 REPRODUCTION

• Algae may reproduce either asexually or sexually.

ASEXUAL REPRODUCTION

⁎ Asexual reproductive processes in algae include the purely vegetative type of cell division by which bacteria
reproduce.

⁎ A new algal colony or filament may even start from a fragment of an old multicellular type from which it has
broken.

⁎ However, most asexual reproduction in algae is more complex than this and involves the production of unicellular
spores, many of which, especially in the aquatic forms, have flagella and are motile; these are called zoospores.

⁎ The nonmotile spores, or aplanospores, are more likely to be formed by the terrestrial types of algae. However,
some aplanospores can develop into zoospores.
Sexual reproduction:

⁎ There is a fusion (conjugation) of sex cells, called gametes. to form a union in which "blending" of nuclear
material occurs before new generations are formed.

⁎ The union of gametes forms a zygote.

⁎ If the gametes are "identical," i.e., if there is no visible sex differentiation, the fusion process is isogamous.

⁎ If the two gametes are unlike, differing in size (male and female), the process is heterogamous
Classification of algae
Division Examples

Chlorophyta Chlamydomonas, Volvox

Euglenophyta Euglena

Pyrrophyta Dinophysis (Dinoflagellates)

Chrysophyta Chromulina, Botrydium

Phaeophyta (Brown algae) Sargassum, Ectocarpus

Cyanophyta (Blue Green algae) Nostoc, Anabaena

Rhodophyta (Red algae) Gracillaria,

Economic importance of algae
 PROTOZOA

• Protozoa are unicellular mostly microscopic organisms and are

classified under subkingdom protozoa of the kingdom protista.

• Protozoa are eukaryotic cells having a distinct nucleus as well

as endoplasmic reticulum, golgi apparatus, mitochondria etc. in
the cytoplasm.

• 'Proto' means first and 'zoan' means animals – first animal life
which appear in this universe.

• The flagellates are the most primitive form of animal life and
the ciliates are the most highly organized form of protozoa.

• The study of these eucaryotic protists is called protozoology.

 MORPHOLOGY
Size:
• They have wide variation in size and shape e.g. Leishmania
donovani has a size range of 1-4µm. While ciliates range
about 2000 µm /2mm.
Intracellular structure:
• Like all eukaryotic cells, protozoan cells consists of
cytoplasm separated from the surrounding media by a special
cell envelope.
Cytoplasm:
• cytoplasm is differentiated into endoplasm and ectoplasm.
• The ectoplasm is more gel like and endoplasm is more fluid
like.
• Structures are formal in endoplasm.
• These include endoplasmic reticulum, Golgi complex,
mitochondria, food vacuoles, contractile vacuoles and nuclei.
AMOEBA
Contractile Vacuole:

• Contractile vacuole mainly occur in free living aquatic protozoa.

• They are extremely small rounded floating vacuoles appear in the cytoplasm which coalesce to form
a contractile vacuole having osmoreglatory function and maintain the water balance in the body.

• Food vacuoles are the sites where food particle passes and digestion take place.

• Food vacuole are having the seats of enzymatic activity.

Locomotion:

• They possess different types of locomotory organs. They may bear flagella (flagellates), cilia
(ciliates) or pseudopodia.

• Locomotory organs are absent in the parasitic forms.

Nucleus:

• The protozoan cells have at least one eukaryotic nucleus

however many have multiple nuclei e.g. all ciliates.

• The protozoan nuclei are of various forms sizes and structures.

• In several species each individual organism has two similar

nuclei in ciliates two dissimilar nuclei.

• One large macro nucleus and one small micronucleus.

• Macro nucleus controls metabolic activities and regeneration

process. The micro nucleus is concerned with reproductive PARAMECIUM

activity.
Reproduction:
• Generally protozoa multiply by asexual
reproduction.
• Many are able to carry out both sexual and
asexual reproduction.
• Some parasitic forms may have an asexual
phase in one host and sexual phase in another
host e.g. plasmodium.
Asexual reproduction:
• Asexual reproduction occurs by simple cell
division by binary fission and multiple fission
and budding.
Sexual Reproduction:
• In this fusion of two gametes occur in various
groups of protozoa.
• Conjugation occurs in ciliates.
 Control of Microorganisms
Physical, Chemical and Biological
Methods
Physical Methods
Chemical Agents
Biological Agents
Mode of action
Conditions Influencing Antimicrobial Activity
 Introduction
• The control of microbial growth is necessary in many
practical situations, and significant advances in
agriculture, medicine, and food science have been made
through study of this area of microbiology.
• "Control of microbial growth", as used here, means to
inhibit or prevent growth of microorganisms. The
control of MICROBES in two basic ways:
(1) by killing microorganisms or
(2) by preventing the growth of microorganisms.
• Control of growth usually involves the use of physical
chemical, and biological agents which either kill or
prevent the growth of microorganisms.
 Definitions
• Sterilization: A process that kills all living cells, including
viruses and spores, from a substance or object using
autoclave
• Disinfection: A treatment that reduces the total number
of microbes on an object or surface, but does not
necessarily remove or kill all of the microbes
• Sanitation: Reduction of the microbial population to levels
considered safe by public health standards
• Antiseptic: A mild disinfectant agent suitable for use on
skin surfaces
• -cidal: A suffix meaning that “the agent kills.” For
example, a bacteriocidal agent kills bacteria
• -static: A suffix that means “the agent inhibits growth.”
For example, a fungistatic agent inhibits the growth of
fungi, but doesn’t necessarily kill it.
Physical Methods
• Moist Heat
• Dry Heat
• Low Temperatures
• Filtration
• Radiation
Physical Methods: Moist Heat
• Mechanism of killing is a combination of protein/nucleic
acid denaturation and membrane disruption
• Effectiveness Heavily dependent on type of cells
present as well as environmental conditions (type of
medium or substrate)
• Bacterial spores much more difficult to kill than
vegetative cells
Physical Methods: Moist Heat
• Measurements of killing by moist heat
• Thermal death point (TDP): Lowest temperature at which a
microbial suspension is killed in 10 minutes; misleading
because it implies immediate lethality despite substrate
conditions
• Thermal death time (TDT): Shortest time needed to kill all
organisms in a suspension at a specified temperature under
specific conditions; misleading because it does not account
for the logarithmic nature of the death curve (theoretically
not possible to get down to zero)
Physical Methods: Moist Heat
• Measurements of killing by moist heat (cont.)
• Decimal reduction time (D value): The time required to
reduce a population of microbes by 90% (a 10-fold, or one
decimal, reduction) at a specified temperature and specified
conditions
• z value: The change in temperature, in ºC, necessary to cause
a tenfold change in the D value of an organism under
specified conditions
• F value: The time in minutes at a specific temperature
(usually 121.1°C or 250 °F) needed to kill a population of cells
or spores
Physical Methods: Moist Heat
• Methods of Moist Heat
• Boiling at 100°C
• Effective against most vegetative cells; ineffective against spores;
unsuitable for heat sensitive chemicals & many foods
• Autoclaving/pressure canning
• Temperatures above 100°C achieved by steam pressure
• Most procedures use 121.1°C, achieved at approx. 15 psi pressure,
with 15 - 30 min autoclave time to ensure sterilization
• Sterilization in autoclave in biomedical or clinical laboratory must by
periodically validated by testing with spores of Clostridium or Bacillus
stearothermophilus
Physical Methods: Moist Heat
 Methods of Moist Heat
 Pasteurization is a process of heating a food, which is
usually a liquid, to a specific temperature for a
predefined length of time and then immediately
cooling it after it is removed from the heat. This process
slows spoilage caused by microbial growth in the food.
Pasteurization
Used to reduce microbial numbers in milk and other beverages while
retaining flavor and food quality of the beverage
Retards spoilage but does not sterilize
Traditional treatment of milk, 63°C for 30 min
Flash pasteurization (high-temperature short term pasteurization); quick
heating to about 72°C for 15 sec, then rapid cooling
Physical Methods: Moist Heat
 Physical Methods: Dry Heat
• Incineration
• Burner flames
• Electric loop incinerators
• Air incinerators used with fermenters; generally operated at
500°C
• Oven sterilization
• Used for dry glassware & heat-resistant metal equipment
• Typically 2 hr at 160°C is required to kill bacterial spores by dry
heat: this does not include the time for the glass to reach the
required temp (penetration time) nor does it include the cooling
time
Physical Methods:
Low Temperatures

• Refrigerator:
• around 4°C
• inhibits growth of mesophiles or thermophiles; psychrophiles
will grow
• Freezer:
• “ordinary” freezer around -10 to -20°C
• “ultracold” laboratory freezer typically -80°C
• Generally inhibits all growth; many bacteria and other
microbes may survive freezing temperatures
 Physical Methods: Filtration

• Used for physically removing microbes and dust particles

from solutions and gasses; often used to sterilize heat-
sensitive solutions or to provide a sterilized air flow
• Depth filters: eg. Diatomaceous earth, unglazed porcelean
• Membrane filters: eg. Nitrocellulose, nylon, polyvinylidene
difluoride
• HEPA filters: High efficiency particulate air filters used in
laminar flow biological safety cabinets
Physical Methods: Radiation
• Ultraviolet Radiation
• DNA absorbs ultraviolet radiation at 260 nm
wavelength
• This causes damage to DNA in the form of thymine
dimer mutations
• Useful for continuous disinfection of work surfaces, e.g.
in biological safety cabinets
Physical Methods: Radiation
• Ionizing Radiation
• Gamma radiation produced by Cobalt-60 source
• Powerful sterilizing agent; penetrates and damages both
DNA and protein; effective against both vegetative cells and
spores
• Often used for sterilizing disposable plastic labware, e.g.
petri dishes; as well as antibiotics, hormones, sutures, and
other heat-sensitive materials
• Also can be used for sterilization of food; has been approved
but has not been widely adopted by the food industry
Chemical Agents
• Phenolics
• Alcohols
• Halogens
• Heavy metals
• Quaternary Ammonium Compounds
• Aldehydes
• Peptides
Phenolics
• phenol and phenolics (phenol derivatives) such as cresols, xylenols,
and orthophenylphenol - disinfectants in laboratories and hospitals.
• Phenolics act by denaturing proteins and disrupting cell membranes.
• advantages as disinfectants:
• phenolics are tuberculocidal, effective in the presence of organic
material, and remain active on surfaces long after application.
• have a disagreeable odor and can cause skin irritation.
Alcohols
• most widely used disinfectants and antiseptics.
• They are bactericidal and fungicidal but not sporicidal; some lipid-
containing viruses are also destroyed.
• The two most popular alcohol germicides are ethanol and
isopropanol, usually used in about 70 to 80% concentration.
• denaturing proteins and possibly by dissolving membrane lipids.
• A 10 to 15 minute soaking is sufficient to disinfect thermometers and
small instruments.
Halogens
• fluorine, chlorine, bromine, iodine, and astatine
• The halogens iodine and chlorine are important antimicrobial agents.
• used as a skin antiseptic and kills by oxidizing cell constituents and iodinating cell
proteins.
• At higher concentrations- even kill some spores.
• Iodine - tincture of iodine, 2% or more iodine in a water-ethanol solution of
potassium iodide.
• Iodophor-release iodine slowly to minimize skin burns and irritation.
• used in hospitals for preoperative skin degerming and disinfecting.
Heavy Metals
• mercury, silver, arsenic, zinc, and copper - used as germicides.
• 1% solution of silver nitrate is often added to the eyes of infants to prevent
ophthalmic gonorrhea (in many hospitals, erythromycin is used instead of
silver nitrate because it is effective against Chlamydia as well as Neisseria).
• Silver sulfadiazine is used on burns.
• Copper sulfate is an effective algicide in lakes and swimming pools.
• Heavy metals combine with proteins, often with their
sulfhydryl groups, and inactivate them. They may also
precipitate cell proteins.
Quaternary Ammonium Compounds
• Anionic, non-ionic and cationic
• cationic detergents are effective disinfectants.
• The most popular of these disinfectants are quaternary ammonium
compounds characterized by a positively charged quaternary
nitrogen and a long hydrophobic aliphatic chain
• They disrupt microbial membranes and may also denature proteins.
• Eg.: benzalkonium chloride and cetylpyridinium chloride
Aldehydes
• aldehydes, formaldehyde and glutaraldehyde - are highly reactive
molecules
• that combine with nucleic acids and proteins and inactivate them,
probably by crosslinking and alkylating molecules
• They are sporicidal and can be used as chemical sterilants.
• Glutaraldehyde is less irritating than formaldehyde - used to
disinfect hospital and laboratory equipment.
• Sterilizing gases
• Many heat-sensitive items such as plastic Petri dishes, heart-lung machine
components, sutures, and catheters are sterilized with ethylene oxide gas. Ethylene oxide
(EtO) is both microbicidal and sporicidal.
• It is a strong alkylating agent that kills by reacting with DNA and proteins to block
replication and enzymatic activity.
• It is a particularly effective sterilizing agent because it rapidly penetrates packing
materials, even plastic wraps.
• Chlorine dioxide (ClO2) gas is also used as a disinfectant. It has been used to sterilize
hospital operating and patient rooms.
• ClO2 fumigation is used in the food industry to sanitize fruits and vegetables of
contaminating yeasts and molds.
• Vaporized hydrogen peroxide (VHP) can also be used to decontaminate biological safety
cabinets, operating rooms, and other large facilities.
• During the course of the decontamination process, VHP breaks down into water and
oxygen, both of which are harmless.
 Antibiotics
• Antibiotics are generally considered to be organic
compounds of low molecular weight produced by
microbes.
• At low concentration, antibiotics are deleterious to the
growth or other metabolic activities of other
microorganisms.
 Most of the Antibiotics produced by
Microorganisms

Antibiotic Producing microorganism

Cephalosporin Cephalosporium acrimonium
Chloramphenicol Streptomyces venezuelae
Erythromycin Streptomyces erythreus
Griseofulvin Penicillium griseofulvin
Penicillin Penicillium chrysogenum
Streptomycin Streptomyces griseus
Tetracycline Streptomyces aureofaciens
Gentamicin Micromonospora purpurea
 Penicillin
• All penicillin like antibiotics inhibit synthesis of peptidoglycan, an
essential part of the cell wall.
• They do not interfere with the synthesis of other intracellular
components.
• These antibiotics do not affect human cells because human cells do
not have cell walls.
• Penicillins are active against Gram positive bacteria
• Some members (e.g. amoxicillin) are also effective against
Gram negative bacteria
PRODUCTION OF PENICILLIN
• Penicillin was the first important commercial product produced
by an aerobic, submerged fermentation
• First antibiotic to have been manufacture in bulk.
• Used as input material for some semi synthetic antibiotics.
• It is fermented in a batch culture
 Thanks to work by Alexander Fleming (1881-1955), Howard
Florey ( 1898-1968) and Ernst Chain (1906-1979), penicillin
was first produced on a large scale for human use in 1943. At
this time, the development of a pill that could reliably kill

 bacteria was a remarkable development and many lives were

saved during World War II because this medication was
available.

A. Fleming E. Chain H. Florey

 A tale by A. Fleming
• In 1928, Sir Alexander Fleming, a Scottish biologist,
observed that Penicillium notatum,
• a common mold, had destroyed staphylococcus
bacteria in culture.

He published a report on penicillin and its

potential uses in the British Journal of
Experimental Pathology.
Penicillin
Mechanism of Antibiotics
Summary of antimicrobial agents affecting cell wall
synthesis
Agents affecting
the cell wall b-lactamase
inhibitors
b-lactam antibiotics Clavulanic acid
Other antibiotics Sulbactam
Bacitracin Tazobactam
Vancomycin
Daptomycin

Penicillins Cephalosporins Carbapenems Monobactams

Amoxicillin Ertapenem
Imipenem/cilastatin* Aztreonam
Ampicillin Meropenem
Dicloxacillin
Indanyl carbenicillin
Methicillin 1st generation 2nd generation 3rd generation 4th generation
Nafcillin Cefadroxil Cefaclor Cefdinir Cefepime
Oxacillin Cefazolin Cefprozil
Penicillin G Cefixime
Cephalexin Cefuroxime Cefotaxime
Penicillin V Cefoxitin Ceftazidime
Piperacillin Ceftibuten
Ticarcillin Ceftizoxime
Ceftriaxone

(according to Lippincott´s Pharmacology, 2009)

 Peptidoglycan Synthesis

“Penicillin binding
protein”
P. aeruginosa treated with Rifampin
• propidium iodide ------ viable cells counting
• ethidium bromide ----- dead cells counting

Control (without Anti) 5 µg/mL, 30 min 25 µg/mL, 30 min

Summary of antimicrobial agents affecting cell wall
synthesis
Agents affecting
the cell wall b-lactamase
inhibitors
b-lactam antibiotics Other antibiotics Clavulanic acid
Sulbactam
Bacitracin Tazobactam
Vancomycin
Daptomycin

Penicillins Cephalosporins Carbapenems Monobactams

Amoxicillin Ertapenem
Imipenem/cilastatin* Aztreonam
Ampicillin Meropenem
Dicloxacillin
Indanyl carbenicillin 1st generation 2nd generation
Methicillin 3rd generation 4th generation
Nafcillin Cefadroxil Cefaclor Cefepime
Oxacillin Cefdinir
Cefazolin Cefprozil Cefixime
Penicillin G Cephalexin Cefuroxime Cefotaxime
Penicillin V Cefoxitin Ceftazidime
Piperacillin Ceftibuten
Ticarcillin Ceftizoxime
Ceftriaxone
The Beta-Lactam Antibiotics

• Cell wall active agents

• Prevent the final step in the
synthesis of the bacterial cell wall

• Range from very narrow spectrum

to very broad spectrum β-lactam ring
How do they work?
1. The β-lactam binds to Penicillin Binding Protein (PBP)
2. PBP is unable to crosslink peptidoglycan chains
3. The bacteria is unable to synthesize a stable cell wall
4. The bacteria is lysed (cidal effects). bacteriacidal effect against
G+&G-
Penicillin-β lactum antibiotic
Cephalosporin
• The cephalosporins are a class of β-lactam antibiotics originally
derived from the fungus Acremonium, which was previously known as
"Cephalosporium".
• Cephamycins constitute a subgroup of β-lactam antibiotics called
cephems.
• A lactam is a cyclic amide. The term is a lactone + amide.

β-lactam 108
Mode of action - Cephalosporins
• Cephalosporins are bactericidal and have the same mode of
action as other β-lactam antibiotics (such as penicillins), but are
less susceptible to β-lactamases.
• Cephalosporins disrupt the synthesis of the peptidoglycan layer
of bacterial cell walls.
• The final transpeptidation step in the synthesis of the
peptidoglycan is facilitated by transpeptidases known as
penicillin-binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala
at the end of muropeptides (peptidoglycan precursors) to
crosslink the peptidoglycan.
• Active against both Gram positive and negative bacteria
 Peptidoglycan Synthesis

“Penicillin
binding protein”
Conditions Influencing Antimicrobial Activity
• Several critical factors play key roles in determining the
effectiveness of an antimicrobial agent, including:
• Population size
• Types of organisms
• Concentration of the antimicrobial agent
• Duration of exposure
• Temperature
• pH
• Organic matter
Broad spectrum antibiotics-Antibiotics
from procaryotes
 Most of the Antibiotics produced by
Microorganisms

Antibiotic Producing microorganism

Cephalosporin Cephalosporium acrimonium
Chloramphenicol Streptomyces venezuelae
Erythromycin Streptomyces erythreus
Griseofulvin Penicillium griseofulvin
Penicillin Penicillium chrysogenum
Streptomycin Streptomyces griseus
Tetracycline Streptomyces aureofaciens
Gentamicin Micromonospora purpurea
 ANTIBIOTICS

 Classification according chemical structure similarity

 I. ß-Lactam antibiotcs
 II . The Aminoglycoside Antibiotics
 III . The Macrolide Antibiotics
 IV : Antibiotics with fused ring systems:
 V. Lincomycins
 VII .Polypeptide Antibiotics
 VIII.Unclassified antibiotics
A. Penicillin
• Natural penicillin
• Penicillin G; benzylpenicillin
• ß-Lactam thiazolidine penam penicillin penicillanic acid
 • Ampicillin
• 6-[D-a-Aminophenylacetamido] penicillanic acid; 6--amino-
benzyl penicillin

Amoxicillin, 6-[D-(-)--Amino-p-hydroxy-phenylacetamido]
penicillanic acid
(Amoxil).

The incorporation of an acidic substiuent at the α-benzyl carbon

atom of penicillin G also imparts clinical effectiveness against Gram-
negative bacilli and, furthermore, extends the spectrum of activity to
include organisms that are resistant to ampicillin .
Mode of action of penicillin

• Inhibit cell wall synthesis by acylation of transpeptidase enzyme

necessary for synthesis of dipeptidogycan which responsible for
rigidity and strength of the cell wall
 ß-Lactamase inhibitors
Clavulanate Potassium:
• Clavulanic acid is an antibiotic isolated from Streptomyces clavuligeris.
Structurally it is 1-oxapenam lacking the 6-acylamino side chain of
penicillin, but possessing a 2-hydroxyethylidene moiety at C-2.
Sulbactam
• This synthetic penicillin derivative is a potent inhibitor of ß-
lactamase. It potentiates the activity of ampicillin and carbenicillin
against ß -lactamase producing bacteria.
• Combinations of amoxicillin and the potassium salt of clavulanic acid
are available (Augmentin) in a variety of fixed-dose, oral dosage forms
intended for the treatment of skin, respiratory, ear and urinary tract
infections caused by ß-lactamase producing bacterial strains resistant to
amoxicillin alone.

119
 B- Cephalosporins:
Cephalosporins are ß-lactam antibiotics isolated
from Cephalosporium species or prepared
semisynthetically
Semisynthetic Derivatives:
In the preparation of semisynthetic cephalosporins, the
following
improvements are sought:
(1) increased acid stability;
(2) improved pharmacokinetic properties, particularly better oral
absorption;
(3) broadened antimicrobial spectrum;
(4) increased activity against resistant microorganisms
(5) decreased allergenicity; and
(6) increased tolerance after parenteral administration
Cephradine, USP (Velosef)
Available oral and parentral

Cefadroxil, USP (Duricef )

Slowly excreted , longer duration HO
of action O
H H
S
N
H • H2 O
NH 2 N
O CH 3

COOH
Cafaclor USP (Ceclor)
More potent against Hemophiles
influenza
 II . Aminoglycoside Antibiotics
• Aminologlycosides are so named because their structures
consist of amino sugars linked glycosidically.
• The streptomycin, neomycin, paromomycins, gentamicins,
Tobramycins, Kanamycins, and Amikacins have many chemical and
antimicrobial features in common:
• All these antibiotics show broad spectrum antimicrobial activity
• Paromomycin inhibits Enatmoeba histolytica.
• neomycin - used widely in the treatment of intestinal infections
and chemosterilization of the bowel prior to surgery of that organ
Mechanism of Action

• The amino glycosides

- act directly on the bacterial ribosome to inhibit the initiation
of protein synthesis
- and to interfere with the fidelity of translation of the genetic
message.
• They bind to the 30S ribosomal subunit to form a complex that is
unable to initiate proper amino acid polymerization
 III . Macrolide Antibiotics
• Macrolides are a group of macrocyclic antibiotics containing:
An amino sugar linked glycosidically to the lactone ring,
A neutral sugar linked to the ring or the basic sugar and contains a
ketone group.

• The macrolides are principally active against Gram positive

bacteria and show useful activity against penicillin-resistant
strains.
• Also exhibit effectiveness against gram-negative cocci.
• Mode of action: Bacteriostatic, bind to 50S ribosomal subunit to
prevent the translocation step of bacterial protein synthesis
• Eg: Erythrommycin, Azithromycin

124
 IV : Antibiotics with fused ring systems:
The group includes the broad-spectrum tetracycline.
• The Tetracycline
• Comprises a group of antibiotics characterized by their
common octahydronaphthacene skeleton.

Name R1 R2 R3 R4 Other names

a. Tetracycline H OH CH3 H Achromycin
b. 7-Chlortetracyclin H OH CH3 Cl oxycycline
c. 5-Oxytetracyclin OH OH CH3 H Terramycin
d.6-Demethyl-7-chloro tetracyclin H OH H Cl Demeclocycl
e 6-Demethy1-6-deoxy-5-hydroxy-6- OH CH2 = H Methacyclin
methylene tetracycline e
f. 6-Deoxy-5-oxytetracycline OH H CH3 H Doxycycline
g. 7-Dimethylamino 6-demethyl-6- H H H N(CH3)2 Minocycline
deoxytetracycline
V. Lincomycins
• They are known as Sulphur containing Antibiotics
• Mode of action: act via 50S ribosomal subunit binding & protein
synthesis inhibition.
• They are used in extra CNS anaerobic infections, Penicillin
sensitive patients

CLINDAMYCIN
LINCOMYCIN 7S-Cloro-7S-deoxylincomycin
semisynthetic
 VI.Polypeptide Antibiotics
• The most powerful antibiotic agents but limited for renal toxicity.
• Used mainly locally in burns.
• Mode of action: Inhibit mucopeptide cell wall synthesis and
interfere with semipermeability of cell membrane

BACITRACIN
GRAMICIDIN

Val–Orn–Leu– D -Phe–Pro

Pro– D -Phe–Leu–Orn–Val

POLYMYXIN (B)
127
VII. Unclassified Antibiotics
• CHLORAMPHENICOL
• In meningitis, typhoid & paratyphoid fever.

D-(-) threo-2-Dichloroacetamido --1-(4–

nitrophenyl)-1,3-propanediol

Thiamphenicol CH3SO2-
 Antimicrobial Drug Resistance Is a Public Health Threat

• The spread of antibiotic-resistant bacteria has become so widespread that methicillin-

resistant S. aureus (MRSA) has become well known.
• Fortunately, most MRSA strains can still be treated, but the more recent emergence of
vancomycin-resistant enterococci (VRE) and carbapenem-resistant Enterobacteriaceae
(CRE) bacteria has caused great concern among public health officials worldwide.
• There are two types of resistance: intrinsic and acquired.
• An example of intrinsic resistance is that of mycoplasma resistance to β-lactam antibiotics
and other cell wall inhibitors simply because these bacteria lack a cell wall.
• Acquired resistance occurs when there is a change in the genome of a bacterium that
converts it from one that is sensitive to an antibiotic to one that is resistant.
 MECHANISMS FOR ACQUIRING
RESISTANCE

• Bacteria use several mechanisms to

become antibiotic-resistant:
• Inactivation of the antibiotic
• Efflux pumping of the antibiotic
• Modification of the antibiotic target
• Alteration of the pathway
INACTIVATION OF ANTIBIOTIC
• Inactivation involves enzymatic breakdown of
antibiotic molecules.
• A good example is β-lactamase:
• Secreted into the bacterial periplasmic space
• Attacks the antibiotic as it approaches its target
• There are more than 190 forms of β-lactamase.
• E.g of lactamase activity in E.coli and S. aureus
MECHANISMS FOR
ACQUIRING RESISTANCE
Destruction of normal flora allows
pathogenic pathogens to dominate
 MRSA, VRSA, VRE, AND OTHER
PATHOGENS
 Several antibiotic-resistant bacteria are considered
clinically dangerous.
› MRSA (Methicillin-Resistant) and VRSA (Vancomycin-
resitant S.aureus are very virulent in humans and are referred as
professional pathogens.
 MRSA and VRSA contain many resistance genes.
› Three or four resistance islands on the chromosome
› 26-28 additional gene clusters on plasmids which can move to
other bacterial cells.
› VRE-Vancomycin enterococcus e.g E. faecalis contributes to 90%
of all vancomycin resistant bacteria
• Clostridium difficile is a superinfection pathogen.
• Establishes itself in the intestinal tract as part of a superinfection
• It is very resistant to antibiotics.
• Patients with this infection are difficult to treat
Guidelines for extending the useful life of
antimicrobial drugs
Antifungal agents
 Antifungal agents
• Human fungal infections have increased dramatically in recent
years
• Fungal infections are usually more difficult to treat than
bacterial infections, because fungal organisms grow slowly
- because fungal infections often occur in tissues
that are poorly penetrated by antimicrobial agents
• Therapy of fungal infections usually requires prolonged
treatment.
• They are complex organisms in comparison to
bacteria.Thus antibacterial agents are not effective
against fungi.
• Fungal infections are also called as mycoses
• They have nucleus and well defined nuclear
membrane, and chromosomes.
• they have rigid cell wall composed of chitin (N –
acetylglucosamine )
where as bacterial cell wall is composed of
peptidoglycan

• fungal cell membrane contains ergosterol , human

cell membrane is composed of cholesterol
Fungal infections
• SUPERFECIAL
• Dermatomycoses affecting skin, hair or nails.
• Epidermophyton (skin and nails)
• Trichophyton (skin,hair & nail)
• Microsporum (skin and hair)

• b) Candidiasis (commonly normal flora of mouth, skin, intestines

and vagina) infection caused by genus Candida affecting skin,
mucous membrane of mouth or G.I.T or female genital tract
• SYSTEMIC
Candidiasis ,Cryptococosis, Aspergillosis,
Blastomycosis, Histoplasmosis,
Coccidioidomycosis, Paracoccidioidomycosis etc.
Drug Classification
• A) Drugs that disrupt
fungal cell membrane
b) Triazole
• i) Polyenes Fluconazole
Itraconazole
Tioconazole
Amphotericin iii) Allylamines
Nystatin Terbinafine
Natamycin
Naftifine
• ii) Azoles Butenafine
a) Imidazole iv) Echinocandins
caspofungin,
Ketoconazole
Butaxonazole
Clotrimazole
Econazole
Miconazole
Oxiconazole
Sulconazole
Drug classification cot’d

B) Drugs that inhibits mitosis

Griseofulvin

C) Drugs that inhibits DNA synthesis

flucytosine

D) Miscellaneous
Haloprogi
Tolnaftate
Whitefield's ointment
Ciclopirox olamine
Mechanism of action of different anti fungal drugs
 Uses of antifungal drugs
Disease Drug used
Systemic infections
 systemic candidiasis  Amphotericin, flucytocin, , fluconazole.

 Cryptococcosis( meningitis)  Amphotericin, flucytocin , fluconazole,

itraconazole
 systemic aspergillosis  itraconazole Amphotericin,

 Blastomycosis  itraconazole Amphotericin,

 Histoplasmosis Amphotericin, itraconazole ,fluconazole.

 Coccidiomycosis  fluconazole. itraconazole ,Amphotericin,

 Paracoccidiomycosis  fluconazole. itraconazole ,Amphotericin,

 Mucormycosis  Amphotericin, flucytocin ,Amphotericin,

 Disseminated sportrichosis  Amphotericin, flucytocin
Antiviral Drugs

145
 Antiviral Drugs
• Vaccines are often used to build up immunity
before a viral infection occurs.

• Common viral infections such as the influenza,

mumps, or chicken pox are usually overcome
by the body’s immune system.

• To be effective, antiviral agents must either

block viral entry into or exit from the cell or be
active inside the host cell.

146
• Antiviral drugs work by:

1.Altering the cell’s genetic material so that the

virus cannot use it to multiply, i.e. acyclovir
(inhibiting Viral enzymes, Host expression of viral
proteins & Assembly of viral proteins)

2.Preventing new virus formed from leaving the

cell, i.e. amatadine.
• Antiviral therapy challenging.
1. Rapid replication of viruses makes it
difficult to develop effective antiviral.
2. Viruses can rapidly mutate and drug becomes
ineffective.
3. Difficulty for drug to find virus without injuring
normal cells.(Nonselective inhibitors of virus
replication may interfere with host cell function and
result in toxicity.)

Antiviral drugs share the common property of

being virustatic; they are active only
against replicating viruses and do not affect
latent virus.
148
 Agents To Treat
Herpes Simplex Virus (HSV)
& Varicella-zoster Virus (VZV)
Infections
Oral Agents Topical Agents
Acyclovir Acyclovir
Valacyclovir Docosanol
Famciclovir Penciclovir

Ophthalmic Intravenous
Trifluridine Acyclovir
• Herpes simplex viruses (HSV)—cause
repeated, blister-like lesions on the skin,
genitals, mucosal surfaces.

• Some remain latent; activated by physical

or emotional stress
• HSV-type 1—non genital

• HSV type 2—genital infections

Acyclovir
• Valacyclovir is a prodrug, Acyclovir
with better availability Herpes virus
specific
• Acyclovir is Guanosine thymidine kinase

analog Acyclovir
monophosphate
• mostly taken up by the
virus infected cells and Host kinase
has low toxicity for host Acyclovir
cells. triphosphate

1. Incorporated into DNA and terminates synthesis

2. Inhibition of herpes virus DNA polymerase
Acyclovir.
Clinical Use
• Herpes simplex
• Herpes zoster
• Chickenpox
• Epstain-Barr virus
 Ganciclovir
Valganciclovir ( a prodrug)

• Mechanism like Acyclovir

• Active against all Herpes viruses & CMV
• Low oral bioavailability given I.V.
• Most common A/E: bone marrow suppression
(leukopenia, thrombocytopenia ) and CNS effects
(headache, psychosis, convulsions).
• 1/3 of patients have to stop because of adverse
effects
 Foscarnet
• An inorganic pyrophosphate analog
• does not have to be phosphorylated
• Active against Herpes (I, II, Varicella , CMV),
including those resistant to Acyclovir and
Ganciclovir.
• IV only
• MOA:Direct inhibition of DNA polymerase and RT
• Foscarnet should only be given during
pregnancy when benefit outweighs risk.
Cidofovir

• Incorporation into viral DNA chain results in

reductions of the rate of viral DNA synthesis

• Must be administered with high-dose

probenecid & adequate hydration
Antiretroviral Agents
• Retroviruses are enveloped, single stranded RNA
viruses that replicate through a DNA intermediate
using Reverse Transcriptase.

• This enzyme converts the RNA genome into DNA,

which then integrates into the host chromosomal
DNA by the enzyme Integrase.

• This large and diverse family includes members

that are oncogenic, are associated with a variety
of immune system disorders, and cause
degenerative and neurological syndromes.
Current classes of antiretroviral drugs
include:
Three main enzymatic targets:
 Reverse Transcriptase
 Protease
 Integrase

six drug classes

1. Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

2. Non Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

3. Protease inhibitors (PIs)

4. Entery inhibitors

5. CCR5 receptor antagonists

6. Integrase inhibitors
Lantibiotics
 Lantibiotics
spread of bacterial resistance leads to a
growing demand for novel antibiotics

Bacteriocins

Amino acid sequence and bridging pattern of selected

•

representatives of type A and type B lantibiotics.

•Type A lantibiotics kill bacteria by forming pores in the cytoplasmic

membrane
• type B lantibiotics depicted inhibit cell wall biosynthesis.
Nisin is an antimicrobial peptide produced by certain Lactococcus
species.
Nisin has been accepted as a safe and natural preservative for
milk and other food products in more than 50 countries
This peptide inhibits the vegetative growth of a range of gram-
positive bacteria
nisin inhibits the food-borne pathogens Listeria monocytogenes,
Staphylococcus aureus, and psychrotrophic enterotoxigenic
Bacillus cereus, the effectiveness of nisin as a food preservative
against these organisms under various preservation conditions
Bacteriocins are toxins produced by bacteria directed at killing a
limited number of close relatives.