Atypical bacteria

(Non gram staining/poorly staining

bacteria)
Mycobacteria
Mycoplasma
Chlamydia
 Typical vs. atypical bacteria
• Atypical bacteria include groups of organisms that
lack significant characteristic structural components
or metabolic capabilities that distinguish them from
the larger group of typical bacteria.
• Typical bacteria have shapes that can be described
as a rod, coccus or corkscrew/spirochete etc
• Nearly all bacteria, except mycoplasma, have a rigid
cell wall surrounding the cell membrane that
determines their shape.
• Also include non-gram-staining/ poorly staining
bacteria
 Atypical bacteria

– Mycobacteria;
– Chlamydiae;
– Mycoplasma
– Rickettsiae
 Mycobacteria
• Strictly aerobic, acid fast, non spore forming
rods
• Non motile
• Do not stain well (Gram stain indeterminate)
due to high lipid content of their cell wall (60%
lipid)
• High lipid content makes mycobacteria
strongly hydrophobic and acid fast i.e. they
stain poorly but, once stained, cannot be
easily decolorized by treatment with acidified
organic solvents.
 Classification of mycobacteria
• Mycobacteria can be divided into two main
groups on the basis of their growth rates in vitro;
– Fast/Rapidly-growing mycobacteria -readily
visible colonies on solid growth media within
7 days
– Slow-growing mycobacteria- Require longer
than 7 days to produce readily visible colonies on
solid media.
– Slow growing bacteria that are the common cause of
disease in humans include; M.Tuberculosis complex,
M.leprae and M.avium complex
 Tuberculous and Non-Tuberculous
Mycobacteria
• Tuberculous mycobacteria (those that cause tuberculosis
and leprosy)
– Mycobacterium tuberculosis complex (cause
Tuberculosis) which includes;
• Mycobacterium tuberculosis
• M.bovis
• M.africanum
• M.microti
• M.canetti
NB; Not all have been found to cause disease in
humans
– Mycobacterium leprae
 Tuberculous and Non-Tuberculous
Mycobacteria
• Non-tuberculous mycobacteria (NTM);
– Also known as environmental mycobacteria.
Examples include
• M.abscessus
• M.avium
• M.fortuitum
• M.intracellulare
• M.smegmatis
• M.haemophilum
Etc.
 Mycobacterium tuberculosis
• Discovered by Robert Koch in 1882 as the
causative agent of human tuberculosis.
– Rod shaped
– Acid fast
– Aflagellate therefore non-motile
– Slow-growing
– Capacity for ‘dormancy’
– Obligate aerobe
– Lacks most of the classical bacterial virulence
factors
 Epidemiology
• Estimated that about one third of the world’s
population is infected with M. tuberculosis
(MTB), with 30 million people having active
disease
• Patients with active pulmonary disease spread
MTB through respiratory droplets while
coughing
• Because of resistance to dessication, the
organisms can remain viable as droplet nuclei
suspended in room air for at least 30 minutes
 Pathogenesis
• Infection occurs when droplet nuclei containing MTB are inhaled
and reach the alveoli of the lungs.
• Organisms are ingested by alveolar macrophages; majority of
which are killed/inhibited.
• Although the organism produces no demonstrable toxins, when
engulfed by macrophages, bacterial sulfolipids inhibit the fusion
of phagocytic vesicles with lysosomes.
• A small number multiply intracellularly and spread via blood to
extrapulmonary sites e.g. the brain, lymph nodes, bones and
kidney
• Virulence of MTB depends on its ability to survive and grow within
host cells(evade immune clearance).
• MTB can remain viable within host cells for decades (latency)
 Clinical disease
• Primary TB; Occurs in person who hasn’t had
previous exposure to the organism. Active
disease from primary infection is a rare event,
occurring mostly in young children and the
elderly. Also seen in immunosuppressed
• Majority of cases (approx. 95%) of primary TB
are arrested by the cell mediated immune
system.
• Latent TB infection (LTBI); Persons with LTBI
have M.tuberculosis in their bodies but do not
have TB disease, and cannot spread infection
to other people.
 Clinical disease
• TB disease reactivation; Usually caused by MTB that
has survived in a dormant primary tubercle lesion
(commonly in a pulmonary site-particularly the lung
apices where high oxygen tension favors
mycobacterial growth, although can be
extrapulmonary)
• The patient again becomes capable of exposing
others to the disease(unless disease is
extrapulmonary)
• Risk factors for reactivation are associated with
impairment in immune status due to for example;
– Malnutrition, alcoholism, advanced age, underlying
health conditions (particularly HIV, diabetes)
 Presentation of active TB infection
 Pulmonary/cavitary  Extrapulmonary/miliary
TB TB (disseminated TB)
• Cough +/- • Fever of unknown origin
haemoptysis (blood) • Pulmonary involvement
• Chest pain • Renal disease
• Weight loss • Clotting abnormalities
• Cardiac involvement
• Fatigue
(pericarditis,
• Fever/night sweats endocarditis)
• Malaise • Osteomyelitis
• Tuberculous meningitis
• Cavitary TB; Upper lobes of lungs are most
affected
• Miliary TB usually occurs shortly after primary
infection; ‘Miliary’ describes the appearance on
chest x-ray of very small nodules throughout the
lungs that look like millet seed. These tubercular
foci can be distributed in vital organs all over the
body as the bacteria spread via an eroded blood
vessel and the patient becomes acutely ill. Fever of
unknown origin common
• Other forms; laryngeal TB
 Diagnosis
• Demonstration of
clinical symptoms
• Chest X-ray for
abnormality
• Ziehl-Neelsen/acid-
fast staining of
clinical specimens
(MTB is however not
morphologically
distinguishable from
other members of
the genus.
 Diagnosis
• Definitive diagnosis can be obtained by
culturing the organism(can require anywhere
from 2 to 8weeks as MTB is slow growing)
– Culture may also be useful for determining
antibiotic sensitivity
• Nucleic acid based test also provides definitive
diagnosis and shorten time required to detect
MTB.
– PCR
– Genetic probes (hybridization)
 Treatment
• Patients with drug-susceptible TB
 Intensive phase; Isoniazid, Rifampicin,
Pyrazinamide, Ethambutol for 2months (“first-
line” drugs)
Plus
 Continuation phase; Isoniazid and Rifampicin for
4months
• Patients with multi drug resistant TB (MDR)
(resistant to Isoniazid and Rifampicin) or
Extensively drug resistant TB(XDR) may require
up to 24months of treatment
 Treatment
• Clinical tuberculosis requires a long course of
treatment because of the characteristics of
the organisms and the lesions they produce
– As intracellular pathogens, they are shielded from
drugs that do not penetrate host cells
– large cavities with avascular centres (lacking blood
supply) are penetrated by drugs with difficulty.
– In chronic or arrested tubercles, the organisms are
non-proliferating and, therefore, not susceptible
to many antimicrobial agents.
 Prevention
– BCG vaccine; 70-80% protective against the more
severe forms of TB e.g. TB meningitis in children. It
is less effective in preventing pulmonary TB which
is the more common form of TB in adults
– Public health measures; tuberculin tests, chest
radiographs, case registries and contact tracing for
control at the population level
– Latent disease chemotherapy -usually with single
antibiotic, Isoniazid. Exclude active disease before
giving treatment
 Mycobacterium leprae
• Cause of Leprosy(Hansen’s disease)
• Mostly found in warm tropical countries. Very
uncommon in developed countries
• M.leprae is transmitted from human to human
through prolonged contact, e.g., between exudates
of a leprosy patient’s skin lesions and the abraded
skin of another individual or nasal droplet infection
• Estimated 10-12million cases worldwide
• Infectivity of M.leprae is low, and the incubation
period protracted, so that clinical disease may
develop years or even decades after initial contact
with the organism.
 Clinical significance of M.leprae
Leprosy is a chronic condition of peripheral
nerves and mucocutaneous tissues. Disease is in
one of two clinical forms;
• Tuberculoid/paucibacillary
leprosy
– Characterised by
hypopigmented
macules(flattened wide spots)
on cooler body tissues such as
skin (especially the nose,
outer ears and testis)
– Neuritis leads to anaesthetic
patches (insensitive to pain)
on the skin
 Clinical significance of M.leprae
• Lepromatous/multiba
cillary leprosy
– Raised skin
lesions/nodules
– Thickened dermis
– Nasal congestion and
bleeds
– Hypoesthsia;
decreased sensitivity to
touch, temperature OR
– Hyperesthesia;
Increased sensitivity
 Diagnosis and treatment
Diagnosis Treatment
• Not culturable in artificial • LL; rifampicin+
culture. dapsone
• Acid fast staining (6months)
– Lepromatous leprosy (LL); • TL; rifampicin+
specimens from nasal
mucosa and other infected
dapsone+
areas can demonstrate clofazimine
organism (24months)
– Tuberculoid leprosy(TL);
organisms are extremely
rare. Diagnosis depends on
clinical findings and histology
of biopsy material
 Mycobacterium avian complex
• Most common cause of non-tuberculous
pulmonary infections
• Manifest as;
– chronic bronchitis
– chronic obstructive pulmonary disease
• Associated with disseminated infections in
HIV/AIDS patients
• Not susceptible to some standard TB drugs
 Mycoplasma
Mycoplasma are small prokaryotic organisms
that lack the rigid cell wall that most other
bacteria possess.
• They are therefore pleomorphic (take on
various shapes)and cannot be classified as
either cocci or rods.
• Only enclosed by a plasma membrane which is
essentially a lipid bilayer.
• Widely distributed in nature and include several
commensals commonly found in the mouth and
urogenital tracts of humans and other
mammals.
Structural features
 Significance
• Mycoplasma pneumoniae most medically
significant-cause of atypical pneumonia.
– The organism accounts for about 20% of
pneumoniae cases
• Other pathogenic mycoplasmas; Mycoplasma
hominis, Ureaplasma urealyticum
– associated with a variety of urogenital diseases, such
as urethritis, pelvic inflammatory disease (PID), and
intra- partum infections.
• Mycoplasma genitalium; recently recognized
sexually transmitted pathogen that causes non-
gonococcal urethritis.
 Chlamydiae
• Chlamydiae small, round-to-ovoid organisms
that vary in size during the different stages of
their reproductive cycle.
• Chlamydia bear similarities with gram negative
bacteria, with an envelope consisting of two
lipid bilayers resembling a gram-negative
envelope.
• Peptidoglycan has not been demonstrated in
Chlamydiae.
• They are obligate intracellular parasites
• The most important human pathogen is
Chlamydia trachomatis.
 Life cycle and pathogenesis
• Chlamydiae have a unique life cycle with
morphologically distinct infectious and
reproductive forms.
• The infectious form is called the elementary
body which is a dormant structure that can
survive extracellularly and pass from cell to
cell to start/advance infection.
• The elementary body is taken up into host
cells by phagocytosis.
 Lifecycle and pathogenesis
• Once inside the cell the elementary body
transforms into the reproductive form called a
reticulate body which is metabolically active
and multiplies repeatedly by binary fission.
• When multiplication ceases, the reticulate
bodies are transformed into elementary
bodies and released from the host cell by
cytolysis resulting in host cell death.
 Clinical significance
• Chlamydia trachomatis
– Primarily a human pathogen
– Causes ocular/eye infections (Trachoma,
keratoconjunctivitis)
– Genital infection-Chlamydia(urethritis
,lymphogranuloma venereum in women and
men, cervicitis that may progress to endometritis
and salpingitis(inflammation of the fallopian
tubes) in women)
– Neonatal infection (conjunctivitis and
pneumonia)
 Trachoma

Lymphogranuloma
venereum
 Diagnosis and treatment
Diagnosis
• Direct fluorescent antibody tests
• Culture (tissue culture in human cell lines)
• Serology
• Nucleic acid based tests e.g. PCR

Treatment
• Sensitive to tetracyclines e.g. doxycyline and
macrolides e.g. azithromycin and
erythromycin
• Chlamydia are not susceptible to antibiotics
that do not penetrate cells efficiently.