OVERVIEW: Background: Most in vitro estimates of MICs and the kinetics of antibiotic-mediated kil... more OVERVIEW: Background: Most in vitro estimates of MICs and the kinetics of antibiotic-mediated killing are obtained with relatively low densities of planktonic bacteria growing exponentially under conditions that are optimal for the activity of the drug. The procedures for obtaining these estimates have the considerable virtues of standardization, reliability and repeatability. Unfortunately the conditions under which they are obtained are rarely met in treated patients. Infecting bacteria are likely to be at relatively high densities and growing under conditions that are not optimal for the action of antibiotics such as in physically-structured populations like multi-cell clumps, as colonies or in biofilms adhering to surfaces of tissues or prosthetic devices.
As a consequence of sequential replacements by clones of higher fitness (periodic selection), bac... more As a consequence of sequential replacements by clones of higher fitness (periodic selection), bacterial populations would be continually purged of genetic variability, and the fate of selectively neutral alleles in very large populations of bacteria would be similar to that in demes of sexually reproducing organisms with small genetically effective population sizes. The significance of periodic selection in reducing genetic variability in these clonally reproducing species is dependent on the amount of genetic exchange between clones (recombination). In an effort to determine the relationship between the rates of periodic selection, recombination and the genetically effective sizes of bacterial populations, a model for periodic selection and infectious gene exchange has been developed and its properties analyzed. It shows that, for a given periodic selection regime, genetically effective population size increases exponentially with the rate of recombination.—With the parameters of t...
Variation in chromosomal DNA in Escherichia coli was studied with probes specific for the P-assoc... more Variation in chromosomal DNA in Escherichia coli was studied with probes specific for the P-associated-pilus (pap) region. The presence of DNA homologous to pap was determined by dot blots. Variation in the number of copies of pap and in the organization of internal and flanking sequences was determined by Southern blot hybridization. The 229 strains studied were also classified by O:K:H serotyping and multilocus enzyme electrophoresis. There was considerable heterogeneity in the presence of pap and distribution of pap-homologous DNA in these E. coli strains from natural sources. In general, there was less variation in pap among strains of the same specific O:K:H serotype and enzyme electrophoretic type than among random isolates. There were, however, E. coli strains identified as members of the same clone by O:K:H serotyping and enzyme electrophoresis that were pap positive and pap negative or had different Southern blot patterns for the pap probes (pap type). There were also isola...
ABSTRACTAntimicrobial peptides (AMPs) are central components of the innate immune system providin... more ABSTRACTAntimicrobial peptides (AMPs) are central components of the innate immune system providing protection against pathogens. Yet, serum and tissue concentrations vary between individuals and with disease conditions. We demonstrate that the human AMP LL-37 lowers the susceptibility to vancomycin in the community-associated methicillin-resistant S. aureus (CA-MRSA) strain FPR3757 (USA300). Vancomycin is used to treat serious MRSA infections, but treatment failures occur despite MRSA strains being tested susceptible according to standard susceptibility methods. Exposure to physiologically relevant concentrations of LL-37 increased the minimum inhibitory concentration (MIC) of S. aureus towards vancomycin by 75%, and resulted in shortened lag-phase and increased colony formation at sub-inhibitory concentrations of vancomycin. Computer simulations using a mathematical antibiotic treatment model indicated that a small increase in MIC might decrease the efficacy of vancomycin in cleari...
SummaryIsolates from the intestinalEscherichia coliflora of 28 members of five families (includin... more SummaryIsolates from the intestinalEscherichia coliflora of 28 members of five families (including parents, children, and household pets) in Amherst, Massachusetts, and Rochester, New York, were characterized by the electrophoretic mobilities of 12 enzymes to estimate the extent of sharing of strains among associated and unassociated hosts. Among the 655 isolates examined, 60 different combinations of electromorphs (electrophoretic types or ETs), each representing a distinctive multilocus genotype, were identified, of which 85% were recovered from only a single individual. On average, 11 % of the ETs isolated from the same family were shared by two or more members; 4·9% of ETs were shared among members of unassociated families living in the same city; and only 2% were shared by families in different cities. All three ETs that were recovered from multiple hosts in the present study are widespread clones that have been isolated from many other host individuals in North America and Swe...
This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDeriva... more This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Protection against lethal infections by bacteriophage may seem the most likely role of restrictio... more Protection against lethal infections by bacteriophage may seem the most likely role of restrictioemodification (R-M) systems in bacteria and the reason for their evolution. There are, however, phenomena which question this phage-mediated selection hypothesis for the maintenance of extant R-M systems. Most prominent among these are the mechanisms phage have to avoid or otherwise limit the effects of the restriction endonucleases produced by their host bacteria. To evaluate the importance of these antirestriction mechanisms in Eschevichia coli, we have examined the sensitivity of coliphage from natural and laboratory sources to a series of type I and I1 R-M systems. The results of our study indicate that, in zlizlo, restriction endonucleases have no effect on a substantial fraction of naturally occurring coliphage. The absence of restriction sites appears to be the most common reason why these phage are unaffected by type I1 restriction endonucleases, but other antirestriction mechanisms also operate. On the other hand, the frequency of naturally occurring coliphage sensitive to restriction appears sufficiently great for phage-mediated selection to be a viable hypothesis for the maintenance of R-M in E. coli and its accessory elements.
I examine the results of studies that used mathematical models of the epidemiology and population... more I examine the results of studies that used mathematical models of the epidemiology and population genetics of antibiotic treatment and resistance in open communities and in hospitals to explore the following issues: the relationship between antibiotic consumption and the frequency of antibiotic resistance in bacterial populations in communities and in hospitals; methods of controlling the growth, dissemination, and persistence of antibiotic resistance in these settings; the extent to which resistance can be controlled; and the speed with which the effects of control measures will be realized. In open communities, it will take years or even decades to see substantial reductions in the frequency of antibiotic resistance solely as a result of more prudent (reduced) use of antibiotics. However, if we can restrict the input of resistant bacteria into hospitals, through the application of infection control and other measures, it should be possible to reduce the frequency of resistance and even eliminate resistant bacteria from these institutions in short order.
Background The first step in invasive disease caused by the normally commensal bacteria Streptoco... more Background The first step in invasive disease caused by the normally commensal bacteria Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae is their colonization of the nasal passages. For any population to colonize a new habitat it is necessary for it to be able to compete with the existing organisms and evade predation. In the case of colonization of these species the competition is between strains of the same and different species of bacteria and the predation is mediated by the host's immune response. Here, we use a neonatal rat model to explore these elements of the ecology of nasal colonization by these occasionally invasive bacteria. Results When neonatal rats are colonized by any one of these species the density of bacteria in the nasal passage rapidly reaches a steady-state density that is species-specific but independent of inoculum size. When novel populations of H. influenzae and S. pneumoniae are introduced into the nasal passages of neonatal ...
... Main navigation links: Search; Submit; Help; Your CDS: Your alerts; Your baskets; Your search... more ... Main navigation links: Search; Submit; Help; Your CDS: Your alerts; Your baskets; Your searches. login. Home > The evolution of sex. ... Book. Title, The evolution of sex : an examination of current ideas. Author(s), Michod, Richard E (ed.) ; Levin, Bruce R (ed.). ...
The dynamics of growth of bacterial populations has been extensively studied for planktonic cells... more The dynamics of growth of bacterial populations has been extensively studied for planktonic cells in well-agitated liquid culture, in which all cells have equal access to nutrients. In the real world, bacteria are more likely to live in physically structured habitats as colonies, within which individual cells vary in their access to nutrients. The dynamics of bacterial growth in such conditions is poorly understood, and, unlike that for liquid culture, there is not a standard broadly used mathematical model for bacterial populations growing in colonies in three dimensions (3-d). By extending the classic Monod model of resource-limited population growth to allow for spatial heterogeneity in the bacterial access to nutrients, we develop a 3-d model of colonies, in which bacteria consume diffusing nutrients in their vicinity. By following the changes in density of E. coli in liquid and embedded in glucose-limited soft agar, we evaluate the fit of this model to experimental data. The mo...
A method is presented to evaluate in vitro the efficacy of antibiotics to treat bacteria growing ... more A method is presented to evaluate in vitro the efficacy of antibiotics to treat bacteria growing as discrete colonies on surfaces and the contribution of the colony structure to the antibiotic susceptibility of bacteria. Using this method, we explored the relative efficacy of six bactericidal and three bacteriostatic antibiotics to inhibit the growth and kill Staphylococcus aureus colonies of different sizes, densities and ages. As measured by the reduction in viable cell density relative to untreated controls, of the bactericidal drugs tested ciprofloxacin and gentamicin were most effective. By this criteria, ampicillin was more effective than oxacillin. Daptomycin and vancomycin were virtually ineffective for treating S. aureus growing as colonies. The bacteriostatic antibiotic tested, tetracycline, linezolid and erythromycin were all able to prevent the growth of S. aureus colonies and did so even more effectively than daptomycin, which is highly bactericidal in liquid culture. T...
Articles on CRISPR commonly open with some variant of the phrase ‘these short-palindromic repeats... more Articles on CRISPR commonly open with some variant of the phrase ‘these short-palindromic repeats and their associated endonucleases (Cas) are an adaptive immune system that exists to protect bacteria and archaea from viruses and infections with other mobile genetic elements’. There is an abundance of genomic data consistent with the hypothesis that CRISPR plays this role in natural populations of bacteria and archaea, and experimental demonstrations with a few species of bacteria and their phage and plasmids show that CRISPR-Cas systems can play this rolein vitro. Not at all clear are the ubiquity, magnitude and nature of the contribution of CRISPR-Cas systems to the ecology and evolution of natural populations of microbes, and the strength of selection mediated by different types of phage and plasmids to the evolution and maintenance of CRISPR-Cas systems. In this perspective, with the aid of heuristic mathematical-computer simulation models, we explore thea prioriconditions under...
A simple epidemiological model is used as a framework to explore the potential efficacy of measur... more A simple epidemiological model is used as a framework to explore the potential efficacy of measures to control antibiotic resistance in community-based self-limiting human infections. The analysis of the properties of this model predict that resistance can be maintained at manageable levels if: first, the rates at which specific antibiotics are used declines with the frequency of resistance to these drugs; second, resistance rarely emerges during therapy; and third, external sources rarely contribute to the entry of resistant bacteria into the community. We discuss the feasibility and limitations of these measures to control the rates of antibiotic resistance and the potential of advances in diagnostic procedures to facilitate this endeavor.
The genes coding for cholera toxin are borne on, and can be infectiously transmitted by, a filame... more The genes coding for cholera toxin are borne on, and can be infectiously transmitted by, a filamentous bacteriophage, raising intriguing questions about the mechanisms and evolution of bacterial pathogenesis, and the taxonomy, epidemiology and control of cholera and other bacterial diseases.
SUMMARYFollowing an unusually heavy rainfall in June 2009, a community-wide outbreak ofCampylobac... more SUMMARYFollowing an unusually heavy rainfall in June 2009, a community-wide outbreak ofCampylobactergastroenteritis occurred in a small Danish town. The outbreak investigation consisted of (1) a cohort study using an e-questionnaire of disease determinants, (2) microbiological study of stool samples, (3) serological study of blood samples from cases and asymptomatic members of case households, and (4) environmental analyses of the water distribution system. The questionnaire study identified 163 cases (respondent attack rate 16%). Results showed a significant dose-response relationship between consumption of tap water and risk of gastroenteritis.Campylobacter jejunibelonging to two relatedflaAtypes were isolated from stool samples. Serum antibody levels againstCampylobacterwere significantly higher in cases than in asymptomatic persons. Water samples were positive for coliform bacteria, and the likely mode of contamination was found to be surface water leaking into the drinking-wate...
Applied and environmental microbiology, Aug 2, 2017
Streptococcus pneumoniae is a main cause of child mortality worldwide, but strains also asymptoma... more Streptococcus pneumoniae is a main cause of child mortality worldwide, but strains also asymptomatically colonize the upper airways of most children forming biofilms. Recent studies have demonstrated that ∼50% of colonized children carry at least two different serotypes (i.e., strains) in the nasopharynx; however, studies of how strains coexist are limited. In this work, we investigated the physiological, genetics, and ecological requirements for the relative distribution of densities, and spatial localization, of pneumococcal strains within biofilm consortia. Consortial biofilms were prepared with vaccine-type strains [i.e., serotype (S)6B, S19F, or S23F] and TIGR4 (S4). Experiments first revealed that the relative density of S6B and S23F was similar in biofilm consortia. The density of S19F strains, however, was reduced to ∼10% in biofilm consortia including either S6B, S23F, or TIGR4, in comparison to S19F mono-strain biofilms. Reduction of S19F density within biofilm consortia w...
Recent studies have shown that most of deaths in the 1918 influenza pandemic were caused by secon... more Recent studies have shown that most of deaths in the 1918 influenza pandemic were caused by secondary bacterial infections, primarily pneumococcal pneumonia. Given the availability of antibiotics and pneumococcal vaccination, how will contemporary populations fare when they are next confronted with pandemic influenza due to a virus with the transmissibility and virulence of that of 1918? To address this question we use a mathematical model and computer simulations. Our model considers the epidemiology of both the influenza virus and pneumonia-causing bacteria and allows for co-infection by these two agents as well as antibiotic treatment, prophylaxis and pneumococcal vaccination. For our simulations we use influenza transmission and virulence parameters estimated from 1918 pandemic data. We explore the anticipated rates of secondary pneumococcal pneumonia and death in populations with different prevalence of pneumococcal carriage and contributions of antibiotic prophylaxis, treatment, and vaccination to these rates. Our analysis predicts that in countries with lower prevalence of pneumococcal carriage and access to antibiotics and pneumococcal conjugate vaccines, there would substantially fewer deaths due to pneumonia in contemporary populations confronted with a 1918-like virus than that observed in the 1918. Our results also predict that if the pneumococcal carriage prevalence is less than 40%, the positive effects of antibiotic prophylaxis and treatment would be manifest primarily at of level of individuals. These antibiotic interventions would have little effect on the incidence of pneumonia in the population at large. We conclude with the recommendation that pandemic preparedness plans should consider co-infection with and the prevalence of carriage of pneumococci and other bacteria responsible for pneumonia. While antibiotics and vaccines will certainly reduce the rate of individual mortality, the factor contributing most to the relatively lower anticipated lethality of a pandemic with a 1918-like influenza virus in contemporary population is the lower prevalence of pneumococcal carriage.
OVERVIEW: Background: Most in vitro estimates of MICs and the kinetics of antibiotic-mediated kil... more OVERVIEW: Background: Most in vitro estimates of MICs and the kinetics of antibiotic-mediated killing are obtained with relatively low densities of planktonic bacteria growing exponentially under conditions that are optimal for the activity of the drug. The procedures for obtaining these estimates have the considerable virtues of standardization, reliability and repeatability. Unfortunately the conditions under which they are obtained are rarely met in treated patients. Infecting bacteria are likely to be at relatively high densities and growing under conditions that are not optimal for the action of antibiotics such as in physically-structured populations like multi-cell clumps, as colonies or in biofilms adhering to surfaces of tissues or prosthetic devices.
As a consequence of sequential replacements by clones of higher fitness (periodic selection), bac... more As a consequence of sequential replacements by clones of higher fitness (periodic selection), bacterial populations would be continually purged of genetic variability, and the fate of selectively neutral alleles in very large populations of bacteria would be similar to that in demes of sexually reproducing organisms with small genetically effective population sizes. The significance of periodic selection in reducing genetic variability in these clonally reproducing species is dependent on the amount of genetic exchange between clones (recombination). In an effort to determine the relationship between the rates of periodic selection, recombination and the genetically effective sizes of bacterial populations, a model for periodic selection and infectious gene exchange has been developed and its properties analyzed. It shows that, for a given periodic selection regime, genetically effective population size increases exponentially with the rate of recombination.—With the parameters of t...
Variation in chromosomal DNA in Escherichia coli was studied with probes specific for the P-assoc... more Variation in chromosomal DNA in Escherichia coli was studied with probes specific for the P-associated-pilus (pap) region. The presence of DNA homologous to pap was determined by dot blots. Variation in the number of copies of pap and in the organization of internal and flanking sequences was determined by Southern blot hybridization. The 229 strains studied were also classified by O:K:H serotyping and multilocus enzyme electrophoresis. There was considerable heterogeneity in the presence of pap and distribution of pap-homologous DNA in these E. coli strains from natural sources. In general, there was less variation in pap among strains of the same specific O:K:H serotype and enzyme electrophoretic type than among random isolates. There were, however, E. coli strains identified as members of the same clone by O:K:H serotyping and enzyme electrophoresis that were pap positive and pap negative or had different Southern blot patterns for the pap probes (pap type). There were also isola...
ABSTRACTAntimicrobial peptides (AMPs) are central components of the innate immune system providin... more ABSTRACTAntimicrobial peptides (AMPs) are central components of the innate immune system providing protection against pathogens. Yet, serum and tissue concentrations vary between individuals and with disease conditions. We demonstrate that the human AMP LL-37 lowers the susceptibility to vancomycin in the community-associated methicillin-resistant S. aureus (CA-MRSA) strain FPR3757 (USA300). Vancomycin is used to treat serious MRSA infections, but treatment failures occur despite MRSA strains being tested susceptible according to standard susceptibility methods. Exposure to physiologically relevant concentrations of LL-37 increased the minimum inhibitory concentration (MIC) of S. aureus towards vancomycin by 75%, and resulted in shortened lag-phase and increased colony formation at sub-inhibitory concentrations of vancomycin. Computer simulations using a mathematical antibiotic treatment model indicated that a small increase in MIC might decrease the efficacy of vancomycin in cleari...
SummaryIsolates from the intestinalEscherichia coliflora of 28 members of five families (includin... more SummaryIsolates from the intestinalEscherichia coliflora of 28 members of five families (including parents, children, and household pets) in Amherst, Massachusetts, and Rochester, New York, were characterized by the electrophoretic mobilities of 12 enzymes to estimate the extent of sharing of strains among associated and unassociated hosts. Among the 655 isolates examined, 60 different combinations of electromorphs (electrophoretic types or ETs), each representing a distinctive multilocus genotype, were identified, of which 85% were recovered from only a single individual. On average, 11 % of the ETs isolated from the same family were shared by two or more members; 4·9% of ETs were shared among members of unassociated families living in the same city; and only 2% were shared by families in different cities. All three ETs that were recovered from multiple hosts in the present study are widespread clones that have been isolated from many other host individuals in North America and Swe...
This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDeriva... more This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Protection against lethal infections by bacteriophage may seem the most likely role of restrictio... more Protection against lethal infections by bacteriophage may seem the most likely role of restrictioemodification (R-M) systems in bacteria and the reason for their evolution. There are, however, phenomena which question this phage-mediated selection hypothesis for the maintenance of extant R-M systems. Most prominent among these are the mechanisms phage have to avoid or otherwise limit the effects of the restriction endonucleases produced by their host bacteria. To evaluate the importance of these antirestriction mechanisms in Eschevichia coli, we have examined the sensitivity of coliphage from natural and laboratory sources to a series of type I and I1 R-M systems. The results of our study indicate that, in zlizlo, restriction endonucleases have no effect on a substantial fraction of naturally occurring coliphage. The absence of restriction sites appears to be the most common reason why these phage are unaffected by type I1 restriction endonucleases, but other antirestriction mechanisms also operate. On the other hand, the frequency of naturally occurring coliphage sensitive to restriction appears sufficiently great for phage-mediated selection to be a viable hypothesis for the maintenance of R-M in E. coli and its accessory elements.
I examine the results of studies that used mathematical models of the epidemiology and population... more I examine the results of studies that used mathematical models of the epidemiology and population genetics of antibiotic treatment and resistance in open communities and in hospitals to explore the following issues: the relationship between antibiotic consumption and the frequency of antibiotic resistance in bacterial populations in communities and in hospitals; methods of controlling the growth, dissemination, and persistence of antibiotic resistance in these settings; the extent to which resistance can be controlled; and the speed with which the effects of control measures will be realized. In open communities, it will take years or even decades to see substantial reductions in the frequency of antibiotic resistance solely as a result of more prudent (reduced) use of antibiotics. However, if we can restrict the input of resistant bacteria into hospitals, through the application of infection control and other measures, it should be possible to reduce the frequency of resistance and even eliminate resistant bacteria from these institutions in short order.
Background The first step in invasive disease caused by the normally commensal bacteria Streptoco... more Background The first step in invasive disease caused by the normally commensal bacteria Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae is their colonization of the nasal passages. For any population to colonize a new habitat it is necessary for it to be able to compete with the existing organisms and evade predation. In the case of colonization of these species the competition is between strains of the same and different species of bacteria and the predation is mediated by the host's immune response. Here, we use a neonatal rat model to explore these elements of the ecology of nasal colonization by these occasionally invasive bacteria. Results When neonatal rats are colonized by any one of these species the density of bacteria in the nasal passage rapidly reaches a steady-state density that is species-specific but independent of inoculum size. When novel populations of H. influenzae and S. pneumoniae are introduced into the nasal passages of neonatal ...
... Main navigation links: Search; Submit; Help; Your CDS: Your alerts; Your baskets; Your search... more ... Main navigation links: Search; Submit; Help; Your CDS: Your alerts; Your baskets; Your searches. login. Home > The evolution of sex. ... Book. Title, The evolution of sex : an examination of current ideas. Author(s), Michod, Richard E (ed.) ; Levin, Bruce R (ed.). ...
The dynamics of growth of bacterial populations has been extensively studied for planktonic cells... more The dynamics of growth of bacterial populations has been extensively studied for planktonic cells in well-agitated liquid culture, in which all cells have equal access to nutrients. In the real world, bacteria are more likely to live in physically structured habitats as colonies, within which individual cells vary in their access to nutrients. The dynamics of bacterial growth in such conditions is poorly understood, and, unlike that for liquid culture, there is not a standard broadly used mathematical model for bacterial populations growing in colonies in three dimensions (3-d). By extending the classic Monod model of resource-limited population growth to allow for spatial heterogeneity in the bacterial access to nutrients, we develop a 3-d model of colonies, in which bacteria consume diffusing nutrients in their vicinity. By following the changes in density of E. coli in liquid and embedded in glucose-limited soft agar, we evaluate the fit of this model to experimental data. The mo...
A method is presented to evaluate in vitro the efficacy of antibiotics to treat bacteria growing ... more A method is presented to evaluate in vitro the efficacy of antibiotics to treat bacteria growing as discrete colonies on surfaces and the contribution of the colony structure to the antibiotic susceptibility of bacteria. Using this method, we explored the relative efficacy of six bactericidal and three bacteriostatic antibiotics to inhibit the growth and kill Staphylococcus aureus colonies of different sizes, densities and ages. As measured by the reduction in viable cell density relative to untreated controls, of the bactericidal drugs tested ciprofloxacin and gentamicin were most effective. By this criteria, ampicillin was more effective than oxacillin. Daptomycin and vancomycin were virtually ineffective for treating S. aureus growing as colonies. The bacteriostatic antibiotic tested, tetracycline, linezolid and erythromycin were all able to prevent the growth of S. aureus colonies and did so even more effectively than daptomycin, which is highly bactericidal in liquid culture. T...
Articles on CRISPR commonly open with some variant of the phrase ‘these short-palindromic repeats... more Articles on CRISPR commonly open with some variant of the phrase ‘these short-palindromic repeats and their associated endonucleases (Cas) are an adaptive immune system that exists to protect bacteria and archaea from viruses and infections with other mobile genetic elements’. There is an abundance of genomic data consistent with the hypothesis that CRISPR plays this role in natural populations of bacteria and archaea, and experimental demonstrations with a few species of bacteria and their phage and plasmids show that CRISPR-Cas systems can play this rolein vitro. Not at all clear are the ubiquity, magnitude and nature of the contribution of CRISPR-Cas systems to the ecology and evolution of natural populations of microbes, and the strength of selection mediated by different types of phage and plasmids to the evolution and maintenance of CRISPR-Cas systems. In this perspective, with the aid of heuristic mathematical-computer simulation models, we explore thea prioriconditions under...
A simple epidemiological model is used as a framework to explore the potential efficacy of measur... more A simple epidemiological model is used as a framework to explore the potential efficacy of measures to control antibiotic resistance in community-based self-limiting human infections. The analysis of the properties of this model predict that resistance can be maintained at manageable levels if: first, the rates at which specific antibiotics are used declines with the frequency of resistance to these drugs; second, resistance rarely emerges during therapy; and third, external sources rarely contribute to the entry of resistant bacteria into the community. We discuss the feasibility and limitations of these measures to control the rates of antibiotic resistance and the potential of advances in diagnostic procedures to facilitate this endeavor.
The genes coding for cholera toxin are borne on, and can be infectiously transmitted by, a filame... more The genes coding for cholera toxin are borne on, and can be infectiously transmitted by, a filamentous bacteriophage, raising intriguing questions about the mechanisms and evolution of bacterial pathogenesis, and the taxonomy, epidemiology and control of cholera and other bacterial diseases.
SUMMARYFollowing an unusually heavy rainfall in June 2009, a community-wide outbreak ofCampylobac... more SUMMARYFollowing an unusually heavy rainfall in June 2009, a community-wide outbreak ofCampylobactergastroenteritis occurred in a small Danish town. The outbreak investigation consisted of (1) a cohort study using an e-questionnaire of disease determinants, (2) microbiological study of stool samples, (3) serological study of blood samples from cases and asymptomatic members of case households, and (4) environmental analyses of the water distribution system. The questionnaire study identified 163 cases (respondent attack rate 16%). Results showed a significant dose-response relationship between consumption of tap water and risk of gastroenteritis.Campylobacter jejunibelonging to two relatedflaAtypes were isolated from stool samples. Serum antibody levels againstCampylobacterwere significantly higher in cases than in asymptomatic persons. Water samples were positive for coliform bacteria, and the likely mode of contamination was found to be surface water leaking into the drinking-wate...
Applied and environmental microbiology, Aug 2, 2017
Streptococcus pneumoniae is a main cause of child mortality worldwide, but strains also asymptoma... more Streptococcus pneumoniae is a main cause of child mortality worldwide, but strains also asymptomatically colonize the upper airways of most children forming biofilms. Recent studies have demonstrated that ∼50% of colonized children carry at least two different serotypes (i.e., strains) in the nasopharynx; however, studies of how strains coexist are limited. In this work, we investigated the physiological, genetics, and ecological requirements for the relative distribution of densities, and spatial localization, of pneumococcal strains within biofilm consortia. Consortial biofilms were prepared with vaccine-type strains [i.e., serotype (S)6B, S19F, or S23F] and TIGR4 (S4). Experiments first revealed that the relative density of S6B and S23F was similar in biofilm consortia. The density of S19F strains, however, was reduced to ∼10% in biofilm consortia including either S6B, S23F, or TIGR4, in comparison to S19F mono-strain biofilms. Reduction of S19F density within biofilm consortia w...
Recent studies have shown that most of deaths in the 1918 influenza pandemic were caused by secon... more Recent studies have shown that most of deaths in the 1918 influenza pandemic were caused by secondary bacterial infections, primarily pneumococcal pneumonia. Given the availability of antibiotics and pneumococcal vaccination, how will contemporary populations fare when they are next confronted with pandemic influenza due to a virus with the transmissibility and virulence of that of 1918? To address this question we use a mathematical model and computer simulations. Our model considers the epidemiology of both the influenza virus and pneumonia-causing bacteria and allows for co-infection by these two agents as well as antibiotic treatment, prophylaxis and pneumococcal vaccination. For our simulations we use influenza transmission and virulence parameters estimated from 1918 pandemic data. We explore the anticipated rates of secondary pneumococcal pneumonia and death in populations with different prevalence of pneumococcal carriage and contributions of antibiotic prophylaxis, treatment, and vaccination to these rates. Our analysis predicts that in countries with lower prevalence of pneumococcal carriage and access to antibiotics and pneumococcal conjugate vaccines, there would substantially fewer deaths due to pneumonia in contemporary populations confronted with a 1918-like virus than that observed in the 1918. Our results also predict that if the pneumococcal carriage prevalence is less than 40%, the positive effects of antibiotic prophylaxis and treatment would be manifest primarily at of level of individuals. These antibiotic interventions would have little effect on the incidence of pneumonia in the population at large. We conclude with the recommendation that pandemic preparedness plans should consider co-infection with and the prevalence of carriage of pneumococci and other bacteria responsible for pneumonia. While antibiotics and vaccines will certainly reduce the rate of individual mortality, the factor contributing most to the relatively lower anticipated lethality of a pandemic with a 1918-like influenza virus in contemporary population is the lower prevalence of pneumococcal carriage.
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