The
            <i>blp</i>
            Bacteriocins of
            <i>Streptococcus pneumoniae</i>
            Mediate Intraspecies Competition both In Vitro and In Vivo

Dawid, Suzanne; Roche, Aoife M.; Weiser, Jeffrey N.

doi:10.1128/iai.01775-05

Cited by 155 publications

(218 citation statements)

References 27 publications

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“…Indeed, there is evidence for noncapsular factors contributing to duration of carriage: Weinberger et al have reported within-serotype variation in resistance to neutrophil-mediated killing in vitro (a likely predictor of duration of carriage) for isolates with different genetic backgrounds (11). Possible candidates for genetic factors influencing duration of carriage include bacterial adhesins (as suggested by Weinberger et al), metabolic genes and bacteriocins, which likely mediate killing of nonisogenic strains and could therefore play a role in strain knockout (18).…”

Section: Discussionmentioning

confidence: 99%

Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage

Lehtinen

Blanquart

Croucher

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

130

195

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Understanding how changes in antibiotic consumption affect the prevalence of antibiotic resistance in bacterial pathogens is important for public health. In a number of bacterial species, including Streptococcus pneumoniae, the prevalence of resistance has remained relatively stable despite prolonged selection pressure from antibiotics. The evolutionary processes allowing the robust coexistence of antibiotic sensitive and resistant strains are not fully understood. While allelic diversity can be maintained at a locus by direct balancing selection, there is no evidence for such selection acting in the case of resistance. In this work, we propose a mechanism for maintaining coexistence at the resistance locus: linkage to a second locus that is under balancing selection and that modulates the fitness effect of resistance. We show that duration of carriage plays such a role, with long duration of carriage increasing the fitness advantage gained from resistance. We therefore predict that resistance will be more common in strains with a long duration of carriage and that mechanisms maintaining diversity in duration of carriage will also maintain diversity in antibiotic resistance. We test these predictions in S. pneumoniae and find that the duration of carriage of a serotype is indeed positively correlated with the prevalence of resistance in that serotype. These findings suggest heterogeneity in duration of carriage is a partial explanation for the coexistence of sensitive and resistant strains and that factors determining bacterial duration of carriage will also affect the prevalence of resistance.A ntibacterial resistance is a serious threat to public health, with resistant strains emerging in numerous pathogens. Although estimates of resistance levels vary by region, pathogen, and antibiotic type, a common feature is that fixation of resistance is rarely observed: sensitive and resistant strains tend to coexist robustly. For example, according to the European Antimicrobial Resistance Surveillance Network (EARS-Net; available at ecdc.europa.eu) (1), the prevalence of penicillin and macrolide nonsensitivity in Streptococcus pneumoniae has been stable at around 10 and 15% respectively for the past 15 years in Europe. Similarly, EARS-Net estimates of multidrug resistance in Klebsiella pneumoniae have varied around 20% since 2009 and those for methicillin resistance in Staphylococcus aureus have ranged between 15 and 25% from 1999 onwards, with no persisting directional trend.The stable coexistence of sensitive and resistant strains is unexpected: because these strains compete for the same hosts, simple ecological models predict that the fitter strain would dominate and the weaker strain become extinct ("competitive exclusion"). Understanding how coexistence is maintained is therefore important for predicting the prevalence of resistant strains and for explaining the approximately linear relationship between regional antibiotic consumption and resistance (2). Predicting the prevalence of resistance is, in turn, crucial...

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Section: Discussionmentioning

confidence: 99%

Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage

Lehtinen

Blanquart

Croucher

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

130

195

View full text Add to dashboard Cite

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“…Strain 6Aply was generated by transformation with chromosomal DNA from D39ply with selection for erythromycin resistance (1 g/ml) followed by serial backtransformation (6). Loss of pneumolysin expression was confirmed by Western blotting using a monoclonal antibody to pneumolysin (Novocastra, Newcastle upon Tyne, United Kingdom).…”

Section: Methodsmentioning

confidence: 99%

Live Attenuated Streptococcus pneumoniae Strains Induce Serotype-Independent Mucosal and Systemic Protection in Mice

Roche¹,

King²,

Weiser

2007

Infect Immun

Self Cite

118

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Streptococcus pneumoniae is an important human pathogen causing both mucosal (otitis media and pneumonia) and systemic (sepsis and meningitis) diseases. Due to increasing rates of antibiotic resistance, there is an urgent need to improve prevention of pneumococcal disease. Two currently licensed vaccines have been successful in reducing pneumococcal disease, but there are limitations with their use and effectiveness. Another approach for prevention is the use of live attenuated vaccines. Here we investigate the safety and protection induced by live attenuated strains of S. pneumoniae containing combinations of deletions in genes encoding three of its major virulence determinants: capsular polysaccharide (cps), pneumolysin (ply), and pneumococcal surface protein A (pspA). Both the cps and ply/pspA mutants of a virulent type 6A isolate were significantly attenuated in a mouse model of sepsis. These attenuated strains retained the ability to colonize the upper respiratory tract. A single intranasal administration of live attenuated vaccine without adjuvant was sufficient to induce both systemic and mucosal protection from challenge with a high dose of the parent strain. Immunization with cps mutants demonstrated cross-protective immunity following challenge with a distantly related isolate. Serum and mucosal antibody titers were significantly increased in mice immunized with the vaccine strains, and this antibody is required for full protection, as MT mice, which do not make functional, specific antibody, were not protected by immunization with vaccine strains. Thus, colonization by live attenuated S. pneumoniae is a potentially safe and less complex vaccine strategy that may offer broad protection.

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“…Also seen were the expected diversity of lysins (Seo et al 2010), holins (Wang et al 2000), bacteriocins (Dawid et al 2007), restriction/modification systems (Kobayashi 2001), and virulence factors (O'Brien et al 1984;Lainhart et al 2009;Campos et al 2010).…”

Section: Genome Research 1621mentioning

confidence: 99%

The human gut virome: Inter-individual variation and dynamic response to diet

Minot¹,

Sinha²,

Chen³

et al. 2011

Genome Res.

821

902

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Immense populations of viruses are present in the human gut and other body sites. Understanding the role of these populations (the human “virome”) in health and disease requires a much deeper understanding of their composition and dynamics in the face of environmental perturbation. Here, we investigate viromes from human subjects on a controlled feeding regimen. Longitudinal fecal samples were analyzed by metagenomic sequencing of DNA from virus-like particles (VLP) and total microbial communities. Assembly of 336 Mb of VLP sequence yielded 7175 contigs, many identifiable as complete or partial bacteriophage genomes. Contigs were rich in viral functions required in lytic and lysogenic growth, as well as unexpected functions such as viral CRISPR arrays and genes for antibiotic resistance. The largest source of variance among virome samples was interpersonal variation. Parallel deep-sequencing analysis of bacterial populations showed covaration of the virome with the larger microbiome. The dietary intervention was associated with a change in the virome community to a new state, in which individuals on the same diet converged. Thus these data provide an overview of the composition of the human gut virome and associate virome structure with diet.

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The blp Bacteriocins of Streptococcus pneumoniae Mediate Intraspecies Competition both In Vitro and In Vivo

Cited by 155 publications

References 27 publications

Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage

Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage

Live Attenuated Streptococcus pneumoniae Strains Induce Serotype-Independent Mucosal and Systemic Protection in Mice

The human gut virome: Inter-individual variation and dynamic response to diet

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