Competition among Streptococcus pneumoniae for intranasal colonization in a mouse model

Lipsitch, Marc; Dykes, Janet K.; Johnson, Scott E.; Ades, Edwin W.; King, Janice; Briles, David E.; Carlone, George M.

doi:10.1016/s0264-410x(00)00046-3

Cited by 111 publications

(93 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since the observed genetic homology was confirmed by MLST analysis, our data suggest that a large number of recombinational events at the capsular loci have occurred within these clusters. This is in line with previous data from the United States and Latin America, where the major (resistant) clones also show multiple serotypes as a result of capsular serotype switch (9,10,16,22,29). Wolf et al (33) have shown that these events occur even more often in susceptible pneumococcal clones, which is in line with our findings.…”

Section: Discussionsupporting

confidence: 94%

Molecular Epidemiology of Pneumococcal Colonization in Response to Pneumococcal Conjugate Vaccination in Children with Recurrent Acute Otitis Media

et al. 2005

View full text Add to dashboard Cite

A randomized double-blind trial with a 7-valent pneumococcal conjugate vaccine was conducted in The Netherlands among 383 children, aged 1 to 7 years, with a history of recurrent acute otitis media. No effect of vaccination on the pneumococcal colonization rate was found. However, a shift in serotype distribution was clearly observed (R. Veenhoven et al., Lancet 361:2189-2195, 2003). We investigated the molecular epidemiology of 921 pneumococcal isolates retrieved from both the pneumococcal vaccine (PV) and control vaccine (CV) groups during the vaccination study. Within individuals a high turnover rate of pneumococcal restriction fragment end labeling genotypes, which was unaffected by vaccination, was observed. Comparison of the genetic structures before and after completion of the vaccination scheme revealed that, despite a shift in serotypes, there was clustering of 70% of the pneumococcal populations. The remaining isolates (30%) were equally observed in the PV and CV groups. In addition, the degree of genetic clustering was unaffected by vaccination. However, within the population genetic structure, nonvaccine serotype clusters with the serotypes 11, 15, and 23B became predominant over vaccine-type clusters after vaccination. Finally, overall pneumococcal resistance was low (14%), and, albeit not significant, a reduction in pneumococcal resistance as a result of pneumococcal vaccination was observed. Molecular surveillance of colonization in Dutch children shows no effect of pneumococcal conjugate vaccination on the degree of genetic clustering and the genetic structure of the pneumococcal population. However, within the genetic pneumococcal population structure, a clear shift toward nonvaccine serotype clusters was observed.

show abstract

Section: Discussionsupporting

confidence: 94%

Molecular Epidemiology of Pneumococcal Colonization in Response to Pneumococcal Conjugate Vaccination in Children with Recurrent Acute Otitis Media

et al. 2005

View full text Add to dashboard Cite

show abstract

“…In vivo tests of these hypotheses are currently limited by the lack of a good animal model for N. meningitidis. With such an animal model, hypothesis (i) can be tested following the methods employed by Marc Lipsitch and colleagues in their studies of Pneumococcus colonization in laboratory mice (Lipsitch et al 2000). If hypothesis (i) is valid, then strains with phase-shifting genes associated with capsular or other surface antigen-encoding genes, or even global mutators will be more likely to colonize previously immunized mice (or mice with genetically determined immunological differences) than those with lower rates of phase shifting (or without fast shifting genes).…”

Section: Discussionmentioning

confidence: 99%

Epidemiology, hypermutation, within–host evolution and the virulence ofNeisseria meningitidis

Meyers

Levin

Richardson

et al. 2003

Proc. R. Soc. Lond. B

View full text Add to dashboard Cite

Many so-called pathogenic bacteria such as Neisseria meningitidis, Haemophilus influenzae, Staphylococcus aureus and Streptococcus pneumoniae are far more likely to colonize and maintain populations in healthy individuals asymptomatically than to cause disease. Disease is a dead-end for these bacteria: virulence shortens the window of time during which transmission to new hosts can occur and the subpopulations of bacteria actually responsible for disease, like those in the blood or cerebral spinal fluid, are rarely transmitted to new hosts. Hence, the virulence factors underlying their occasional pathogenicity must evolve in response to selection for something other than making their hosts sick. What are those selective pressures? We address this general question of the evolution of virulence in the context of phase shifting in N. meningitidis, a mutational process that turns specific genes on and off, and, in particular, contingency loci that code for virulence determinants such as pili, lipopolysaccharides, capsular polysaccharides and outer membrane proteins. We use mathematical models of the epidemiology and the within-host infection dynamics of N. meningitidis to make the case that rapid phase shifting evolves as an adaptation for colonization of diverse hosts and that the virulence of this bacterium is an inadvertent consequence of shortsighted within-host evolution, which is exasperated by the increased mutation rates associated with phase shifting. We present evidence for and suggest experimental and retrospective tests of these hypotheses.

show abstract

“…In addition, serotype replacement has been observed in experiments in a mouse model [14], and in humans following vaccination programmes [16]. Such findings suggest that resident strains can prevent colonization of the nasopharynx by invading strains, and that vaccination may open an otherwise occupied ecological niche for non-vaccine serotypes [14].…”

Section: Introductionmentioning

confidence: 95%

“…Several lines of evidence suggest that S. pneumoniae strains may compete to establish carriage within hosts. Multiple serotypes co-circulate within host populations [1]; epidemiological modelling suggests that serotypes vary in their ability to displace, and to prevent displacement by, competing serotypes [3,7,10,13,14]. Instances of co-colonization by multiple S. pneumoniae strains have been observed during carriage in humans [15].…”

Section: Introductionmentioning

confidence: 99%

Variation in Streptococcus pneumoniae susceptibility to human antimicrobial peptides may mediate intraspecific competition

2012

View full text Add to dashboard Cite

Streptococcus pneumoniae is a facultative pathogen inhabiting the nasopharynx of humans where it is exposed to a range of antimicrobial peptides (AMPs) of the innate immune response. It is possible therefore that the susceptibility of strains to AMPs plays a role in determining their ability to colonize, and furthermore, that AMPs could mediate competitive interactions between co-colonizing genotypes. However, little is known about patterns of natural variation in AMP susceptibility of S. pneumoniae, and it is unclear whether the susceptibilities of an isolate to multiple human AMPs are correlated. We tested this by characterizing the susceptibility of 31 S. pneumoniae natural isolates to human neutrophil peptide (HNP-1) (a-defensin) and LL-37 (cathelicidin). We observed significant variation in susceptibility between isolates to both AMPs, and in the majority of isolates, susceptibilities to HNP-1 and LL-37 were uncorrelated. Clinical isolates were more susceptible to AMPs than were carriage isolates. The polysaccharide capsule of S. pneumoniae is thought to protect cells against AMPs. However, serotype alone could not explain the observed variation in susceptibility suggesting that genetic background plays an equally important role. We tested directly whether AMPs could mediate competition between isolates using competition experiments in the presence and absence of AMPs. These experiments demonstrated that AMPs could indeed reverse the outcome of competition between selected isolates. AMP-mediated competition could therefore contribute to the maintenance of intraspecific genetic diversity in S. pneumoniae.

show abstract

Competition among Streptococcus pneumoniae for intranasal colonization in a mouse model

Cited by 111 publications

References 9 publications

Molecular Epidemiology of Pneumococcal Colonization in Response to Pneumococcal Conjugate Vaccination in Children with Recurrent Acute Otitis Media

Molecular Epidemiology of Pneumococcal Colonization in Response to Pneumococcal Conjugate Vaccination in Children with Recurrent Acute Otitis Media

Epidemiology, hypermutation, within–host evolution and the virulence ofNeisseria meningitidis

Variation in Streptococcus pneumoniae susceptibility to human antimicrobial peptides may mediate intraspecific competition

Contact Info

Product

Resources

About