What is the mechanism for persistent coexistence of drug-susceptible and drug-resistant strains of
            <i>Streptococcus pneumoniae</i>
            ?

Colijn, Caroline; Cohen, Ted; Fraser, Christophe; Hanage, William P.; Goldstein, Édward; Givon-Lavi, Noga; Dagan, Ron; Lipsitch, Marc

doi:10.1098/rsif.2009.0400

Cited by 86 publications

(182 citation statements)

References 38 publications

Supporting

Mentioning

175

Contrasting

Order By: Relevance

“…A more common but less well understood scenario is one where the competing species induce partial immunity against one another. There has been significant work trying to elucidate the conditions under which such partial immunity leads to coexistence [25,11,26] but a complete theory has not yet emerged.…”

Section: Introductionmentioning

confidence: 98%

Interacting viruses in networks

Beutel

Prakash

Rosenfeld

et al. 2012

Proceedings of the 18th ACM SIGKDD International Conference on Knowledge Discovery and Data Mining

View full text Add to dashboard Cite

Suppose we have two competing ideas/products/viruses, that propagate over a social or other network. Suppose that they are strong/virulent enough, so that each, if left alone, could lead to an epidemic. What will happen when both operate on the network? Earlier models assume that there is perfect competition: if a user buys product 'A' (or gets infected with virus 'X'), she will never buy product 'B' (or virus 'Y'). This is not always true: for example, a user could install and use both Firefox and Google Chrome as browsers. Similarly, one type of flu may give partial immunity against some other similar disease.In the case of full competition, it is known that 'winner takes all,' that is the weaker virus/product will become extinct. In the case of no competition, both viruses survive, ignoring each other. What happens in-between these two extremes?We show that there is a phase transition: if the competition is harsher than a critical level, then 'winner takes all;' otherwise, the weaker virus survives. These are the contributions of this paper (a) the problem definition, which is novel even in epidemiology literature [3,17,35] (b) the phase-transition result and (c) experiments on real data, illustrating the suitability of our results.

show abstract

Section: Introductionmentioning

confidence: 98%

Interacting viruses in networks

Beutel

Prakash

Rosenfeld

et al. 2012

Proceedings of the 18th ACM SIGKDD International Conference on Knowledge Discovery and Data Mining

View full text Add to dashboard Cite

show abstract

“…Colijn et al explored whether coexistence of sensitive and resistant strains in the pneumococcus could be reproduced using a number of structurally neutral coexistence-promoting mechanisms (including habitat heterogeneity, within-host competition and lowered competition for hosts) (6). Although coexistence was possible in all models, it was highly sensitive to antibiotic consumption rate and the fitness cost of resistance.…”

Section: Significancementioning

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.

Self Cite

126

187

View full text Add to dashboard Cite

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...

show abstract

“…In the non-neutral cases where coexistence is generic, such an arrow will generally not move the system across the bifurcation boundary. Nicoli [37] illustrated these diagrams for a wide range of neutral and non-neutral models; neutral models generically show the competitive exclusion-type bifurcation diagram (similar to that shown in [11]) in which the only prevalent strain is the one with a higher R 0 .…”

Section: Discussionmentioning

confidence: 99%

“…Neutrality requires that coinfected individuals can have one strain "knocked out" by the other (strain replacement). Otherwise, a rare strain has an advantage by virtue of being rare [11,28]. In our model, infection with a second strain results in coinfection rather than super-infection, because super-infection (one strain entirely and instantly displacing the other) is a strong assumption about inter-strain competition.…”

Section: Modeling Strategymentioning

confidence: 99%