Evidence for a two-stage model of microbial infection

Meynell, G. G.; Maw, J.

doi:10.1017/s0022172400041139

Cited by 7 publications

(12 citation statements)

References 24 publications

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“…Later during infection, selected subpopulations of the initial clone may become part of the bacterial population causing disease. These observations are in accordance with a two stage model of infection where independent action generating the initial stochastic event is followed by a dynamic birth-death phase which increases heterogeneity due to strong selection [16], [17], [24]. In the case of the model organism S. pneumoniae , our data show different selective pressures shaping the invasive bacterial population during different phases of infection [16].…”

Section: Discussionsupporting

confidence: 89%

“…The selection for altered function of the ATPase, was found only in a proportion of the bacteria making up the population obtained from blood, compelling evidence that the ATPase mutations must have occurred after the single cell bottleneck. As stated above, the observation of subclones being selected during the bacteremic phase underlines a highly dynamic situation, which extends over the neutral two stage infection models [16], [17], [37].…”

Section: Discussionmentioning

confidence: 99%

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The Role of Host and Microbial Factors in the Pathogenesis of Pneumococcal Bacteraemia Arising from a Single Bacterial Cell Bottleneck

et al. 2014

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The pathogenesis of bacteraemia after challenge with one million pneumococci of three isogenic variants was investigated. Sequential analyses of blood samples indicated that most episodes of bacteraemia were monoclonal events providing compelling evidence for a single bacterial cell bottleneck at the origin of invasive disease. With respect to host determinants, results identified novel properties of splenic macrophages and a role for neutrophils in early clearance of pneumococci. Concerning microbial factors, whole genome sequencing provided genetic evidence for the clonal origin of the bacteraemia and identified SNPs in distinct sub-units of F0/F1 ATPase in the majority of the ex vivo isolates. When compared to parental organisms of the inoculum, ex-vivo pneumococci with mutant alleles of the F0/F1 ATPase had acquired the capacity to grow at low pH at the cost of the capacity to grow at high pH. Although founded by a single cell, the genotypes of pneumococci in septicaemic mice indicate strong selective pressure for fitness, emphasising the within-host complexity of the pathogenesis of invasive disease.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

The Role of Host and Microbial Factors in the Pathogenesis of Pneumococcal Bacteraemia Arising from a Single Bacterial Cell Bottleneck

et al. 2014

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“…Pathogenic bacteria are subject to severe bottlenecks during both spread within and transmission between hosts (15, 21, 22). One outcome of these bottlenecks is a reduction in the amount of genetic variation in the surviving population, which can then limit adaptive potential and propagation as the population is exposed to subsequent selective pressures.…”

Section: Discussionmentioning

confidence: 99%

Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations

Aidley

Rajopadhye

Akinyemi

et al. 2017

mBio

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Phase variation occurs in many pathogenic and commensal bacteria and is a major generator of genetic variability. A putative advantage of phase variation is to counter reductions in variability imposed by nonselective bottlenecks during transmission. Genomes of Campylobacter jejuni, a widespread food-borne pathogen, contain multiple phase-variable loci whose rapid, stochastic variation is generated by hypermutable simple sequence repeat tracts. These loci can occupy a vast number of combinatorial expression states (phasotypes) enabling populations to rapidly access phenotypic diversity. The imposition of nonselective bottlenecks can perturb the relative frequencies of phasotypes, changing both within-population diversity and divergence from the initial population. Using both in vitro testing of C. jejuni populations and a simple stochastic simulation of phasotype change, we observed that single-cell bottlenecks produce output populations of low diversity but with bimodal patterns of either high or low divergence. Conversely, large bottlenecks allow divergence only by accumulation of diversity, while interpolation between these extremes is observed in intermediary bottlenecks. These patterns are sensitive to the genetic diversity of initial populations but stable over a range of mutation rates and number of loci. The qualitative similarities of experimental and in silico modeling indicate that the observed patterns are robust and applicable to other systems where localized hypermutation is a defining feature. We conclude that while phase variation will maintain bacterial population diversity in the face of intermediate bottlenecks, narrow transmission-associated bottlenecks could produce host-to-host variation in bacterial phenotypes and hence stochastic variation in colonization and disease outcomes.

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“…Furthermore, two‐stage infection processes have been proposed for both prion diseases (Kulkarni et al. 2003) and for salmonellas (Meynell and Maw 1968). Nowak et al.…”

Section: Increasing Ip With Low Doses Of Untreated Tse Agent May Reflmentioning

confidence: 99%

The infectivity of transmissible spongiform encephalopathy agent at low doses: the importance of phospholipid

Gale

2006

J Appl Microbiol

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The issue of whether the mechanism of infection is independent or co‐operative for low doses of transmissible spongiform encephalopathy (TSE) agent is critical for risk assessment. The susceptibility (and hence ID50) of individuals with the same prion protein (PrP) genotype may vary considerably with a small proportion being very susceptible. Assuming independent action, the incubation period (IP) would continue to increase until the dose is below the ID50 of the most susceptible individuals in the experiment, at which point it would become constant. This may explain the observed increase in IP with decreasing dose below the apparent ID50 in experiments with untreated TSE agent. In contrast, IPs for autoclaved or NaOH‐treated TSE agent increase greatly at doses

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Evidence for a two-stage model of microbial infection

Cited by 7 publications

References 24 publications

The Role of Host and Microbial Factors in the Pathogenesis of Pneumococcal Bacteraemia Arising from a Single Bacterial Cell Bottleneck

The Role of Host and Microbial Factors in the Pathogenesis of Pneumococcal Bacteraemia Arising from a Single Bacterial Cell Bottleneck

Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations

The infectivity of transmissible spongiform encephalopathy agent at low doses: the importance of phospholipid

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