Within-Host Evolution of Staphylococcus aureus during Asymptomatic Carriage

被引：155

作者：

Golubchik, Tanya ^{[1
]}

Batty, Elizabeth M. ^{[1
]}

Miller, Ruth R. ^{[2
,3
]}

Farr, Helen ^{[2
,3
]}

Young, Bernadette C. ^{[2
]}

Larner-Svensson, Hanna ^{[3
,4
]}

Fung, Rowena ^{[2
,3
]}

Godwin, Heather ^{[5
]}

Knox, Kyle ^{[6
]}

Votintseva, Antonina ^{[2
,3
]}

Everitt, Richard G. ^{[2
]}

Street, Teresa ^{[1
]}

Cule, Madeleine ^{[1
]}

Ip, Camilla L. C. ^{[1
]}

Didelot, Xavier ^{[1
]}

Peto, Timothy E. A. ^{[2
,3
]}

Harding, Rosalind M. ^{[7
]}

Wilson, Daniel J. ^{[2
,4
]}

Crook, Derrick W. ^{[2
,3
]}

Bowden, Rory ^{[1
,3
,4
]}

机构：

[1] Univ Oxford, Dept Stat, Oxford OX1 3TG, England

[2] Univ Oxford, Nuffield Dept Clin Med, Div Expt Med, Oxford, England

[3] Natl Inst Hlth Res, Oxford Biomed Res Ctr, Oxford, England

[4] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[5] Natl Hlth Serv Trust, Oxford Univ Hosp, Oxford, England

[6] Univ Oxford, Dept Primary Care Hlth Sci, Oxford, England

[7] Univ Oxford, Dept Zool, Oxford OX1 3PS, England

来源：

PLOS ONE | 2013年 / 8卷 / 05期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

PANTON-VALENTINE LEUKOCIDIN; METHICILLIN-RESISTANT; NASAL CARRIAGE; LINKAGE DISEQUILIBRIUM; NUCLEOTIDE-SEQUENCE; RECOMBINATION; DYNAMICS; BACTEREMIA; POPULATION; PROTEIN;

D O I：

10.1371/journal.pone.0061319

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background: Staphylococcus aureus is a major cause of healthcare associated mortality, but like many important bacterial pathogens, it is a common constituent of the normal human body flora. Around a third of healthy adults are carriers. Recent evidence suggests that evolution of S. aureus during nasal carriage may be associated with progression to invasive disease. However, a more detailed understanding of within-host evolution under natural conditions is required to appreciate the evolutionary and mechanistic reasons why commensal bacteria such as S. aureus cause disease. Therefore we examined in detail the evolutionary dynamics of normal, asymptomatic carriage. Sequencing a total of 131 genomes across 13 singly colonized hosts using the Illumina platform, we investigated diversity, selection, population dynamics and transmission during the short-term evolution of S. aureus. Principal Findings: We characterized the processes by which the raw material for evolution is generated: micro-mutation (point mutation and small insertions/deletions), macro-mutation (large insertions/deletions) and the loss or acquisition of mobile elements (plasmids and bacteriophages). Through an analysis of synonymous, non-synonymous and intergenic mutations we discovered a fitness landscape dominated by purifying selection, with rare examples of adaptive change in genes encoding surface-anchored proteins and an enterotoxin. We found evidence for dramatic, hundred-fold fluctuations in the size of the within-host population over time, which we related to the cycle of colonization and clearance. Using a newly-developed population genetics approach to detect recent transmission among hosts, we revealed evidence for recent transmission between some of our subjects, including a husband and wife both carrying populations of methicillin-resistant S. aureus (MRSA). Significance: This investigation begins to paint a picture of the within-host evolution of an important bacterial pathogen during its prevailing natural state, asymptomatic carriage. These results also have wider significance as a benchmark for future systematic studies of evolution during invasive S. aureus disease.

引用

页数：14