期刊
PLOS BIOLOGY
卷 13, 期 9, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.1002229
关键词
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资金
- MRC Confidence in Concepts award
- Royal Society Research Fellowship
- Oxford NIHR Biomedical Research Centre
- UKCRC Modernising Medical Microbiology Consortium
- UKCRC Translational Infection Research Initiative - Medical Research Council
- National Institute for Health Research of UK Department of Health [G0800778]
- Wellcome Trust [087646/Z/08/Z]
- Wellcome Trust Clinical Research Training Fellow [101611/Z/13/Z]
- Wellcome Trust and the Royal Society [101237/Z/13/Z]
- Wellcome Trust core funding [090532/Z/09/Z]
- Biotechnology and Biological Sciences Research Council
- MRC [MC_PC_13058, G0800778] Funding Source: UKRI
- Medical Research Council [G0800778, MC_PC_13058] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10047] Funding Source: researchfish
- Wellcome Trust [101611/Z/13/Z] Funding Source: Wellcome Trust
Bacterial virulence is a multifaceted trait where the interactions between pathogen and host factors affect the severity and outcome of the infection. Toxin secretion is central to the biology of many bacterial pathogens and is widely accepted as playing a crucial role in disease pathology. To understand the relationship between toxicity and bacterial virulence in greater depth, we studied two sequenced collections of the major human pathogen Staphylococcus aureus and found an unexpected inverse correlation between bacterial toxicity and disease severity. By applying a functional genomics approach, we identified several novel toxicity-affecting loci responsible for the wide range in toxic phenotypes observed within these collections. To understand the apparent higher propensity of low toxicity isolates to cause bacteraemia, we performed several functional assays, and our findings suggest that within-host fitness differences between high- and low-toxicity isolates in human serum is a contributing factor. As invasive infections, such as bacteraemia, limit the opportunities for onward transmission, highly toxic strains could gain an additional between-host fitness advantage, potentially contributing to the maintenance of toxicity at the population level. Our results clearly demonstrate how evolutionary trade-offs between toxicity, relative fitness, and transmissibility are critical for understanding the multifaceted nature of bacterial virulence.
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