期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 34, 页码 20836-20847出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2006110117
关键词
type VII secretion system; Staphylococcus aureus; zebrafish; membrane-depolarizing toxin; bacterial competition
资金
- Wellcome Trust [WT099084MA, 110183/Z/15/Z, 105606/Z/14/Z]
- UK Biotechnology and Biological Sciences Research Council [BB/H007571/1]
- UK Biotechnology and Biological Sciences Research Council (EASTBIO DTP1 Grant) [BB/J01446X/1]
- Microbiology Society through a Research Visit grant
- China Scholarship Council PhD studentship
- Medical Research Council UK [MC_UU_12016/5]
- European Research Council Consolidator Grant [772853 - ENTRAPMENT]
- Wellcome Trust Senior Research Fellowship [206444/Z/17/Z]
- Lister Institute of Preventive Medicine
- Wellcome Trust [105606/Z/14/Z, 110183/Z/15/Z] Funding Source: Wellcome Trust
- BBSRC [BB/H007571/1] Funding Source: UKRI
- MRC [MC_UU_12016/5, MR/M011224/1, G117/519] Funding Source: UKRI
The type VII protein secretion system (T7SS) is conserved across Staphylococcus aureus strains and plays important roles in virulence and interbacterial competition. To date, only one T7SS substrate protein, encoded in a subset of S. aureus genomes, has been functionally characterized. Here, using an unbiased proteomic approach, we identify TspA as a further T7SS substrate. TspA is encoded distantly from the T7SS gene cluster and is found across all S. aureus strains as well as in Listeria and Enterococci. Heterologous expression of TspA from S. aureus strain RN6390 indicates its C-terminal domain is toxic when targeted to the Escherichia coli periplasm and that it depolarizes the cytoplasmic membrane. The membrane-depolarizing activity is alleviated by coproduction of the membrane-bound Tsal immunity protein, which is encoded adjacent to tspA on the S. aureus chromosome. Using a zebrafish hindbrain ventricle infection model, we demonstrate that the T7SS of strain RN6390 promotes bacterial replication in vivo, and deletion of tspA leads to increased bacterial clearance. The toxin domain of TspA is highly polymorphic and S. aureus strains encode multiple tsal homologs at the tspA locus, suggestive of additional roles in intraspecies competition. In agreement, we demonstrate TspA-dependent growth inhibition of RN6390 by strain COL in the zebrafish infection model that is alleviated by the presence of Tsal homologs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据