University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Department of Microbiology and Physiological Systems
Publication Date
2018-04-28
Document Type
Article Preprint
Disciplines
Immunology and Infectious Disease | Microbiology
Abstract
Virulence of Yersinia pestis in mammals requires the type III secretion system, which delivers seven effector proteins into the cytoplasm of host cells to undermine immune responses. All seven of these effectors are conserved across Y. pestis strains, but three -- YopJ, YopT, and YpkA -- are apparently dispensable for virulence. Some degree of functional redundancy between effector proteins would explain both observations. Here, we use a combinatorial genetic approach to define the minimal subset of effectors required for full virulence in mice following subcutaneous infection. We found that a Y. pestis strain lacking YopJ, YopT, and YpkA is attenuated for virulence in mice, and that addition of any one of these effectors to this strain increases lethality significantly. YopJ, YopT, and YpkA likely contribute to virulence via distinct mechanisms. YopJ is uniquely able to cause macrophage cell death in vitro and to suppress accumulation of inflammatory cells to foci of bacterial growth in deep tissue, whereas YopT and YpkA cannot. The synthetic phenotypes that emerge when YopJ, YopT, and YpkA are removed in combination provide evidence that each enhances Y. pestis virulence, and that YopT and YpkA act through a mechanism distinct from that of YopJ.
Keywords
microbiology, Yersinia pestis, effector proteins, YopJ, YopT, YpkA, mice
Rights and Permissions
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
10.1101/310243
Source
bioRxiv 310243; doi: https://doi.org/10.1101/310243. Link to preprint on bioRxiv service.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Palace SG, Proulx MK, Szabady RL, Goguen JD. (2018). Gain of Function Analysis Reveals Non-Redundant Roles for the Yersinia pestis Type III Secretion System Effectors YopJ, YopT, and YpkA [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/310243. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1531
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.