Proteogenomic discovery of sORF-encoded peptides associated with bacterial virulence in Yersinia pestis

ABSTRACT: Plague caused by Yersinia pestis is one of the deadliest diseases. However, many molecular mechanisms of bacterial virulence remain unclear. This study engaged in the discovery of small open reading frame (sORF)-encoded peptides (SEPs) in Y. pestis. An integrated proteogenomic pipeline was established, and an atlas containing 76 SEPs was described. Bioinformatic analysis indicated that 20% of these SEPs were secreted or localized to the transmembrane and that 33% contained functional domains. Two SEPs, named SEPs-yp1 and -yp2 and encoded in noncoding regions, were selected by comparative peptidomics analysis under host-specific environments and high-salinity stress. They displayed important roles in the regulation of antiphagocytic capability in a thorough functional assay. Remarkable attenuation of virulence in mice was observed in the SEP-deleted mutants. Further global proteomic analysis indicated that SEPs-yp1 and -yp2 affected the bacterial metabolic pathways, and SEP-yp1 was associated with the bacterial virulence by modulating the expression of key virulence factors of the Yersinia type III secretion system. Our study provides a rich resource for research on Y. pestis and plague, and the findings on SEP-yp1 and SEP-yp2 shed light on the molecular mechanism of bacterial virulence. Shiyang Cao, Xinyue Liu, Yin Huang, and Yanfeng Yan et al. utilized an integrated proteogenomic approach to describe an atlas of small open reading frame-encoded peptides (SEPs) in the pathogen, Yersinia pestis. They demonstrate that two of these SEPs are associated with regulation of bacterial virulence, and altogether develop a valuable resource for future research into Y. pestis physiology.

SUBMITTER: Cao S 

PROVIDER: S-EPMC8563848 | biostudies-literature |

REPOSITORIES: biostudies-literature