Interplays of mutations in waaA, cmk, and ail contribute to phage resistance in Yersinia pestis

• DOI: 10.3389/fcimb.2023.1174510
• Publication Date: 2023-05-26T04:41:45Z
• Authors: Lisheng Xiao; Zhizhen Qi; Kai Song; Ruichen Lv; Rong Chen; Haihong Zhao; Hailian Wu; Cunxiang Li; Youquan Xin; Yong Jin; Xiang Li; Xiaoqing Xu; Yafang Tan; Zongmin Du; Yujun Cui; Xuefei Zhang; Ruifu Yang; Xilin Zhao; Yajun Song
• Keywords: Yersinia pestis; plague

Plague caused by Yersinia pestis remains a public health threat worldwide. Because multidrug-resistant Y. strains have been found in both humans and animals, phage therapy has attracted increasing attention as an alternative strategy against plague. However, resistance is potential drawback of therapies, the mechanism yet to be investigated. In this study, we obtained bacteriophage-resistant strain (S56) continuously challenging 614F with bacteriophage Yep-phi. Genome analysis identified three mutations S56: waaA * (9-bp in-frame deletion 249 GTCATCGTG 257 ), cmk* (10-bp frameshift 15 CCGGTGATAA 24 ail* (1-bp A 538 ). WaaA (3-deoxy-D-manno-octulosonic acid transferase) key enzyme lipopolysaccharide biosynthesis. The waaA* mutation leads decreased adsorption because failure synthesize core. cmk (encoding cytidine monophosphate kinase) increased resistance, independent adsorption, vitro growth defects pestis. ail inhibited while restoring null mutant accelerating mutant. Our results confirmed that WaaA–Cmk–Ail cascade contribute bacteriophage. findings help understanding interactions between its phages.