{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:58:47Z","timestamp":1790812727169,"version":"4.1.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Plague caused by <jats:italic>Yersinia pestis<\/jats:italic> remains a public health threat worldwide. Because multidrug-resistant <jats:italic>Y. pestis<\/jats:italic> strains have been found in both humans and animals, phage therapy has attracted increasing attention as an alternative strategy against plague. However, phage resistance is a potential drawback of phage therapies, and the mechanism of phage resistance in <jats:italic>Y. pestis<\/jats:italic> is yet to be investigated. In this study, we obtained a bacteriophage-resistant strain of <jats:italic>Y. pestis<\/jats:italic> (S56) by continuously challenging <jats:italic>Y. pestis<\/jats:italic> 614F with the bacteriophage Yep-phi. Genome analysis identified three mutations in strain S56: <jats:italic>waaA<\/jats:italic>* (9-bp in-frame deletion <jats:sub>249<\/jats:sub>GTCATCGTG<jats:sub>257<\/jats:sub>), <jats:italic>cmk*<\/jats:italic> (10-bp frameshift deletion <jats:sub>15<\/jats:sub>CCGGTGATAA<jats:sub>24<\/jats:sub>), and <jats:italic>ail*<\/jats:italic> (1-bp frameshift deletion A<jats:sub>538<\/jats:sub>). WaaA (3-deoxy-D-manno-octulosonic acid transferase) is a key enzyme in lipopolysaccharide biosynthesis. The <jats:italic>waaA*<\/jats:italic> mutation leads to decreased phage adsorption because of the failure to synthesize the lipopolysaccharide core. The mutation in <jats:italic>cmk<\/jats:italic> (encoding cytidine monophosphate kinase) increased phage resistance, independent of phage adsorption, and caused <jats:italic>in vitro<\/jats:italic> growth defects in <jats:italic>Y. pestis.<\/jats:italic> The mutation in <jats:italic>ail<\/jats:italic> inhibited phage adsorption while restoring the growth of the <jats:italic>waaA<\/jats:italic> null mutant and accelerating the growth of the <jats:italic>cmk<\/jats:italic> null mutant. Our results confirmed that mutations in the WaaA\u2013Cmk\u2013Ail cascade in <jats:italic>Y. pestis<\/jats:italic> contribute to resistance against bacteriophage. Our findings help in understanding the interactions between <jats:italic>Y. pestis<\/jats:italic> and its phages.<\/jats:p>","DOI":"10.3389\/fcimb.2023.1174510","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T04:41:45Z","timestamp":1685076105000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Interplays of mutations in waaA, cmk, and ail contribute to phage resistance in Yersinia pestis"],"prefix":"10.3389","volume":"13","author":[{"given":"Lisheng","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhizhen","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruichen","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cunxiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youquan","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafang","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongmin","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujun","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1099\/jmm.0.46697-0","article-title":"Treatment of plague: promising alternatives to antibiotics","volume":"55","author":"Anisimov","year":"2006","journal-title":"J. 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