{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:23:50Z","timestamp":1787559830325,"version":"build-2736575974"},"reference-count":33,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32302881"],"award-info":[{"award-number":["32302881"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32302881"],"award-info":[{"award-number":["32302881"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011785","name":"Guangxi Key Research and Development Program","doi-asserted-by":"publisher","award":["FN2600640468"],"award-info":[{"award-number":["FN2600640468"]}],"id":[{"id":"10.13039\/501100011785","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011785","name":"Guangxi Key Research and Development Program","doi-asserted-by":"publisher","award":["AB23075145"],"award-info":[{"award-number":["AB23075145"]}],"id":[{"id":"10.13039\/501100011785","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007198","name":"Shanghai Agricultural Science and Technology Innovation Project","doi-asserted-by":"publisher","award":["2025-02-08-00-12-F00042"],"award-info":[{"award-number":["2025-02-08-00-12-F00042"]}],"id":[{"id":"10.13039\/501100007198","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Central Public-interest Scientific Institution Basal Research Fund","award":["Y2026YC46"],"award-info":[{"award-number":["Y2026YC46"]}]},{"name":"Central Public-interest Scientific Institution Basal Research Fund","award":["2026JB13"],"award-info":[{"award-number":["2026JB13"]}]},{"DOI":"10.13039\/501100012421","name":"Agricultural Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["CAAS-ASTIP-2026-SHVRI"],"award-info":[{"award-number":["CAAS-ASTIP-2026-SHVRI"]}],"id":[{"id":"10.13039\/501100012421","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Avian pathogenic Escherichia coli (APEC) induces avian colibacillosis and brings huge economic losses to global poultry production. The small alarmone (p)ppGpp mediates the bacterial stringent response, a vital pathway modulating microbial stress adaptation and pathogenic capacity. The functions of the (p)ppGpp synthase gene relA in APEC pathogenesis remain poorly characterized. In this study, we constructed a relA deletion mutant (\u0394relA) and its complemented strain (C\u0394relA). The phenotypic and pathogenic characteristics of these strains were investigated. The results showed that deletion of relA did not significantly affect bacterial growth or motility. However, the \u0394relA strain showed increased susceptibility to aminoglycoside antibiotics. Furthermore, the enhanced interbacterial competition of the mutant was associated with the upregulation of core genes in the type VI secretion system (T6SS). Importantly, relA was essential for APEC adhesion to and invasion of avian DF-1 cells, as well as for colonization and virulence in ducklings, where \u0394relA exhibited significantly attenuated infectivity and reduced bacterial loads in the liver and spleen. Furthermore, transcriptomic analysis revealed that RelA deletion downregulated genes involved in integral components of the membrane, and further assays confirmed compromised membrane integrity in the mutant strain. These findings suggest that RelA maintains membrane integrity, which underpins its contributions to antibiotic resistance and virulence. These findings indicate that relA plays a key role in APEC virulence, antibiotic resistance, and membrane homeostasis, and could provide a theoretical basis for targeting the stringent response as a potential strategy to control avian colibacillosis.<\/jats:p>","DOI":"10.3390\/microorganisms14081803","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:05:41Z","timestamp":1786953941000},"page":"1803","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The (p)ppGpp Synthetase RelA Contributes to Virulence, Competition Capability and Antibiotic Resistance of Avian Pathogenic Escherichia coli"],"prefix":"10.3390","volume":"14","author":[{"given":"Jiangang","family":"Hu","sequence":"first","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 20241 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3235-1855","authenticated-orcid":false,"given":"Doss\u00eah Jean Ap\u00f4tre","family":"Afayibo","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 20241 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 20241 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 20241 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 20241 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqi","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 20241 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 20241 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Deng","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 20241 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3259-1637","authenticated-orcid":false,"given":"Yanqing","family":"Bao","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 20241 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Qi","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 20241 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxing","family":"Tian","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 20241 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohui","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 20241 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104359","DOI":"10.1016\/j.psj.2024.104359","article-title":"Avian pathogenic Escherichia coli (APEC): Current insights and future challenges","volume":"103","author":"Nawaz","year":"2024","journal-title":"Poult. 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