{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:57:31Z","timestamp":1790776651409,"version":"4.1.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000},"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. Microbiol."],"abstract":"<jats:p>\n                    Although it has been reported that deletion of the response regulator, CpxR, in the CpxRA system confers sensitivity to aminoglycosides (AGAs) and \u03b2-lactams in\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    serovar Typhimurium, the regulatory effects of CpxA on multidrug resistance (MDR) are yet to be fully investigated in this organism. Here, to explore the role of CpxA in MDR, various\n                    <jats:italic>cpxA<\/jats:italic>\n                    mutants including a null mutant (JS\u0394\n                    <jats:italic>cpxA<\/jats:italic>\n                    ), a site-directed mutant (JS\u0394\n                    <jats:italic>cpxA<\/jats:italic>\n                    <jats:sub>38<\/jats:sub>\n                    ) and an internal in-frame deletion mutant (JS\u0394\n                    <jats:italic>\n                      cpxA\n                      <jats:sub>92<\/jats:sub>\n                      <jats:sub>\u2013<\/jats:sub>\n                      <jats:sub>104<\/jats:sub>\n                    <\/jats:italic>\n                    ) of the\n                    <jats:italic>S. enterica<\/jats:italic>\n                    serovar Typhimurium strain JS, were constructed. It was revealed that\n                    <jats:italic>cpxA<\/jats:italic>\n                    and\n                    <jats:italic>cpxR<\/jats:italic>\n                    deletion mutants have opposing roles in the regulation of resistance to AGAs and \u03b2-lactams. Amikacin and cefuroxime can activate the CpxRA system, which results in increased resistance of the wild-type compared with the\n                    <jats:italic>cpxR<\/jats:italic>\n                    deletion mutant. All the\n                    <jats:italic>cpxA<\/jats:italic>\n                    mutations significantly increased resistance to AGAs and \u03b2-lactams due to CpxRA system activation\n                    <jats:italic>via<\/jats:italic>\n                    the phosphorylation of CpxR. Moreover, AckA-Pta-dependent activation of CpxR increased the antibiotic resistance of\n                    <jats:italic>cpxA<\/jats:italic>\n                    deletion mutants. Further research revealed that the AcrAB-TolC conferred resistance to some AGAs and \u03b2-lactams but does not influence the regulation of resistance by CpxRA against these antibiotics. The detection of candidate MDR-related CpxR regulons revealed that the mRNA expression levels of\n                    <jats:italic>spy<\/jats:italic>\n                    ,\n                    <jats:italic>ycca<\/jats:italic>\n                    ,\n                    <jats:italic>ppia<\/jats:italic>\n                    ,\n                    <jats:italic>htpX<\/jats:italic>\n                    ,\n                    <jats:italic>stm3031<\/jats:italic>\n                    , and\n                    <jats:italic>acrD<\/jats:italic>\n                    were upregulated and that of\n                    <jats:italic>ompW<\/jats:italic>\n                    was downregulated in various\n                    <jats:italic>cpxA<\/jats:italic>\n                    mutants. Furthermore, the expression levels of\n                    <jats:italic>nuoA<\/jats:italic>\n                    and\n                    <jats:italic>sdhC<\/jats:italic>\n                    mRNAs were downregulated only in JS\u0394\n                    <jats:italic>\n                      cpxA\n                      <jats:sub>92<\/jats:sub>\n                      <jats:sub>\u2013<\/jats:sub>\n                      <jats:sub>104<\/jats:sub>\n                    <\/jats:italic>\n                    . These results suggested that\n                    <jats:italic>cpxA<\/jats:italic>\n                    mutations contribute to AGAs and \u03b2-lactams resistance, which is dependent on CpxR.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2021.604079","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T23:32:18Z","timestamp":1612395138000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Role of cpxA Mutations in the Resistance to Aminoglycosides and \u03b2-Lactams in Salmonella enterica serovar Typhimurium"],"prefix":"10.3389","volume":"12","author":[{"given":"Wenxian","family":"Jing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuerui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongsheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3729","DOI":"10.1128\/AAC.48.10.3729-3735.2004","article-title":"AcrAB-TolC directs efflux-mediated multidrug resistance in Salmonella enterica serovar typhimurium DT104.","volume":"48","author":"Baucheron","year":"2004","journal-title":"Antimicrob. 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