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Here, we performed competition and survival experiments to confirm that deletion of\n                    <jats:italic>ravA-viaA<\/jats:italic>\n                    increases tolerance of the Gram-negative pathogen\n                    <jats:italic>Vibrio cholerae<\/jats:italic>\n                    to low and high AG concentrations during aerobic growth. Using high-throughput strategies in this species, we identify Cpx and Zra2 two-component systems as new partners of RavA-ViaA. We show that the AG tolerance of\n                    <jats:italic>\u2206ravvia<\/jats:italic>\n                    requires the presence of these membrane stress sensing two-component systems. We propose that deletion of the RavA-ViaA function facilitates the response AGs because of a pre-activated state of Cpx and Zra2 membrane stress response systems. We also find an impact of these genes on vancomycin resistance, and we show that simultaneous inactivation of\n                    <jats:italic>ravvia<\/jats:italic>\n                    function together with envelope stress response systems leads to outer membrane permeabilization. Vancomycin is mostly used for Gram-positive because of its low efficiency for crossing the Gram-negative outer membrane. Targeting of the\n                    <jats:italic>ravA-viaA<\/jats:italic>\n                    operon for inactivation could be a future strategy to allow uptake of vancomycin into multidrug-resistant Gram-negative bacteria.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The RavA-ViaA complex was previously found to sensitize\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      to aminoglycosides (AGs) in anaerobic conditions, but the mechanism is unknown. AGs are antibiotics known for their high efficiency against Gram-negative bacteria. In order to elucidate how the expression of the\n                      <jats:italic>ravA-viaA<\/jats:italic>\n                      genes increases bacterial susceptibility to aminoglycosides, we aimed at identifying partner functions necessary for increased tolerance in the absence of RavA-ViaA, in\n                      <jats:italic>Vibrio cholerae<\/jats:italic>\n                      . We show that membrane stress response systems Cpx and Zra2 are required in the absence of RavA-ViaA, for the tolerance to AGs and for outer membrane integrity. In the absence of these systems, the\n                      <jats:italic>\u2206ravvia<\/jats:italic>\n                      strain\u2019s membrane becomes permeable to external agents such as the antibiotic vancomycin.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01730-23","type":"journal-article","created":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T09:00:58Z","timestamp":1697792458000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["RavA\u2010ViaA antibiotic response is linked to Cpx and Zra2 envelope stress systems in\n                    <i>Vibrio cholerae<\/i>"],"prefix":"10.1128","volume":"11","author":[{"given":"Evelyne","family":"Krin","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UMR3525, Unit\u00e9 Plasticit\u00e9 du G\u00e9nome Bact\u00e9rien , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UMR3525, Unit\u00e9 Plasticit\u00e9 du G\u00e9nome Bact\u00e9rien , Paris, France"},{"name":"Sorbonne Universit\u00e9, Coll\u00e8ge doctoral , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Lang","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UMR3525, Unit\u00e9 Plasticit\u00e9 du G\u00e9nome Bact\u00e9rien , Paris, France"},{"name":"Sorbonne Universit\u00e9, Coll\u00e8ge doctoral , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anamaria","family":"Babosan","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UMR3525, Unit\u00e9 Plasticit\u00e9 du G\u00e9nome Bact\u00e9rien , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6482-6002","authenticated-orcid":false,"given":"Didier","family":"Mazel","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UMR3525, Unit\u00e9 Plasticit\u00e9 du G\u00e9nome Bact\u00e9rien , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3477-2685","authenticated-orcid":true,"given":"Zeynep","family":"Baharoglu","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UMR3525, Unit\u00e9 Plasticit\u00e9 du G\u00e9nome Bact\u00e9rien , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0025-7125(16)30038-4"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.51.3.341-350.1987"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.52.1.153-153.1988"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.173.9.2800-2808.1991"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13687"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.51.4.439-457.1987"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.12.2.163"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2280505"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.133.1.149-157.1978"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.16.6164"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085529"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep24601"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511172200"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-0772-0"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32992-9"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1259"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005629"},{"issue":"0","key":"e_1_3_4_19_2","first-page":"e03302","article-title":"Bioenergetic state of Escherichia coli controls aminoglycoside susceptibility","volume":"0","author":"Khoury JYE","unstructured":"Khoury JYE , Beas JZ , Huguenot A , Py B , Barras F. 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