{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:49:20Z","timestamp":1791308960896,"version":"4.3.1"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2010,8,1]],"date-time":"2010-08-01T00:00:00Z","timestamp":1280620800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    As multidrug resistance increases alarmingly, polymyxin B and colistin are increasingly being used in the clinic to treat serious\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    infections. In this opportunistic pathogen, subinhibitory levels of polymyxins and certain antimicrobial peptides induce resistance toward higher, otherwise lethal, levels of these antimicrobial agents. It is known that the modification of lipid A of lipopolysaccharide (LPS) is a key component of this adaptive peptide resistance, but to date, the regulatory mechanism underlying peptide regulation in\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    has remained elusive. The PhoP-PhoQ and PmrA-PmrB two-component systems, which control this modification under low-Mg\n                    <jats:sup>2+<\/jats:sup>\n                    conditions, do not appear to play a major role in peptide-mediated adaptive resistance, unlike in\n                    <jats:italic>Salmonella<\/jats:italic>\n                    where PhoQ is a peptide sensor. Here we describe the identification and characterization of a novel\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    two-component regulator affecting\n                    <jats:underline>\n                      <jats:underline>p<\/jats:underline>\n                    <\/jats:underline>\n                    olymyxin-\n                    <jats:underline>\n                      <jats:underline>a<\/jats:underline>\n                    <\/jats:underline>\n                    daptive\n                    <jats:underline>\n                      <jats:underline>r<\/jats:underline>\n                    <\/jats:underline>\n                    esistance, ParR-ParS (PA1799-PA1798). This system was required for activation of the\n                    <jats:italic>arnBCADTEF<\/jats:italic>\n                    LPS modification operon in the presence of subinhibitory concentrations of polymyxin, colistin, or the bovine peptide indolicidin, leading to increased resistance to various polycationic antibiotics, including aminoglycosides. This study highlights the complexity of the regulatory network controlling resistance to cationic antibiotics and host peptides in\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    , which has major relevance in the development and deployment of cationic antimicrobials.\n                  <\/jats:p>","DOI":"10.1128\/aac.00242-10","type":"journal-article","created":{"date-parts":[[2010,6,15]],"date-time":"2010-06-15T00:11:20Z","timestamp":1276560680000},"page":"3372-3382","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":317,"title":["Adaptive Resistance to the \u201cLast Hope\u201d Antibiotics Polymyxin B and Colistin in\n                    <i>Pseudomonas aeruginosa<\/i>\n                    Is Mediated by the Novel Two-Component Regulatory System ParR-ParS"],"prefix":"10.1128","volume":"54","author":[{"given":"Luci\u0301a","family":"Ferna\u0301ndez","sequence":"first","affiliation":[{"name":"Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. James","family":"Gooderham","sequence":"additional","affiliation":[{"name":"Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjeet","family":"Bains","sequence":"additional","affiliation":[{"name":"Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph B.","family":"McPhee","sequence":"additional","affiliation":[{"name":"Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irith","family":"Wiegand","sequence":"additional","affiliation":[{"name":"Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E. 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