{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:53:52Z","timestamp":1790801632986,"version":"4.1.0"},"reference-count":74,"publisher":"Microbiology Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,1]]},"abstract":"<jats:p><jats:italic>Pseudomonas aeruginosa<\/jats:italic>is one of the most dreaded opportunistic pathogens accounting for 10\u200a% of hospital-acquired infections, with a 50\u200a% mortality rate in chronically ill patients. The increased prevalence of drug-resistant isolates is a major cause of concern. Resistance in<jats:italic>P. aeruginosa<\/jats:italic>is mediated by various mechanisms, some of which are shared among different classes of antibiotics and which raise the possibility of cross-resistance. The goal of this study was to explore the effect of subinhibitory concentrations (SICs) of clinically relevant antibiotics and the role of a global antibiotic resistance and virulence regulator, AmpR, in developing cross-resistance. We investigated the induction of transient cross-resistance in<jats:italic>P. aeruginosa<\/jats:italic>PAO1 upon exposure to SICs of antibiotics. Pre-exposure to carbapenems, specifically imipenem, even at 3 ng ml<jats:sup>\u22121<\/jats:sup>, adversely affected the efficacy of clinically used penicillins and cephalosporins. The high \u03b2-lactam resistance was due to elevated expression of both<jats:italic>ampC<\/jats:italic>and<jats:italic>ampR<\/jats:italic>, encoding a chromosomal \u03b2-lactamase and its regulator, respectively. Differences in the susceptibility of<jats:italic>ampR<\/jats:italic>and<jats:italic>ampC<\/jats:italic>mutants suggested non-AmpC-mediated regulation of \u03b2-lactam resistance by AmpR. The increased susceptibility of<jats:italic>P. aeruginosa<\/jats:italic>in the absence of<jats:italic>ampR<\/jats:italic>to various antibiotics upon SIC exposure suggests that AmpR plays a major role in the cross-resistance. AmpR was shown previously to be involved in resistance to quinolones by regulating MexEF\u2013OprN efflux pump. The data here further indicate the role of AmpR in cross-resistance between quinolones and aminoglycosides. This was confirmed using quantitative PCR, where expression of the<jats:italic>mexEF<\/jats:italic>efflux pump was further induced by ciprofloxacin and tobramycin, its substrate and a non-substrate, respectively, in the absence of<jats:italic>ampR<\/jats:italic>. The data presented here highlight the intricate cross-regulation of antibiotic resistance pathways at SICs of antibiotics and the need for careful assessment of the order of antibiotic regimens as this may have dire consequences. Targeting a global regulator such as AmpR that connects diverse pathways is a feasible therapeutic approach to combat<jats:italic>P. aeruginosa<\/jats:italic>pathogenesis.<\/jats:p>","DOI":"10.1099\/jmm.0.070185-0","type":"journal-article","created":{"date-parts":[[2014,1,26]],"date-time":"2014-01-26T01:40:31Z","timestamp":1390700431000},"page":"544-555","source":"Crossref","is-referenced-by-count":40,"title":["Role of Pseudomonas aeruginosa AmpR on \u03b2-lactam and non-\u03b2-lactam transient cross-resistance upon pre-exposure to subinhibitory concentrations of antibiotics"],"prefix":"10.1099","volume":"63","author":[{"given":"Hansi","family":"Kumari","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Department of Biological 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