Induction of mexCD-oprJ operon for a multidrug efflux pump by disinfectants in wild-type Pseudomonas aeruginosa PAO1

Morita, Yuji; Murata, Takeshi; Mima, Takehiko; Shiota, Sumiko; Kuroda, Teruo; Mizushima, Tohru; Gotoh, Naomasa; Nishino, Takeshi; Tsuchiya, Tomofusa

doi:10.1093/jac/dkg173

Cited by 106 publications

(92 citation statements)

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“…Overexpression of drug efflux systems that confer resistance to particular agents has been observed for the NorA (29) and Mde (28) systems of Staphylococcus aureus, the PmrA and Mef systems of S. pneumoniae (16,22), the Lde pump of Listeria monocytogenes (23), the Bmr (2) and EbrAB (37) systems of Bacillus subtilis, and systems in a number of gram-negative organisms (24,40,42,47,50,51). We have found six transporter genes that were consistently expressed at a higher level in the presence of ciprofloxacin by the multidrug-resistant mutant M22 than by its fluoroquinolone-susceptible parent M4.…”

Section: Discussionmentioning

confidence: 99%

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Involvement of the Putative ATP-Dependent Efflux Proteins PatA and PatB in Fluoroquinolone Resistance of a Multidrug-Resistant Mutant of Streptococcus pneumoniae

Marrer

Schad

Satoh

et al. 2006

Antimicrob Agents Chemother

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The multidrug-resistant mutant Streptococcus pneumoniae M22 constitutively overexpresses two genes (patA and patB) that encode proteins homologous to known efflux proteins belonging to the ABC transporter family. It is shown here that PatA and PatB were strongly induced by quinolone antibiotics and distamycin in fluoroquinolone-sensitive strains. PatA was very important for growth of S. pneumoniae, and it could not be disrupted in strain M22. PatB appeared to control metabolic activity, particularly in amino acid biosynthesis, and it may have a pivotal role in coordination of the response to quinolone antibiotics. The induction of PatA and PatB by antibiotics showed a pattern similar to that exhibited by SP1861, a homologue of ABC-type transporters of choline and other osmoprotectants. A second group of quinolone-induced transporter genes comprising SP1587 and SP0287, which are homologues of, respectively, oxalate/formate antiporters and xanthine or uracil permeases belonging to the major facilitator family, showed a different pattern of induction by other antibiotics. There was no evidence for the involvement of PmrA, the putative proton-dependent multidrug transporter that has been implicated in norfloxacin resistance, in the response to quinolone antibiotics in either the resistant mutant or the fluoroquinolone-sensitive strains.Large epidemiological studies of Streptococcus pneumoniae in clinical infections have associated mutations in the genes encoding gyrase and topoisomerase IV with fluoroquinolone resistance (13, 40). However, resistance to fluoroquinolones can also be mediated by active efflux (5, 9-11, 17, 18, 22, 34, 44, 53). Until recently, the only efflux pump implicated in pneumococcal fluoroquinolone resistance was PmrA (22), but it now appears that there must be other efflux pumps involved in this resistance phenotype (11,45). Multidrug-resistant strain M22, a mutant selected after exposure of S. pneumoniae NCTC 7465 (strain M4) to ciprofloxacin, appeared to have such an efflux-mediated resistance mechanism (46). The mutation frequency of 6.9 ϫ 10 Ϫ8 and stable resistance without antibiotic pressure suggested a mutation in a single gene (46). However, no mutations in the fluoroquinolone resistance-determining regions of the A subunits of DNA gyrase or topoisomerase IV have been detected (36). Strain M22 was at least fourfold more resistant than strain M4 to ciprofloxacin, norfloxacin, acriflavine, ethidium bromide, doxorubicin, tetracycline, erythromycin, and cetrimide. The MICs of clinafloxacin, gatifloxacin, grepafloxacin, levofloxacin, and sitafloxacin were reproducibly twofold higher for strain M22 than for strain M4, but those of moxifloxacin, ofloxacin, sparfloxacin, and chloramphenicol were identical for the two strains. The accumulation of ciprofloxacin, gatifloxacin, and ofloxacin by strain M22 was significantly less than that observed in strain M4, whereas the accumulation of norfloxacin and ethidium was consistently higher than in strain M4. Addition of reserpine increased the uptake...

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Section: Discussionmentioning

confidence: 99%

“…Large epidemiological studies of Streptococcus pneumoniae in clinical infections have associated mutations in the genes encoding gyrase and topoisomerase IV with fluoroquinolone resistance (13,40). However, resistance to fluoroquinolones can also be mediated by active efflux (5, 9-11, 17, 18, 22, 34, 44, 53).…”

mentioning

confidence: 99%

Involvement of the Putative ATP-Dependent Efflux Proteins PatA and PatB in Fluoroquinolone Resistance of a Multidrug-Resistant Mutant of Streptococcus pneumoniae

Marrer

Schad

Satoh

et al. 2006

Antimicrob Agents Chemother

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“…The MexCD-OprJ system is generally not expressed in wild-type strains (465) but is inducible by membrane-damaging agents (see Regulation of Multidrug Efflux Pumps and "Bacterial Stress Responses," below) (466,467). Overproduction of the MexCD-OprJ pump in nfxB mutants causes increased resistance to fluoroquinolones, zwitterionic cephalosporins (cefepime and cefpirome), macrolides, chloramphenicol, and tetracyclines concomitant with hypersusceptibility to aminoglycosides and other ␤-lactams (15,440,465,468).…”

Section: Pseudomonas Aeruginosamentioning

confidence: 99%

“…Elevated frequencies of nfxB mutations are also evident with the inactivation of the DNA oxidative repair system (839). Expression of mexCD-oprJ can be induced by a number of biocides (e.g., chlorhexidine and benzalkonium chloride), dyes (ethidium bromide), and other membrane-damaging agents (detergents, solvents, polymyxin B, and antimicrobial peptides) (466,467). Indeed, mexCD-oprJ shows the greatest transcriptomic response among the genes after exposure of P. aeruginosa to chlorhexidine (840).…”

Section: P Aeruginosa Efflux Pumpsmentioning

confidence: 99%

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

2015

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SUMMARY The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

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“…P.aeruginosa PAO1 suşlarında MexCD-OprJ çoklu ilaç atım pompa indüksiyonunun araştı-rıldığı bir çalışmada MexCD-OprJ'nin önemli dezenfektanlarla indüklendiği gösterilmiştir. Bu sonuçlar dezenfaktanların sık olarak kullanıldı-ğı hastanelerde MexCD-OprJ'nin P.aeruginosa'daki intrensek çoklu ilaç direncinde önemli rol oynadığını göstermiştir (27) . Klinikle ilişkili biosidler MexCD-OprJ'yi indüklediğinden P.aeruginosa'da kullanılan antibiyotiklere direnci de arttırmak-tadır.…”

Section: Mexcd-oprj Atım Pompasıunclassified

Pseudomonas aeruginosa Resistance Mechanisms: Efflux Pump Systems

Terzi¹

2016

Ankem Derg

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Induction of mexCD-oprJ operon for a multidrug efflux pump by disinfectants in wild-type Pseudomonas aeruginosa PAO1

Cited by 106 publications

References 10 publications

Involvement of the Putative ATP-Dependent Efflux Proteins PatA and PatB in Fluoroquinolone Resistance of a Multidrug-Resistant Mutant of Streptococcus pneumoniae

Involvement of the Putative ATP-Dependent Efflux Proteins PatA and PatB in Fluoroquinolone Resistance of a Multidrug-Resistant Mutant of Streptococcus pneumoniae

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

Pseudomonas aeruginosa Resistance Mechanisms: Efflux Pump Systems

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