Role of efflux mechanisms on fluoroquinolone resistance in Streptococcus pneumoniae and Pseudomonas aeruginosa

Zhanel, George G.; Hoban, Daryl J.; Schurek, Kristen N.; Karlowsky, James A.

doi:10.1016/j.ijantimicag.2004.08.003

Cited by 48 publications

(37 citation statements)

References 70 publications

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“…The activity of an efflux pump contributes only minimally to FQ resistance in Streptococcus spp. (10,28). In this study, no significant change in the FQ MICs was observed when testing was done in the presence of reserpine.…”

Section: Discussionmentioning

confidence: 55%

Prevalence and Clonal Characterization of Streptococcus pyogenes Clinical Isolates with Reduced Fluoroquinolone Susceptibility in Spain

Montes

Tamayo

Orden

et al. 2010

Antimicrob Agents Chemother

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The aim of this study was to determine the prevalence and characteristics of non-fluoroquinolone (FQ)-susceptible Streptococcus pyogenes isolates and to study their mechanisms of resistance. We performed a prospective prevalence study with 468 isolates collected from 2005 to 2007 and a retrospective study that was based on the examination of existing data collected from 1999 to 2008. The retrospective study included data for isolates with high-level resistance (HR) to ciprofloxacin (MIC > 32 g/ml) (HR isolates) and isolates with the same emm types as those reported in the literature with low-level resistance (LR) to ciprofloxacin (MICs, 2 to 8 g/ml) (LR isolates, n ‫؍‬ 205). Genetic characterization of the isolates was performed by means of emm typing and multilocus sequence typing. The prevalence of LR ranged from 1.9% in 2005 to 30.8% in 2007. This increase was mainly due to the circulation of an emm6 subtype (emm6.4) that represented 77.1% of the LR isolates in 2007. Notably, another emm6 subtype, also detected in 2007 (emm6.37), showed coresistance to 14-and 15-membered macrolides mediated by the mefA gene. Only three HR isolates were detected (isolates emm68.1/ST247/T3,13,B3264, emm77/ST399/T28, and emm28/ST52/T28), and all were identified in the retrospective study. Overall, the 673 isolates represented 25 emm types. All LR isolates were clustered into two emm types: emm6 (six emm6 subtypes) and emm75. All the 156 emm6 isolates had LR, harbored the Ser79/Ala mutation in the parC gene product, and had the same sequence type (ST), ST382. Most (21/33) of the emm75 isolates had LR, showed the Ser79/Phe plus Asp91/Asn double mutation in the parC gene product, and were ST150. The Asp91/Asn mutation by itself did not confer resistance to FQs.

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Section: Discussionmentioning

confidence: 55%

Prevalence and Clonal Characterization of Streptococcus pyogenes Clinical Isolates with Reduced Fluoroquinolone Susceptibility in Spain

Montes

Tamayo

Orden

et al. 2010

Antimicrob Agents Chemother

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“…While active efflux accounts for only a moderate increase in resistance (31), effluxpositive strains exhibit an increased likelihood of acquiring QRDR mutations, and the combination of efflux and first-step mutations can lead to MICs associated with treatment failure (32). To date, two efflux systems have been found to confer resistance to fluoroquinolones on S. pneumoniae.…”

mentioning

confidence: 99%

Genomic Characterization of Ciprofloxacin Resistance in a Laboratory-Derived Mutant and a Clinical Isolate of Streptococcus pneumoniae

Lupien

Billal

Fani

et al. 2013

Antimicrob Agents Chemother

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The broad-spectrum fluoroquinolone ciprofloxacin is a bactericidal antibiotic targeting DNA topoisomerase IV and DNA gyrase encoded by the parC and gyrA genes. Resistance to ciprofloxacin in Streptococcus pneumoniae mainly occurs through the acquisition of mutations in the quinolone resistance-determining region (QRDR) of the ParC and GyrA targets. A role in low-level ciprofloxacin resistance has also been attributed to efflux systems. To look into ciprofloxacin resistance at a genome-wide scale and to discover additional mutations implicated in resistance, we performed whole-genome sequencing of an S. pneumoniae isolate selected for resistance to ciprofloxacin in vitro (128 g/ml) and of a clinical isolate displaying low-level ciprofloxacin resistance (2 g/ml). Gene disruption and DNA transformation experiments with PCR fragments harboring the mutations identified in the in vitro S. pneumoniae mutant revealed that resistance is mainly due to QRDR mutations in parC and gyrA and to the overexpression of the ABC transporters PatA and PatB. In contrast, no QRDR mutations were identified in the genome of the S. pneumoniae clinical isolate with low-level resistance to ciprofloxacin. Assays performed in the presence of the efflux pump inhibitor reserpine suggested that resistance is likely mediated by efflux. Interestingly, the genome sequence of this clinical isolate also revealed mutations in the coding region of patA and patB that we implicated in resistance. Finally, a mutation in the NAD(P)H-dependent glycerol-3-phosphate dehydrogenase identified in the S. pneumoniae clinical strain was shown to protect against ciprofloxacin-mediated reactive oxygen species. Streptococcus pneumoniae is a major Gram-positive pathogen responsible for pneumonia, bacteremia, otitis media, and meningitis leading to considerable morbidity and mortality among children and elderly individuals (1). Penicillin, a ␤-lactam antibiotic, has long been the mainstay against pneumococcal infections (2, 3), but the worldwide spread of antibiotic-resistant clones over the past decades has impaired its usefulness for dealing with S. pneumoniae infections (4-6). The rates of resistance against ␤-lactams and macrolides among S. pneumoniae isolates have translated into an increased usage of fluoroquinolone antibiotics in the treatment of respiratory diseases (7-10).Fluoroquinolones are part of a class of synthetic broad-spectrum antibiotics that inhibit DNA synthesis in bacteria by targeting DNA gyrase (GyrA and -B subunits) and topoisomerase IV (ParC and -E subunits), two enzymes that are vital for DNA supercoiling and chromosome segregation, respectively (11,12). Although the worldwide prevalence of fluoroquinolone-resistant S. pneumoniae remains low in relation to ␤-lactam resistance (Յ1%) (13-15), the dissemination of successful resistant clones has nonetheless increased the prevalence in some countries (16,17). Resistance to fluoroquinolones in S. pneumoniae arises in a stepwise fashion and results from alterations in the target binding site due to...

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“…Other mechanisms such as mutations in the B subunit of DNA gyrase, decreased cell permeability to the drug, and an active drug efflux pump mechanism could also be involved in triggering resistance. In particular, the expression or overexpression of energy-dependent efflux pumps that can actively remove antibacterial agents from the cell have been shown to play a role in determination of FQ resistance [74][75][76] TB rather than becoming the workhorse of antimicrobial treatment; however, given the current widespread use of quinolones this might not be realistic. Lately, the interest on FQs as anti-TB agent has focused on the new FQs moxifloxacin and gatifloxacin.…”

Section: Quinolones and Fluoroquinolonesmentioning

confidence: 99%

Role of quinolones and quinoxaline derivatives in the advancement of treatment of tuberculosis

Asif

2015

IJSW

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The need of new chemotherapeutic drugs to improve tuberculosis control and treatment particularly against multidrugresistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium. The atitubercular drugs are used in current chemotherapy have different chemical moieties. In this review, we provide an overview of the quinolone drugs as an antitubercular drug. Generally quinolone drugs are mainly used against many gram-positive and gram-negative bacterial infections including resistance strains also. Various quinolones are being used to control and treatment of tubercular infections including MDR, XDR and atypical Mycobacterium strains. Fluoroquinolones are an important quinolones, especially for strains that are resistant to first-line agents.

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Role of efflux mechanisms on fluoroquinolone resistance in Streptococcus pneumoniae and Pseudomonas aeruginosa

Cited by 48 publications

References 70 publications

Prevalence and Clonal Characterization of Streptococcus pyogenes Clinical Isolates with Reduced Fluoroquinolone Susceptibility in Spain

Prevalence and Clonal Characterization of Streptococcus pyogenes Clinical Isolates with Reduced Fluoroquinolone Susceptibility in Spain

Genomic Characterization of Ciprofloxacin Resistance in a Laboratory-Derived Mutant and a Clinical Isolate of Streptococcus pneumoniae

Role of quinolones and quinoxaline derivatives in the advancement of treatment of tuberculosis

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