In vitro activity of older and newer fluoroquinolones against efflux-mediated high-level ciprofloxacin-resistant Streptococcus pneumoniae

Daporta, Matilde Trigo; Bellido, Juan Luis Muñoz; Guirao, Genoveva Yagiie; Hernández, M. Segovia; Garcı́a-Rodrı́guez, J.A.

doi:10.1016/j.ijantimicag.2004.01.012

Cited by 20 publications

(12 citation statements)

References 9 publications

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“…The amino acid substitution Pro (nonpolar) to Ser (polar, uncharged) at ParE position 454 has been previously described in S. pneumoniae strains with decreased susceptibility to fluoroquinolones (33,34). The role of amino acid substitutions at positions 401 and 402 of the M. synoviae GyrB QRDR in fluoroquinolone resistance still remains to be determined.…”

Section: Discussionmentioning

confidence: 95%

Molecular Characterization of Acquired Enrofloxacin Resistance in Mycoplasma synoviae Field Isolates

Lysnyansky¹,

Gerchman²,

Mikula³

et al. 2013

Antimicrob Agents Chemother

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The in vitro activity of enrofloxacin against 73 Mycoplasma synoviae field strains isolated in Israel and Europe was determined by broth microdilution. Decreased susceptibility to enrofloxacin was identified in 59% of strains, with the MICs ranging from 1 to >16 g/ml. The estimated MIC 50 and MIC 90 values for enrofloxacin were 2 and 8 g/ml, respectively. Moreover, this study showed that 92% of recent Israeli field isolates (2009 to 2011) of M. synoviae have MICs of >2 g/ml to enrofloxacin. Comparison of the quinolone resistance-determining regions (QRDRs) in M. synoviae isolates revealed a clear correlation between the presence of one of the amino acid substitutions Asp79-Asn, Thr80-Ala/Ile, Ser81-Pro, and Asp84-Asn/Tyr/His of the ParC QRDR and decreased susceptibility to enrofloxacin (MIC, >1 g/ml). Amino acid substitutions at positions GyrA 87, GyrB 401/402, and ParE 420/454 were also identified, but there was no clear-cut correlation with susceptibility to enrofloxacin. Comparison of vlhA molecular profiles revealed the presence of 9 different genotypes in the Israeli M. synoviae field isolates and 10 genotypes in the European isolates; only one vlhA genotype (type 4) was identified in both cohorts. Based on results of vlhA molecular typing, several mechanisms for emergence and dissemination of Israeli enrofloxacin-resistant M. synoviae isolates are suggested. Mycoplasma synoviae is an economically important pathogen of poultry, causing respiratory disease and infectious synovitis in chickens and turkeys (1). The severity of clinical manifestations of M. synoviae infection ranges from inapparent to severe and is markedly exacerbated by the presence of other bacterial or viral pathogens. In addition, eggshell apex abnormality (EAA) has been recently described as a novel presentation of M. synoviae infection (2, 3).Antibiotic treatment at the beginning of a disease outbreak is sometimes employed to reduce economic losses caused by clinical outbreaks of M. synoviae. Enrofloxacin (En), a broad-spectrum antibiotic related to the class of fluoroquinolones, has been widely used in many countries for treatment of a variety of poultry diseases, mainly those associated with Escherichia coli and Pasteurella multocida but also avian mycoplasmosis (4). However, in some countries the use of En in poultry is not permitted, mainly due to human health concerns; in the United States, En has been banned for use in poultry since 2005.Fluoroquinolones act by inhibition of DNA replication through the formation of a ternary complex with DNA and the active site of DNA replication enzymes (5). Fluoroquinolone resistance occurs primarily through mutations in the quinolone resistance-determining regions (QRDRs) of the parC and/or gyrA gene (encoding the A subunits of DNA gyrase and topoisomerase IV) or the gyrB and/or parE gene (encoding the B subunits of DNA gyrase and topoisomerase IV). Topoisomerase IV (parC gene) has been suggested to be the primary target of En in M. synoviae, based on in vivo selection of strains with decreased ...

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Section: Discussionmentioning

confidence: 95%

Molecular Characterization of Acquired Enrofloxacin Resistance in Mycoplasma synoviae Field Isolates

Lysnyansky¹,

Gerchman²,

Mikula³

et al. 2013

Antimicrob Agents Chemother

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“…The involvement of efflux systems in drug resistance has been demonstrated for S. pneumoniae (26,110), Staphylococcus aureus (62), S. pyogenes (58), and various enterococci (84). Inhibitors of mammalian MDR transporters, such as reserpine, biricodar (VX-710), and timcodar (VX-853), increase the drug sensitivities of these strains.…”

Section: Streptococcus Pneumoniaementioning

confidence: 99%

Distribution and Physiology of ABC-Type Transporters Contributing to Multidrug Resistance in Bacteria

Lubelski

Konings

Driessen

2007

Microbiol Mol Biol Rev

283

188

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SUMMARY Membrane proteins responsible for the active efflux of structurally and functionally unrelated drugs were first characterized in higher eukaryotes. To date, a vast number of transporters contributing to multidrug resistance (MDR transporters) have been reported for a large variety of organisms. Predictions about the functions of genes in the growing number of sequenced genomes indicate that MDR transporters are ubiquitous in nature. The majority of described MDR transporters in bacteria use ion motive force, while only a few systems have been shown to rely on ATP hydrolysis. However, recent reports on MDR proteins from gram-positive organisms, as well as genome analysis, indicate that the role of ABC-type MDR transporters in bacterial drug resistance might be underestimated. Detailed structural and mechanistic analyses of these proteins can help to understand their molecular mode of action and may eventually lead to the development of new strategies to counteract their actions, thereby increasing the effectiveness of drug-based therapies. This review focuses on recent advances in the analysis of ABC-type MDR transporters in bacteria.

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“…• the selection with NOR, a FQ whose activity can be seriously modified by efflux; • the fact that the three resistant mutants obtained showed the same mutations despite the different MICs for some FQs; and • whilst the MIC increases from the wild-type strain to the firststep mutant are similar for the four FQs tested (8× for NOR, CIP and LEV and 4× for MOX), the second-and third-step mutants increase their MICs mainly for the FQs most affected by efflux in other studies [12].…”

Section: Discussionmentioning

confidence: 70%

“…NOR is a highly hydrophilic FQ and is usually the FQ most affected by efflux pumps [12]. Some efflux pumps have been previously associated with FQ resistance in Brucella.…”

Section: Discussionmentioning

confidence: 99%

Fluoroquinolone-resistant Brucella melitensis mutants obtained in vitro

Lázaro

Rodríguez-Tarazona

Garcı́a-Rodrı́guez

et al. 2009

International Journal of Antimicrobial Agents

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In vitro activity of older and newer fluoroquinolones against efflux-mediated high-level ciprofloxacin-resistant Streptococcus pneumoniae

Cited by 20 publications

References 9 publications

Molecular Characterization of Acquired Enrofloxacin Resistance in Mycoplasma synoviae Field Isolates

Molecular Characterization of Acquired Enrofloxacin Resistance in Mycoplasma synoviae Field Isolates

Distribution and Physiology of ABC-Type Transporters Contributing to Multidrug Resistance in Bacteria

Fluoroquinolone-resistant Brucella melitensis mutants obtained in vitro

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