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Braz. j. microbiol ; 47(4): 925-930, Oct.-Dec. 2016. tab
Artigo em Inglês | LILACS | ID: biblio-828207


Abstract The aim of this study was to examine mutations in the quinolone-resistance-determining region (QRDR) of gyrA and parC genes in Pseudomonas aeruginosa isolates. A total of 100 clinical P. aeruginosa isolates were collected from different university-affiliated hospitals in Tabriz, Iran. Minimum inhibitory concentrations (MICs) of ciprofloxacin and levofloxacin were evaluated by agar dilution assay. DNA sequences of the QRDR of gyrA and parC were determined by the dideoxy chain termination method. Of the total 100 isolates, 64 were resistant to ciprofloxacin. No amino acid alterations were detected in gyrA or parC genes of the ciprofloxacin susceptible or ciprofloxacin intermediate isolates. Thr-83 → Ile substitution in gyrA was found in all 64 ciprofloxacin resistant isolates. Forty-four (68.75%) of them had additional substitution in parC. A correlation was found between the number of the amino acid alterations in the QRDR of gyrA and parC and the level of ciprofloxacin and levofloxacin resistance of the P. aeruginosa isolates. Ala-88 → Pro alteration in parC was generally found in high level ciprofloxacin resistant isolates, which were suggested to be responsible for fluoroquinolone resistance. These findings showed that in P. aeruginosa, gyrA was the primary target for fluoroquinolone and additional mutation in parC led to highly resistant isolates.

Humanos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/epidemiologia , Fluoroquinolonas/farmacologia , DNA Girase/genética , DNA Topoisomerase IV/genética , Farmacorresistência Bacteriana , Mutação , Pseudomonas aeruginosa/isolamento & purificação , Testes de Sensibilidade Microbiana , Análise de Sequência de DNA , Irã (Geográfico)/epidemiologia , Antibacterianos/farmacologia
Rev. chil. infectol ; 32(5): 499-504, oct. 2015. tab
Artigo em Espanhol | LILACS | ID: lil-771616


Quinolones are a family of synthetic broad-spectrum antimicrobial drugs whose target is the synthesis of DNA. They directly inhibit DNA replication by interacting with two enzymes; DNA gyrase and topoisomerase IV. They have been widely used for the treatment of several community and hospital acquired infections, in the food processing industry and in the agricultural field, making the increasing incidence of quinolone resistance a frequent problem associated with constant exposition to diverse microorganisms. Resistance may be achieved by three non-exclusive mechanisms; through chromosomic mutations in the Quinolone Resistance-Determining Regions of DNA gyrase and topoisomerase IV, by reducing the intracytoplasmic concentrations of quinolones actively or passively and by Plasmid-Mediated Quinolones-Resistance genes, [Qnr determinant genes of resistance to quinolones, variant gene of the aminoglycoside acetyltransferase (AAC(6')-Ib-c)] and encoding genes of efflux pumps (qepA and oqxAB)]. The future of quinolones is uncertain, however, meanwhile they continue to be used in an irrational way, increasing resistance to quinolones should remain as an area of primary priority for research.

Las quinolonas son un grupo de antimicrobianos sintéticos de amplio espectro, cuyo objetivo es la síntesis del ADN. Inhiben directamente su replicación al interactuar con dos enzimas; ADN girasa y topoisomerasa IV. Se han utilizado ampliamente para el tratamiento de infecciones intra y extra-hospitalarias, en el campo de la agricultura y en el procesamiento de alimentos, lo que hace que el incremento de resistencia a quinolonas sea un problema cada vez más frecuente, asociado a la constante exposición de diversos microorganismos. La resistencia puede alcanzarse mediante tres mecanismos no excluyentes entre sí; a través de mutaciones cromosómicas en genes codificantes que afectan las regiones determinantes de resistencia a quinolonas de ADN girasa y topoisomerasa IV, al reducir las concentraciones intracitoplásmicas de quinolonas de manera activa o pasiva y por genes de resistencia a quinolonas mediados por plásmidos [genes de resistencia a quinolonas determinates de qnr, gen variante de la aminoglucósido acetil transferasa (AAC(6’)-lb-cr) y genes codificadores de bombas de eflujo (qepAy oqxAB)]. El futuro de las quinolonas es incierto; sin embargo, mientras continúen empleándose para el manejo de infecciones en el ser humano, el incremento de resistencia a quinolonas debe permanecer como un área de importancia primaria para la investigación.

Humanos , Antibacterianos/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Quinolonas/farmacologia , Acetiltransferases/genética , DNA Girase/genética , DNA Topoisomerase IV/genética , Farmacorresistência Bacteriana/genética , Enterobacteriaceae/enzimologia , Enterobacteriaceae/genética
Braz. j. microbiol ; 46(3): 753-757, July-Sept. 2015. tab, ilus
Artigo em Inglês | LILACS | ID: lil-755797


Quinolones and fluoroquinolones are widely used to treat uropathogenic Escherichia coli infections. Bacterial resistance to these antimicrobials primarily involves mutations in gyrA and parC genes. To date, no studies have examined the potential relationship between biochemical characteristics and quinolone resistance in uropathogenic E. coli strains. The present work analyzed the quinolone sensitivity and biochemical activities of fifty-eight lactose-negative uropathogenic E. coli strains. A high percentage of the isolates (48.3%) was found to be resistant to at least one of the tested quinolones, and DNA sequencing revealed quinolone resistant determining region gyrA and parC mutations in the multi-resistant isolates. Statistical analyses suggested that the lack of ornithine decarboxylase (ODC) activity is correlated with quinolone resistance. Despite the low number of isolates examined, this is the first study correlating these characteristics in lactose-negative E. coli isolates.


Humanos , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Escherichia coli/tratamento farmacológico , Fluoroquinolonas/uso terapêutico , Lactose/metabolismo , Ácido Nalidíxico/uso terapêutico , Ornitina Descarboxilase/genética , Infecções Urinárias/tratamento farmacológico , Escherichia coli Uropatogênica/genética , Antibacterianos/uso terapêutico , Brasil , DNA Girase/genética , DNA Topoisomerase IV/genética , Descarboxilação/genética , Descarboxilação/fisiologia , Infecções por Escherichia coli/microbiologia , Testes de Sensibilidade Microbiana , Ornitina/metabolismo , Infecções Urinárias/microbiologia , Escherichia coli Uropatogênica/efeitos dos fármacos , Escherichia coli Uropatogênica/enzimologia , Escherichia coli Uropatogênica/isolamento & purificação
Braz. j. microbiol ; 45(1): 239-242, 2014. tab
Artigo em Inglês | LILACS | ID: lil-709485


To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH) clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs) of DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 MH isolates with three kinds of quinolone resistance phenotypes were obtained. Thirteen out of these quinolone-resistant isolates were found to carry nucleotide substitutions in either gyrA or parC. There were no alterations in gyrB and no mutations were found in the isolates with a phenotype of resistance to Ofloxacin (OFX), intermediate resistant to Levofloxacin (LVX) and Sparfloxacin (SFX), and those susceptible to all three tested antibiotics. The molecular mechanism of fluoroquinolone resistance in clinical isolates of MH was reported in this study. The single amino acid mutation in ParC of MH may relate to the resistance to OFX and LVX and the high-level resistance to fluoroquinolones for MH is likely associated with mutations in both DNA gyrase and the ParC subunit of topoisomerase IV.

Humanos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Fluoroquinolonas/farmacologia , Mutação de Sentido Incorreto , Infecções por Mycoplasma/microbiologia , Mycoplasma hominis/efeitos dos fármacos , Infecções do Sistema Genital/microbiologia , DNA Girase/genética , DNA Topoisomerase IV/genética , Mycoplasma hominis/genética , Mycoplasma hominis/isolamento & purificação
Braz. j. infect. dis ; 17(4): 431-437, July-Aug. 2013. ilus, tab
Artigo em Inglês | LILACS | ID: lil-683130


OBJECTIVES: To study the potential factors include gene mutation, efflux pump and alteration of permeability associated with quinolone-resistance of Salmonella enterica strains isolated from patients with acute gastroenteritis and to evaluate the degree of synergistic activity of efflux pump inhibitors when combined with ciprofloxacin against resistant isolates. METHODS: Antimicrobial resistance patterns of fifty-eight Salmonella isolates were tested. Five isolates were selected to study the mechanism of resistance associated with quinolone group, including mutation in topoisomerase-encoding gene, altered cell permeability, and expression of an active efflux system. In addition, the combination between antibiotics and efflux pump inhibitors to overcome the microbial resistance was evaluated. RESULTS: Five Salmonella isolates totally resistant to all quinolones were studied. All isolates showed alterations in outer membrane proteins including disappearance of some or all of these proteins (Omp-A, Omp-C, Omp-D and Omp-F). Minimum inhibitory concentration values of ciprofloxacin were determined in the presence/absence of the efflux pump inhibitors: carbonyl cyanide m-chlorophenylhydrazone, norepinephrin and trimethoprim. Minimum inhibitory concentration values for two of the isolates were 2-4 fold lower with the addition of efflux pump inhibitors. All five Salmonella isolates were amplified for gyrA and parC genes and only two isolates were sequenced. S. Enteritidis 22 had double mutations at codon 83 and 87 in addition to three mutations at parC at codons 67, 76 and 80 whereas S. Typhimurium 57 had three mutations at codons 83, 87 and 119, but no mutations at parC. CONCLUSIONS: Efflux pump inhibitors may inhibit the major AcrAB-TolC in Salmonella efflux systems which are the major efflux pumps responsible for multidrug resistance in Gramnegative clinical isolates.

Humanos , Antibacterianos/farmacologia , Fluoroquinolonas/farmacologia , Salmonella enterica/efeitos dos fármacos , DNA Girase/genética , DNA Topoisomerase IV/genética , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Salmonella enterica/genética , Salmonella enterica/isolamento & purificação
Mem. Inst. Oswaldo Cruz ; 107(5): 687-689, Aug. 2012. tab
Artigo em Inglês | LILACS | ID: lil-643757


In this study, we investigated the presence of plasmid-mediated quinolone resistance (PMQR) genes among 101 ciprofloxacin-resistant urinary Escherichia coli isolates and searched for mutations in the quinolone-resistance-determining regions (QRDRs) of the DNA gyrase and topoisomerase IV genes in PMQR-carrying isolates. Eight isolates harboured the qnr and aac(6')-Ib-cr genes (3 qnrS1, 1 qnrB19 and 4 aac(6')-Ib-cr). A mutational analysis of the QRDRs in qnr and aac(6')-Ib-cr-positive isolates revealed mutations in gyrA, parC and parE that might be associated with high levels of resistance to quinolones. No mutation was detected in gyrB. Rare gyrA, parC and parE mutations were detected outside of the QRDRs. This is the first report of qnrB19, qnrS1 and aac(6')-Ib-cr -carrying E. coli isolates in Brazil.

Feminino , Humanos , Acetiltransferases/genética , Antibacterianos/farmacologia , Ciprofloxacino/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Proteínas de Escherichia coli/genética , Escherichia coli/genética , DNA Girase , DNA Topoisomerase IV , Eletroforese em Gel de Campo Pulsado , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Mutação , Quinolonas/farmacologia