Alteration of GyrA Amino Acid Required for Ciprofloxacin Resistance in Klebsiella pneumoniae Isolates in China

Abstract

Resistance to ciprofloxacin was detected in 111 (48.1%) isolates of Klebsiella pneumoniae from China. GyrA alterations were identified in the ciprofloxacin-resistant and ciprofloxacin-susceptible isolates. The results, including previously published data, indicate that the single substitution Ser833Ile and three types of double mutations at Ser83 and Asp87 were required for ciprofloxacin resistance (P < 0.05).Resistance to fluoroquinolones is increasing in Klebsiella pneumoniae strains. Mechanisms of resistance to fluoroquinolones in the Enterobacteriaceae have been shown to be due primarily to alterations in gyrA, which encodes DNA gyrase, a type II topoisomerase (1, 4). The mutations are localized in an area named as the quinolone resistance-determining region (QRDR) (24). DNA sequencing of the GyrA QRDR in clinical isolates showed some alterations associated with fluoroquinolone resistance in K. pneumoniae (8,11,24).In this paper, 231 consecutive, nonrepetitive isolates of K.

Characterization of Klebsiella pneumoniae associated with cattle infections in southwest China using multi-locus sequence typing (MLST), antibiotic resistance and virulence-associated gene profile analysis

“…Several reports have shown5, 6 that changes in the structure of the QRDRs in gyrA and parC are one of the significant mechanisms in conferring a resistance to fluoroquinolone in gram negative bacilli. The mutations of Ser83 with Phe, Ile, Tyr and Leu is frequently displayed in K. pneumoniae in some studies 5, 30. However, the results from this study suggested the mainly existence of Ser83-Thr alteration in K. pneumoniae isolates, which may be simply due to the investigation of a new population, since most reports have focused on human clinical isolates or bovine mastitis.…”

“…The mutations of Ser83 with Phe, Ile, Tyr and Leu is frequently displayed in K. pneumoniae in some studies. 5 , 30 However, the results from this study suggested the mainly existence of Ser83-Thr alteration in K. pneumoniae isolates, which may be simply due to the investigation of a new population, since most reports have focused on human clinical isolates or bovine mastitis. In this study, it was found that in the Ciprofloxacin-resistant K. pneumoniae , the mutation of the 80th site in the bacterial parC gene was commonly accompanied by the mutation of the gyrA gene, and when parC gene and gyrA gene mutated the sites together, the Ciprofloxacin-resistance rate increased significantly, the results indicating that mutations of parC gene and gyrA gene will make K. pneumoniae more highly resistant to Ciprofloxacin.…”

Comparative analysis of the complete genome of KPC-2-producing Klebsiella pneumoniae Kp13 reveals remarkable genome plasticity and a wide repertoire of virulence and resistance mechanisms

“…Mutations in specific sites in genes coding for proteins used as targets for antimicrobials, such as GyrA and ParC, can result in decreased drug sensitivity. Kp13 showed the double substitutions Ser83 → Phe and Asp87 → Asn in GyrA (KP00955) which are known to confer ciprofloxacin resistance [ 50 ]. Also, a single amino acid change, Ser80 → Ile, was detected in ParC (KP02784), and the combined effect of these mutations could have contributed to the high-level resistance to quinolones displayed by Kp13 as has been shown for other pathogenic bacteria [ 51 ].…”

Sequencing and Genetic Variation of Multidrug Resistance Plasmids in Klebsiella pneumoniae

“…In K. pneumoniae isolates, point mutations in DNA gyrase A (GyrA), plasmid partition protein (ParC), or multidrug efflux pump (AcrA) may be associated with fluoroquinolone resistance [22] , [23] , [24] . In this study, we systematically investigated single nucleotide substitutions in three plasmids from 206 clinical isolates, and found a large amount of nonsynonymous mutations.…”