A molecular analysis of quinolone-resistant Haemophilus influenzae: Validation of the mutations in Quinolone Resistance-Determining Regions

Shoji, Hisashi; Shirakura, Tetsuro; Fukuchi, Kunihiko; Teratani, Takuma; Hanaki, Hideaki; Tanaka, Kazuo; Niki, Yoshihito

doi:10.1016/j.jiac.2013.12.007

Cited by 30 publications

(56 citation statements)

References 21 publications

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“…In the present study, the most common changes in GyrA were Ser84 to Leu or Tyr and Asp88 to Tyr, Asn, or Gly, which have been reported to contribute to resistance in H. influenzae (15,16,18,19,22,29,33,37,39). In ParC, the most common changes were Ser84Ile and Glu88Lys, which have been widely described in the literature (16,18,19,22,29,33,39), and Ser84Arg, a change also reported by other authors as an alteration involved in resistance (15,16,22,24,29,33,39). In addition, our study presents two strains harboring two new previously unidentified ParC changes, Ser84Asn and Ser84Ala.…”

Section: Discussionsupporting

confidence: 50%

“…Some specific mutations involved in FQ resistance in H. influenzae were originally described in 1996 (19). Subsequent studies have confirmed the mutations described by Georgiou et al and described new mutations involved in resistance (15,16,18,19,22,24,29,33,37,39). FQ resistance is acquired gradually with increasing numbers of mutations.…”

Section: Discussionmentioning

confidence: 54%

“…Since its first description in 1993, FQ-resistant H. influenzae has been isolated mainly from elderly patients with chronic lung diseases who received frequent antimicrobial treatments, including quinolones (7,15,16,32 (29). A recent surveillance study published in Taiwan showed a major increase in LVX resistance from 2% in 2004 to 24.3% in 2010 (35).…”

Section: Discussionmentioning

confidence: 99%

“…␤-Lactamase activity was screened for by the chromogenic cephalosporin method (nitrocefin disks; BD, Madrid, Spain). QRDRs were amplified with specific oligonucleotide pairs as described previously (19,29). PCR fragments that included gyrA nucleotides 137 to 546, parC nucleotides 129 to 547, gyrB nucleotides 1094 to 1539, and parE nucleotides 1002 to 1473 were purified with a GeneJET PCR purification kit (Thermo Scientific) and sequenced on both strands with the same oligonucleotides used for the PCRs and an Applied Biosystems 3730 XL DNA analyzer.…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Molecular Characterization of Fluoroquinolone Resistance in Nontypeable Haemophilus influenzae Clinical Isolates

Puig

Tirado-Vélez

Calatayud

et al. 2015

Antimicrob Agents Chemother

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Characterization of Fluoroquinolone Resistance in Nontypeable Haemophilus influenzae Clinical Isolates

Puig

Tirado-Vélez

Calatayud

et al. 2015

Antimicrob Agents Chemother

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“…M acrolide-, ␤-lactam-, and fluoroquinolone-resistant Haemophilus influenzae strains have been isolated worldwide (1)(2)(3)(4). In particular, clarithromycin (CLR)-resistant strains have been increasing in Japan (1).…”

mentioning

confidence: 99%

Amino Acid Substitution in the Major Multidrug Efflux Transporter Protein AcrB Contributes to Low Susceptibility to Azithromycin in Haemophilus influenzae

Seyama

Wajima

Nakaminami

et al. 2017

Antimicrob Agents Chemother

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Clarithromycin-resistant Haemophilus influenzae strains with a nonsense mutation in acrR generally exhibited susceptibility to azithromycin, although one strain was found to be nonsusceptible; we aimed to clarify the differences. This strain had an amino acid substitution, Arg327Ser, in AcrB. Introduction of this substitution into H. influenzae Rd caused an increase in the MIC of azithromycin, suggesting that this substitution contributed to nonsusceptibility. These findings indicate that azithromycin-nonsusceptible isolates could occur through stepwise mutation in the acr region.

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Molecular characterization of fluoroquinolones, macrolides, and imipenem resistance in Haemophilus influenzae: analysis of the mutations in QRDRs and assessment of the extent of the AcrAB-TolC-mediated resistance

Cherkaoui

Gaïa

Baud

et al. 2018

Eur J Clin Microbiol Infect Dis

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The aims of the present study were to characterize the mechanisms of resistance to fluoroquinolones, macrolides, and imipenem in Haemophilus influenzae, to assess the extent of the AcrAB-TolC-mediated resistance, and to define a core genome multilocus sequence typing (cgMLST) scheme for H. influenzae by using whole-genome sequencing. Four amino acid substitutions in GyrA (at Ser84 and Asp88), ParC (at Ser84), and ParE (at Asp420) were found to be closely associated to the MICs. We did not find any amino acid substitution surrounding the three highly conserved amino acid motifs in PBP3 related to imipenem resistance. All the isolates possessed the ermB gene. Carbonyl cyanide m-chlorophenylhydrazone (CCCP) decreased the MIC of imipenem by twofold for FQR-6 and fourfold for GE47 and GE88 strains. For erythromycin, the MICs were decreased by twofold. We found that the six FQR isolates were clustered in two groups. The number of different loci within FQR-1_FQR-3_FQR-5 cluster was 6, while FQR-2 and FQR-4 differed for 21 loci. FQR-1_FQR-3_FQR-5 and FQR-2_FQR-4 clusters were distant among each other and compared to 19 genomes downloaded from NCBI, to 8 strains heteroresistant to imipenem, and to 4 strains monoresistant to ciprofloxacin isolated in Denmark. We confirmed that specific amino acid substitutions in GyrA, ParC, and ParE are implicated in quinolone resistance. Additionally, the degree of resistance is related to the number of these amino acid substitutions. We provide robust evidence that drug efflux is one of the substantial mechanisms of imipenem and erythromycin resistance in H. influenzae.

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A molecular analysis of quinolone-resistant Haemophilus influenzae: Validation of the mutations in Quinolone Resistance-Determining Regions

Cited by 30 publications

References 21 publications

Molecular Characterization of Fluoroquinolone Resistance in Nontypeable Haemophilus influenzae Clinical Isolates

Molecular Characterization of Fluoroquinolone Resistance in Nontypeable Haemophilus influenzae Clinical Isolates

Amino Acid Substitution in the Major Multidrug Efflux Transporter Protein AcrB Contributes to Low Susceptibility to Azithromycin in Haemophilus influenzae

Molecular characterization of fluoroquinolones, macrolides, and imipenem resistance in Haemophilus influenzae: analysis of the mutations in QRDRs and assessment of the extent of the AcrAB-TolC-mediated resistance

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