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

被引：21

作者：

Cherkaoui, Abdessalam ^{[1
]}

Gaia, Nadia ^{[2
]}

Baud, Damien ^{[2
]}

Leo, Stefano ^{[2
]}

Fischer, Adrien ^{[1
]}

Ruppe, Etienne ^{[3
]}

Francois, Patrice ^{[2
]}

Schrenzel, Jacques ^{[1
,2
]}

机构：

[1] Geneva Univ Hosp, Lab Med & Pathol, Dept Genet, Serv Lab Med,Bacteriol Lab, 4 Rue Gabrielle Perret Gentil, CH-1205 Geneva, Switzerland

[2] Geneva Univ Hosp, Div Infect Dis, Genom Res Lab, 4 Rue Gabrielle Perret Gentil, CH-1205 Geneva, Switzerland

[3] Univ Paris Diderot, Hop Bichat, AP HP, Lab Bacteriol,INSERM,IAME,UMR 1137,Sorbonne Paris, F-75018 Paris, France

来源：

EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES | 2018年 / 37卷 / 11期

关键词：

Imipenem; Fluoroquinolone; Macrolide; H; influenzae; CCCP; Whole-genome sequencing; cgMLST; Antibiotic resistance; PENICILLIN-BINDING PROTEIN-3; BETA-LACTAM RESISTANCE; TERM-CARE FACILITY; STAPHYLOCOCCUS-AUREUS; ANTIMICROBIAL RESISTANCE; SURVEILLANCE PROGRAM; TOPOISOMERASE-IV; EFFLUX PUMP; STRAINS; SUSCEPTIBILITY;

D O I：

10.1007/s10096-018-3362-z

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

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.

引用

页码：2201 / 2210

页数：10

共 37 条

[11] Role of the AcrAB-TolC efflux pump in determining susceptibility of role Haemophilus influenzae to the novel peptide deformylase inhibitor LBM415 [J].