Genomic and phenotypic characterisation of fluoroquinolone resistance mechanisms in Enterobacteriaceae in Durban, South Africa

• Published in: PloS one 2017-06, Vol.12 (6), p.e0178888-e0178888
• Main Authors: Osei Sekyere, John, Amoako, Daniel Gyamfi
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Antibiotics; Bacteria; Bacterial infections; Bacterial Proteins - genetics; Biology and Life Sciences; Carbonyls; Citrobacter; Complications and side effects; Cyanides; Disease transmission; DNA topoisomerase; DNA topoisomerase IV; Dosage and administration; Drug Resistance, Bacterial - genetics; E coli; Efflux; Enterobacteriaceae; Enterobacteriaceae - drug effects; Enterobacteriaceae - genetics; Enterobacteriaceae - isolation & purification; Enterobacteriaceae Infections - microbiology; Epidemiology; Fluoroquinolones; Fluoroquinolones - pharmacology; Genes; Genetic aspects; Genomes; Genomics - methods; Health sciences; Hospitals; Humans; Hydrazine; Klebsiella; Medicine and Health Sciences; Microbial drug resistance; Microbial Sensitivity Tests; Mutation; Pharmaceutical sciences; Phenotype; Physiological aspects; Plasmids; Pneumonia; Pumps; Reserpine; Salmonella; South Africa; Staphylococcus infections; Studies; Transcription; Transposons; Verapamil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0178888

Resistance to fluoroquinolones (FQ) is being increasingly reported and found to be mediated by efflux pumps, plasmid-mediated quinolone resistance genes (PMQR) and mutations in gyrA, gyrB, parC and parE. However, studies reporting on FQ resistance mechanisms (FQRM), particularly in Africa, are focused mostly on Salmonella. This study used a whole-genome-based approach to describe FQRM in forty-eight clinical Enterobacteriaceae isolates comprising of Klebsiella pneumoniae (n = 21), Serratia marcescens (n = 12), Enterobacter spp. (n = 10), Citrobacter freundii (n = 3), Escherichia coli (n = 1), and Klebsiella michiganensis (n = 1) with reduced susceptibility to FQ in Enterobacteriaceae. All the isolates exhibited exceptionally high-level resistance (MIC of 4-512mg/L) to all three FQs, which could not be reversed by carbonyl cyanide m-chlorophenyl hydrazine (CCCP), verapamil (VRP) or reserpine (RSP). PMQR genes such as oqxAB (n = 43), aac(6')-Ib-cr (n = 28), and qnr(S1, B1, B2, B9, B49, B66) (n = 23) were identified without transposons or integrons in their immediate environments. Multiple and diverse mutations were found in gyrA (including S83I/Y and T/I83I/T), gyrB, parC and parE, which were clonally specific. There were vertical and horizontal transmission of high-level FQ resistance in Enterobacteriaceae in hospitals in Durban, South Africa, which are mediated by efflux, PMQR genes, and gyrA, gyrB, parC and parE mutations.