Osei Sekyere John, Amoako Daniel Gyamfi
Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, KNUST, Kumasi, Ghana.
Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
PLoS One. 2017 Jun 21;12(6):e0178888. doi: 10.1371/journal.pone.0178888. eCollection 2017.
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.
对氟喹诺酮类药物（FQ）的耐药性报道日益增多，发现其由外排泵、质粒介导的喹诺酮耐药基因（PMQR）以及gyrA、gyrB、parC和parE的突变介导。然而，关于FQ耐药机制（FQRM）的研究，尤其是在非洲，大多集中在沙门氏菌上。本研究采用基于全基因组的方法来描述48株临床肠杆菌科分离株中的FQRM，这些分离株包括肺炎克雷伯菌（n = 21）、粘质沙雷氏菌（n = 12）、肠杆菌属（n = 10）、弗氏柠檬酸杆菌（n = 3）、大肠埃希菌（n = 1）和密歇根克雷伯菌（n = 1），它们对肠杆菌科中的FQ敏感性降低。所有分离株对所有三种FQ均表现出极高水平的耐药性（MIC为4 - 512mg/L），羰基氰化物间氯苯腙（CCCP）、维拉帕米（VRP）或利血平（RSP）均无法逆转这种耐药性。在其紧邻环境中未发现转座子或整合子的情况下，鉴定出了PMQR基因，如oqxAB（n = 43）、aac(6')-Ib-cr（n = 28）和qnr(S1、B1、B2、B9、B49、B66)（n = 23）。在gyrA（包括S83I/Y和T/I83I/T）、gyrB、parC和parE中发现了多种不同的突变，这些突变具有克隆特异性。在南非德班的医院中，肠杆菌科细菌中高水平FQ耐药性存在垂直和水平传播，其由外排、PMQR基因以及gyrA、gyrB、parC和parE突变介导。
