Haenni Marisa, Bour Maxime, Châtre Pierre, Madec Jean-Yves, Plésiat Patrick, Jeannot Katy
Unité Antibiorésistance et Virulence Bactériennes, ANSES-Université de LyonLyon, France.
Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire de BesançonBesançon, France.
Front Microbiol. 2017 Sep 29;8:1847. doi: 10.3389/fmicb.2017.01847. eCollection 2017.
Carbapenems are major antibiotics reserved to human medicine. This study aimed to investigate the mechanisms of carbapenem resistance of a selection of veterinary strains from the French network Resapath. Thirty (5.7%) imipenem and/or meropenem non-susceptible of canine ( = 24), feline ( = 5), or bovine ( = 1) origin were identified in a large collection of 527 veterinary strains gathered by the Resapath. These resistant isolates belonged to 25 MultiLocus Sequence Types (MLST), of which 17 (68%) are shared with clinical (human) strains, such as high risk clones ST233 and ST395. Interestingly, none of the veterinary strains produced a carbapenemase, and only six of them (20%) harbored deletions or insertion sequence (IS) disrupting the porin OprD gene. The remaining 24 strains contained mutations or IS in various loci resulting in down-regulation of gene coupled with upregulation of efflux system CzcCBA ( = 3; activation of sensor kinase CzcS ± CopS), MexEF-OprN ( = 4; alteration of oxido reductase MexS), MexXY ( = 8; activation of two-component system ParRS), or MexAB-OprM ( = 12; alteration of regulator MexR, NalC ± NalD). Two efflux pumps were co-produced simultaneously in three mutants. Finally, in 11 out of 12 strains displaying an intact porin OprD, derepression of MexAB-OprM accounted for a decreased susceptibility to meropenem relative to imipenem. Though not treated by carbapenems, animals thus represent a reservoir of multidrug resistant strains potentially able to contaminate fragile outpatients.
碳青霉烯类是主要用于人类医学的抗生素。本研究旨在调查从法国Resapath网络选取的一批兽医菌株对碳青霉烯类耐药的机制。在Resapath收集的527株兽医菌株中,鉴定出30株(5.7%)对亚胺培南和/或美罗培南不敏感,这些菌株来自犬类(n = 24)、猫类(n = 5)或牛类(n = 1)。这些耐药菌株属于25种多位点序列类型(MLST),其中17种(68%)与临床(人类)菌株相同,如高风险克隆ST233和ST395。有趣的是,没有一株兽医菌株产生碳青霉烯酶,只有6株(20%)携带导致孔蛋白OprD基因缺失或插入序列(IS)。其余24株在不同位点含有突变或IS,导致基因下调,同时外排系统CzcCBA(n = 3;传感器激酶CzcS±CopS激活)、MexEF - OprN(n = 4;氧化还原酶MexS改变)、MexXY(n = 8;双组分系统ParRS激活)或MexAB - OprM(n = 12;调节子MexR改变,NalC±NalD)上调。三个突变体同时共产生两种外排泵。最后,在12株孔蛋白OprD完整的菌株中,有11株MexAB - OprM的去阻遏导致对美罗培南的敏感性相对于亚胺培南降低。因此,尽管动物未接受碳青霉烯类治疗,但它们是多药耐药菌株的储存库,有可能污染脆弱的门诊患者。