Karatzas Kimon A G, Webber Mark A, Jorgensen Frieda, Woodward Martin J, Piddock Laura J V, Humphrey Tom J
Zoonotic Infections Group, Division of Veterinary Pathology, Infection and Immunity, School of Clinical Veterinary Science, University of Bristol, Langford House, Langford, Bristol BS40 5DU, UK.
J Antimicrob Chemother. 2007 Nov;60(5):947-55. doi: 10.1093/jac/dkm314. Epub 2007 Sep 13.
To study how disinfectants affect antimicrobial susceptibility and phenotype of Salmonella enterica serovar Typhimurium SL1,344.
Wild-type strain SL1,344 and its isogenic gyrA mutant were passaged daily for 7 days in subinhibitory concentrations, and separately for 16 days in gradually increasing concentrations of a quaternary ammonium disinfectant containing formaldehyde and glutaraldehyde (QACFG), an oxidizing compound blend (OXC), a phenolic tar acids-based disinfectant (TOP) and triclosan. The MICs of antimicrobials and antibiotics for populations and representative isolates and the proportion of cells resistant to the MICs for the wild-type were determined. Expression of acrB gene, growth at 37 degrees C and invasiveness of populations in Caco-2 intestinal epithelial cells were assessed.
QACFG and triclosan showed the highest selectivity for variants with reduced susceptibility to chloramphenicol, tetracycline, ampicillin, acriflavine and triclosan. Populations treated with the above biocides had reduced invasiveness in Caco-2 cells, and altered growth kinetics. Resistance to disinfectants was observed only after exposure to gradually increasing concentrations of triclosan, accompanied with a 2000-fold increase in its MIC. Growth in OXC and TOP did not affect the MICs of antibiotics, but resulted in the appearance of a proportion of cells resistant to the MIC of acriflavine and triclosan for the wild-type. Randomly selected stable variants from all populations, except the one treated with TOP, over-expressed acrB.
In vitro exposure to QACFG and triclosan selects for Salmonella Typhimurium cells with reduced susceptibility to several antibiotics. This is associated with overexpression of AcrAB efflux pump, but accompanied with reduced invasiveness.
研究消毒剂如何影响肠炎沙门氏菌鼠伤寒血清型SL1,344的抗菌敏感性和表型。
野生型菌株SL1,344及其同基因gyrA突变体在亚抑菌浓度下每日传代培养7天，并分别在含甲醛和戊二醛的季铵消毒剂（QACFG）、氧化复合剂（OXC）、酚类焦油酸基消毒剂（TOP）和三氯生的浓度逐渐增加的环境中传代培养16天。测定群体和代表性分离株对抗菌剂和抗生素的最低抑菌浓度（MIC）以及野生型对MIC耐药的细胞比例。评估acrB基因的表达、37℃下的生长情况以及群体在Caco-2肠上皮细胞中的侵袭性。
QACFG和三氯生对氯霉素、四环素、氨苄青霉素、吖啶黄素和三氯生敏感性降低的变体表现出最高的选择性。用上述杀菌剂处理的群体在Caco-2细胞中的侵袭性降低，且生长动力学发生改变。仅在暴露于浓度逐渐增加的三氯生后才观察到对消毒剂的耐药性，同时其MIC增加了2000倍。在OXC和TOP中生长不影响抗生素的MIC，但导致野生型中出现一定比例对吖啶黄素和三氯生的MIC耐药的细胞。除用TOP处理的群体外，从所有群体中随机选择的稳定变体均过表达acrB。
体外暴露于QACFG和三氯生会选择出对多种抗生素敏感性降低的鼠伤寒沙门氏菌细胞。这与AcrAB外排泵的过表达有关，但伴随着侵袭性降低。
