Kastbjerg Vicky G, Hein-Kristensen Line, Gram Lone
National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.
Department of System Biology, Technical University of Denmark, Kongens Lyngby, Denmark
Antimicrob Agents Chemother. 2014 Jun;58(6):3124-32. doi: 10.1128/AAC.02266-13. Epub 2014 Mar 17.
Exposure of the human food-borne pathogen Listeria monocytogenes to sublethal concentrations of triclosan can cause resistance to several aminoglycosides. Aminoglycoside-resistant isolates exhibit two colony morphologies: normal-size and pinpoint colonies. The purposes of the present study were to characterize the small colonies of L. monocytogenes and to determine if specific genetic changes could explain the triclosan-induced aminoglycoside resistance in both pinpoint and normal-size isolates. Isolates from the pinpoint colonies grew poorly under aerated conditions, but growth was restored by addition of antibiotics. Pinpoint isolates had decreased hemolytic activity under stagnant conditions and a changed spectrum of carbohydrate utilization compared to the wild type and isolates from normal-size colonies. Genome sequence comparison revealed that all seven pinpoint isolates had a mutation in a heme gene, and addition of heme caused the pinpoint isolates to revert to normal colony size. Triclosan-induced gentamicin-resistant isolates had mutations in several different genes, and it cannot be directly concluded how the different mutations caused gentamicin resistance. However, since many of the mutations affected proteins involved in respiration, it seems likely that the mutations affected the active transport of the antibiotic and thereby caused resistance by decreasing the amount of aminoglycoside that enters the bacterial cell. Our study emphasizes that triclosan likely has more targets than just fabI and that exposure to triclosan can cause resistance to antibiotics that enters the cell via active transport. Further studies are needed to elucidate if L. monocytogenes pinpoint isolates could have any clinical impact, e.g., in persistent infections.
将食源性人类病原菌单核细胞增生李斯特菌暴露于亚致死浓度的三氯生中会导致其对几种氨基糖苷类抗生素产生耐药性。耐氨基糖苷类抗生素的分离株呈现出两种菌落形态：正常大小的菌落和针尖状菌落。本研究的目的是对单核细胞增生李斯特菌的小菌落进行特征描述，并确定特定的基因变化是否可以解释三氯生诱导的针尖状和正常大小分离株中的氨基糖苷类抗生素耐药性。从针尖状菌落分离出的菌株在通气条件下生长较差，但添加抗生素后生长得以恢复。与野生型以及从正常大小菌落分离出的菌株相比，针尖状分离株在静止条件下溶血活性降低，碳水化合物利用谱发生改变。基因组序列比较显示，所有七个针尖状分离株在一个血红素基因中都有突变，添加血红素会使针尖状分离株恢复为正常菌落大小。三氯生诱导的庆大霉素耐药分离株在几个不同基因中存在突变，无法直接得出不同突变如何导致庆大霉素耐药性的结论。然而，由于许多突变影响了参与呼吸作用的蛋白质，似乎这些突变影响了抗生素的主动转运，从而通过减少进入细菌细胞的氨基糖苷类抗生素量而导致耐药性。我们的研究强调，三氯生可能具有比fabI更多的靶点，并且暴露于三氯生会导致对通过主动转运进入细胞的抗生素产生耐药性。需要进一步研究以阐明单核细胞增生李斯特菌针尖状分离株是否可能具有任何临床影响，例如在持续性感染中。
