Predictive Studies Suggest that the Risk for the Selection of Antibiotic Resistance by Biocides Is Likely Low in Stenotrophomonas maltophilia.

Predictive Studies Suggest that the Risk for the Selection of Antibiotic Resistance by Biocides Is Likely Low in Stenotrophomonas maltophilia.
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DOI:
10.1371/journal.pone.0132816
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Hernández A
Hernández A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sánchez MB;Decorosi F;Viti C;Oggioni MR;Martínez JL;Hernández A

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杀生剂不受限制地用于几个目的。其结果是,大量杀菌剂在环境中没有任何控制地释放,这种情况可能会挑战微生物种群动态,包括选择具有抗生素耐药性的细菌。以前的工作表明,三氯生选择嗜麦芽窄食单胞菌耐药突变株,过表达外排泵SmeDEF,并诱导该泵的表达,从而触发瞬时的低水平耐药性。在目前的工作中,我们分析了另外两种常见的杀菌剂,苯扎氯铵和六氯苯是否会引发嗜麦芽窄食单胞菌的抗生素耐药性。生物信息学和生物化学方法表明,苯扎氯铵和六氯苯结合了smeDEF的阻遏物Smet。只有苯扎氯铵才能触发Smed的表达,其在短暂性抗生素耐药中的作用很小。六氯酚筛选的突变体都不具有抗药性。两个苯扎氯铵耐药突变株对抗生素的敏感性降低,生长受到损害。代谢图谱显示,它们在某些二肽的使用上比其亲本菌株更熟练。然后我们可以得出结论,尽管生物信息学预测和生化研究表明六氯苯和苯扎氯铵都应该诱导smeDEF的表达,从而导致暂时的嗜麦芽窄食单胞菌对抗生素的耐药性,但表型分析表明这不是真的。六氯酚抗性突变株不耐药,苯扎氯铵抗性突变株对抗生素的敏感性在生长过程中受到损害,这一事实表明,至少在没有持续的选择压力的情况下,通过这些杀菌剂选择(和固定)嗜麦芽窄食单胞菌耐药突变株的风险可能很低。
Biocides are used without restriction for several purposes. As a consequence, large amounts of biocides are released without any control in the environment, a situation that can challenge the microbial population dynamics, including selection of antibiotic resistant bacteria. Previous work has shown that triclosan selects Stenotrophomonas maltophilia antibiotic resistant mutants overexpressing the efflux pump SmeDEF and induces expression of this pump triggering transient low-level resistance. In the present work we analyze if two other common biocides, benzalkonium chloride and hexachlorophene, trigger antibiotic resistance in S. maltophilia. Bioinformatic and biochemical methods showed that benzalkonium chloride and hexachlorophene bind the repressor of smeDEF, SmeT. Only benzalkonium chloride triggers expression of smeD and its effect in transient antibiotic resistance is minor. None of the hexachlorophene-selected mutants was antibiotic resistant. Two benzalkonium chloride resistant mutants presented reduced susceptibility to antibiotics and were impaired in growth. Metabolic profiling showed they were more proficient than their parental strain in the use of some dipeptides. We can then conclude that although bioinformatic predictions and biochemical studies suggest that both hexachlorophene and benzalkonium chloride should induce smeDEF expression leading to transient S. maltophilia resistance to antibiotics, phenotypic assays showed this not to be true. The facts that hexachlorophene resistant mutants are not antibiotic resistant and that the benzalkonium chloride resistant mutants presenting altered susceptibility to antibiotics were impaired in growth suggests that the risk for the selection (and fixation) of S. maltophilia antibiotic resistant mutants by these biocides is likely low, at least in the absence of constant selection pressure.