消毒剂会使金葡菌产生耐药

海内知己

:Q

10月出版的《微生物学》杂志上的一篇文章认为，用来杀灭环境中细菌的化学药品会让细菌变得更强壮。低浓度的这些化学药品，也称抗微生物剂，会让金黄色葡萄球菌把这些毒性化学物质从它们体内有效清除掉，这样它们有可能会对一些抗生素产生耐药。

抗微生物剂被用在消毒剂和防腐剂中以杀死微生物。通常用来清洗医院和家庭的环境、消毒医疗设备以及手术前的皮肤消毒。抗微生物剂在一定强度下可杀死细菌和其它的微生物。但是，如果使用的量不够，细菌将会继续生存并对治疗产生耐受。

“像金黄色葡萄球菌会制作将多种毒性化学物质泵出细菌体外的蛋白，干扰抗生素对它们的治疗效果。”美国退役军人事物医疗中心的格伦.卡特兹说。“这些能排出毒性化学物质的蛋白泵也可将抗生素从细菌里移出去，使得细菌对这些药物产生耐药。我们对抗微生物剂能否也会使细菌在这些蛋白泵作用下而不会被杀死进行了研究。”

研究人员将从患者血液中提取的金黄色葡萄球菌放到几种低浓度抗微生物剂和染料中，这些抗微生物剂是医院经常用到的。他们发现，变异让这些细菌产生了较正常更多的蛋白泵。

“我们发现，暴露在各种低浓度的抗微生物制剂和染料中造成了细菌耐受变异体的出现。”  卡特兹说。“细菌中蛋白泵的数量增加了。由于这些蛋白泵也能清除细菌里的抗生素，有大量蛋白泵的致病菌对患者就会造成威胁，因为它们对抗生素的耐受力更强。”

假如细菌重复不断地暴露于抗微生物剂中，它们就会对消毒剂和抗生素产生耐受。这些细菌多是产生医院获得性感染的细菌。

“科学家正在尝试研制蛋白泵抑制剂。有效的抑制剂将会降低细菌产生耐受的可能性。”  卡特兹说。“遗憾的是到目前为止一些被评估的抑制剂对各种病原体没有效果，因此它们在预防耐受方面不理想。”

“合理使用抗生素，并且使用不被蛋白泵识别的抗微生物剂将会减少耐药菌株的产生。”  卡特兹说。“换句话说，蛋白泵抑制剂结合抗生素或消毒剂将会减少这些菌株的出现和它们对临床产生的不良影响。”（生物谷Bioon.com）

生物谷推荐原始出处：

Microbiology 154 (2008), 3144-3153; DOI  10.1099/mic.0.2008/021188-0

Multidrug efflux pump overexpression in Staphylococcus aureus after single and multiple in vitro exposures to biocides and dyes

Aurélie A. Huet1,3, Jose L. Raygada2, Kabir Mendiratta1, Susan M. Seo2 and Glenn W. Kaatz1,2

1 John D. Dingell Department of Veterans Affairs Medical Center, Detroit, MI 48201, USA
2 Department of Medicine, Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, MI 48201, USA
3 École Supérieure de Microbiologie et Sécurité Alimentaire de Brest, Université de Bretagne Occidentale, Technopôle Brest-Iroise, 29280 Plouzané, France

Biocides and dyes are commonly employed in hospital and laboratory settings. Many of these agents are substrates for multiple-drugresistance (MDR)-conferring efflux pumps of both Gram-positive and Gram-negative organisms. Several such pumps have been identified inStaphylococcus aureus, and mutants overexpressing the NorA and MepA MDR pumps following exposure to fluoroquinolones have been identified. The effect of exposure to low concentrations of biocides and dyes on the expression of specific pump genes has not been evaluated. Using quantitative reverse-transcription PCR we found that exposure of clinical isolates to low concentrations of a variety of biocides and dyes in a single step, or to gradually increasing concentrations over several days, resulted in the appearance of mutants overexpressing mepA, mdeA, norA and norC, with mepA overexpression predominating. Overexpression was frequently associated with promoter-region or regulatory protein mutations. Mutants having significant increases in MICs of common pump substrates but no changes in expression of studied pump genes were also observed; in these cases changes in expression of as-yet-unidentified MDR pump genes may have occurred. Strains of S. aureus that exist in relatively protected environments and are repeatedly exposed to sublethal concentrations of biocides can develop efflux-related resistance to those agents, and acquisition of such strains poses a threat to patients treated with antimicrobial agents that are also substrates for those pumps, such as ciprofloxacin and moxifloxacin.