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大环内酯类抗生素耐药性及乳酸菌分离株对抗生素的体外耐药选择。

Macrolide resistance and in vitro selection of resistance to antibiotics in Lactobacillus isolates.

机构信息

Lab of Clinical-Chemistry and Microbiology, IRCCS Galeazzi Institute, Via R. Galeazzi 4, 20161 Milan, Italy.

出版信息

J Microbiol. 2011 Aug;49(4):651-6. doi: 10.1007/s12275-011-0470-1. Epub 2011 Sep 2.

Abstract

Spreading of resistance to antibiotics is of great concern due to the increasing rate of isolation of multiresistant pathogens. Since commensal bacteria may transfer determinants of resistance to pathogens, studies on development of resistance should include also lactobacilli. Resistance to macrolides, penicillins and tetracycline was determined in 40 isolates of Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus crispatus, and Lactobacillus casei isolated from faeces of apparently healthy volunteers. Frequency of mutation and changes in susceptibility after serial exposure to these antibiotics at concentrations of 4× and 8× MIC were evaluated in susceptible isolates. Acquired resistance was defined as an increment in MIC values of at least four times in respect to the pre-selection values. Resistance to macrolides and/or tetracycline was identified in 14 and 4 isolates, respectively. ermB gene and A2058G mutation in 23S rRNA were detected in macrolide resistant isolates. Frequencies of mutation of susceptible isolates (n=26) were lower for ampicillin and erythromycin than for tetracycline. Serial exposure to antibiotics led to selection of resistant mutants. However, acquired resistance was rather unstable and was lost after subcultures in antibiotic-free medium in most mutants. Resistance to erythromycin was associated to a A2058G mutation in 23S rRNA. In conclusion, results indicate that resistance to macrolides and tetracycline is present among intestinal lactobacilli. Decrease in susceptibility following serial exposure to antibiotics might occur in lactobacilli, in a strain- and antibiotic-dependent way. Since lactobacilli are often used as probiotics, their ability to acquire resistance should be evaluated for isolates candidate to be included in probiotics based products.

摘要

抗生素耐药性的传播令人担忧,因为多耐药病原体的分离率不断增加。由于共生菌可能将耐药性决定因素转移给病原体,因此对耐药性发展的研究还应包括乳杆菌。从看似健康的志愿者的粪便中分离出 40 株嗜酸乳杆菌、植物乳杆菌、卷曲乳杆菌和干酪乳杆菌,测定其对大环内酯类、青霉素类和四环素类的耐药性。在易感性分离物中,评估了在 4×和 8×MIC 浓度下连续暴露于这些抗生素时突变频率和药敏性变化。获得性耐药定义为 MIC 值至少增加 4 倍,与预选择值相比。分别在 14 和 4 株分离物中鉴定出对大环内酯类和/或四环素类的耐药性。在大环内酯类耐药分离物中检测到 ermB 基因和 23S rRNA 的 A2058G 突变。易感性分离物(n=26)对氨苄西林和红霉素的突变频率低于四环素。抗生素的连续暴露导致耐药突变体的选择。然而,获得性耐药性相当不稳定,在大多数突变体中,在用无抗生素培养基传代后,耐药性就会丢失。对红霉素的耐药性与 23S rRNA 的 A2058G 突变有关。总之,结果表明,肠道乳杆菌存在对大环内酯类和四环素类的耐药性。在抗生素连续暴露后,敏感性下降可能会以菌株和抗生素依赖的方式发生在乳杆菌中。由于乳杆菌常被用作益生菌,因此应评估候选益生菌分离物获得耐药性的能力。

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