Lactobacillus rhamnosus is an important lactic acid bacterium that is predominantly used as a probiotic supplement. This bacterium secretes immunomodulatory and antibacterial peptides that are necessary for the probiotic trait. This organism also occupies diverse ecological niches, such as gastrointestinal tracts and the oral cavity. Several studies have shown that L. rhamnosus is prone to spontaneous genome rearrangement irrespective of the ecological origins. We previously characterized an oral isolate of L. rhamnosus, LRB, which is genetically closely related to the widely used probiotic strain L. rhamnosus LGG. In this study, we isolated a nontargeted mutant that was particularly sensitive to acid stress. Using next generation sequencing, we further mapped the putative mutations in the genome and found that the mutant had acquired a deletion of 75 base pairs in the rplD gene that encodes the large ribosomal subunit L4. The mutant had a growth defect at 37°C and at ambient temperature. Further antibiotic sensitivity analyses indicated that the mutant is relatively more resistant to erythromycin and chloramphenicol; two antibiotics that target the 50S subunit. In contrast, the mutant was more sensitive to tetracycline, which targets the 30S subunit. Thus, it appears that nontargeted mutations could significantly alter the antibiotic resistance profile of L. rhamnosus. Our study raises concern that probiotic use of L. rhamnosus should be carefully monitored to avoid unintended consequences.

中文翻译：

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鼠李糖乳杆菌LRB的核糖体蛋白L4改变了对大环内酯类和其他抗生素的耐药性。

鼠李糖乳杆菌是一种重要的乳酸菌，主要用作益生菌补充剂。该细菌分泌益生菌性状所必需的免疫调节和抗菌肽。这种生物还占据着各种生态位，例如胃肠道和口腔。数项研究表明，鼠李糖乳杆菌不论其生态起源如何，均易于自发进行基因组重排。我们以前表征了鼠李糖乳杆菌，LRB的口腔分离株，这与广泛使用的益生菌菌株鼠李糖乳杆菌在遗传上密切相关LGG。在这项研究中，我们分离了对酸胁迫特别敏感的非靶向突变体。使用下一代测序，我们进一步在基因组中定位推定的突变，发现该突变体在编码大核糖体亚基L4的rplD基因中获得了75个碱基对的缺失。突变体在37°C和环境温度下有生长缺陷。进一步的抗生素敏感性分析表明，该突变体对红霉素和氯霉素的抗性相对较高。靶向50S亚基的两种抗生素。相反，该突变体对靶向30S亚基的四环素更敏感。因此，似乎非靶向突变可显着改变鼠李糖乳杆菌的抗药性。我们的研究引起关注，对鼠李糖乳杆菌益生菌的使用应仔细监控，以免发生意料之外的后果。