Kusada Hiroyuki, Arita Masanori, Tohno Masanori, Tamaki Hideyuki
Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
Bioinformation and DDBJ Center, National Institute of Genetics, Mishima, Japan.
Front Microbiol. 2022 Jun 6;13:858263. doi: 10.3389/fmicb.2022.858263. eCollection 2022.
Bile salt hydrolase (BSH) is a well-characterized probiotic enzyme associated with bile detoxification and colonization of lactic acid bacteria in the human gastrointestinal tract. Here, we isolated a putative BSH (LpBSH) from the probiotic bacterium JCM 5343 and demonstrated its bifunctional activity that allows it to degrade not only bile salts but also the antibiotic (penicillin). Although antibiotic resistance and bile detoxification have been separately recognized as different microbial functions, our findings suggest that bifunctional BSHs simultaneously confer ecological advantages to host gut bacteria to improve their survival in the mammalian intestine by attaining a high resistance to bile salts and β-lactams. Strain JCM 5343 showed resistance to both bile salts and β-lactam antibiotics, suggesting that LpBSH may be involved in this multi-resistance of the strain. We further verified that such bifunctional enzymes were broadly distributed among the phylogeny, suggesting that the bifunctionality may be conserved in other BSHs of gut bacteria. This study revealed the physiological role and phylogenetic diversity of bifunctional enzymes degrading bile salts and β-lactams in gut bacteria. Furthermore, our findings suggest that the hitherto-overlooked penicillin-degrading activity of penicillin acylase could be a potential new target for the probiotic function of gut bacteria.
胆汁盐水解酶（BSH）是一种已被充分表征的益生菌酶，与人类胃肠道中乳酸菌的胆汁解毒和定殖有关。在此，我们从益生菌细菌JCM 5343中分离出一种假定的BSH（LpBSH），并证明了其双功能活性，即它不仅能够降解胆汁盐，还能降解抗生素（青霉素）。尽管抗生素抗性和胆汁解毒已被分别视为不同的微生物功能，但我们的研究结果表明，双功能BSH通过对胆汁盐和β-内酰胺类药物具有高抗性，同时赋予宿主肠道细菌生态优势，以提高它们在哺乳动物肠道中的存活率。菌株JCM 5343对胆汁盐和β-内酰胺类抗生素均表现出抗性，这表明LpBSH可能参与了该菌株的这种多重抗性。我们进一步证实，这种双功能酶在系统发育中广泛分布，这表明双功能特性可能在肠道细菌的其他BSH中保守存在。本研究揭示了肠道细菌中降解胆汁盐和β-内酰胺类药物的双功能酶的生理作用和系统发育多样性。此外，我们的研究结果表明，青霉素酰化酶迄今被忽视的青霉素降解活性可能是肠道细菌益生菌功能的一个潜在新靶点。
