Bile Salt Hydrolase Degrades β-Lactam Antibiotics and Confers Antibiotic Resistance on Lactobacillus paragasseri

Kusada, Hiroyuki; Arita, Masanori; Tohno, Masanori; Tamaki, Hideyuki

doi:10.3389/fmicb.2022.858263

Cited by 29Probiotics and Fermented FoodsAntibiotic Resistance in BacteriaEnzyme Production and Characterization

Bile Salt Hydrolase Degrades β-Lactam Antibiotics and Confers Antibiotic Resistance on Lactobacillus paragasseri

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Kusada, Hiroyuki, Arita, Masanori, Tohno, Masanori, Tamaki, Hideyuki·2022·Frontiers in Microbiology

DOI 10.3389/fmicb.2022.858263PMC PMC9207391

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Abstract

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 Lactobacillus paragasseri JCM 5343 T 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 T 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.

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PVA may hydrolyze PenV, conferring resistance to this antibiotic.
“Although, PVA may also hydrolyze PenV, conferring resistance to this antibiotic [85].”
From Bile Salt Hydrolase Activity in the Food-Derived Strain Levilactobacillus brevis M3R3: Genomic and Functional Characterization (2026) · cites this paper as [85]
In Results and Discussion (page unavailable), the paper shows that LpBSH hydrolyzes penicillin G and proposes that it may mediate β-lactam resistance. It reports a susceptibility measurement for penicillin V, but does not show that PVA hydrolyzes penicillin V or thereby confers resistance to it. (LLM, conf=0.82)
Experimental — accuracy not yet measured
The role of BSH in deconjugation of bile salts is well established, whereas PVA appears to be involved in the degradation of penicillin-class antibiotics.
“The role of BSH in deconjugation of BSs is well established, whereas PVA appears to be involved in the degradation of penicillin-class antibiotics [85].”
From Bile Salt Hydrolase Activity in the Food-Derived Strain Levilactobacillus brevis M3R3: Genomic and Functional Characterization (2026) · cites this paper as [85]

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Self-citation

Authors: Kusada, H., Arita, M., Tohno, M., & Tamaki, H.
Affiliations: National Institute of Advanced Industrial Science and Technology (JP)
National Institute of Genetics (JP)
National Agriculture and Food Research Organization (JP)
University of Tsukuba (JP)
Corresponding author: Kusada, Hiroyuki
Tamaki, Hideyuki
ORCID: Kusada, Hiroyuki
Arita, Masanori
Tamaki, Hideyuki
Venue: Frontiers in Microbiology
Publisher: Frontiers Media SA
Published: 2022-06-06
Volume: 13
Pages: 858263-858263
ISSN: 1664-302X (ISSN-L)
DOI: 10.3389/fmicb.2022.858263
PMC: PMC9207391
OpenAlex: W4281672846
Cited by: 29
References: 58
Citations by year: 2026: 5 · 2025: 12 · 2024: 7 · 2023: 1 · 2022: 4
FWCI: 3.19
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Microbiology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: Ministry of Education, Culture, Sports, Science and Technology (JP19H05683, JP19H05679)
Japan Society for the Promotion of Science (JP19K16633)
Exploratory Research for Advanced Technology (JPMJER1502)
Japan Agency for Medical Research and Development (JP18gm6010019)
Topics: Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Enzyme Production and Characterization
Keywords: bile salt hydrolase, Lactobacillus paragasseri, beta-lactam antibiotics, penicillin degradation, antibiotic resistance, bifunctional enzyme, gut microbiota, lactic acid bacteria, penicillin acylase, multidrug resistance, phylogenetic diversity

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Bile Salt Hydrolase Degrades β-Lactam Antibiotics and Confers Antibiotic Resistance on Lactobacillus paragasseri

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