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Allelic variation of bile salt hydrolase genes in Lactobacillus salivarius does not determine bile resistance levels.
Fang, Fang Li, Yin Bumann, Mario Raftis, Emma J Casey, Pat G Cooney, Jakki C Walsh, Martin A O'Toole, Paul W
Fang, Fang
Li, Yin
Bumann, Mario
Raftis, Emma J
Casey, Pat G
Cooney, Jakki C
Walsh, Martin A
O'Toole, Paul W
Advisors
Editors
Other Contributors
Date
2009-09
Date Submitted
Keywords
Other Subjects
Subject Mesh
Alleles
Alleles
Amidohydrolases
Amidohydrolases
Animals
Animals
Bacterial Proteins
Bacterial Proteins
Bile Acids and Salts
Bile Acids and Salts
Drug Resistance, Bacterial
Drug Resistance, Bacterial
Genetic Variation
Genetic Variation
Humans
Humans
Intestines
Intestines
Lactobacillus
Lactobacillus
Mice
Mice
Microbial Sensitivity Tests
Microbial Sensitivity Tests
Molecular Sequence Data
Molecular Sequence Data
Mutation
Mutation
Oligonucleotide Array Sequence Analysis
Oligonucleotide Array Sequence Analysis
Phylogeny
Phylogeny
Alleles
Amidohydrolases
Amidohydrolases
Animals
Animals
Bacterial Proteins
Bacterial Proteins
Bile Acids and Salts
Bile Acids and Salts
Drug Resistance, Bacterial
Drug Resistance, Bacterial
Genetic Variation
Genetic Variation
Humans
Humans
Intestines
Intestines
Lactobacillus
Lactobacillus
Mice
Mice
Microbial Sensitivity Tests
Microbial Sensitivity Tests
Molecular Sequence Data
Molecular Sequence Data
Mutation
Mutation
Oligonucleotide Array Sequence Analysis
Oligonucleotide Array Sequence Analysis
Phylogeny
Phylogeny
Planned Date
Start Date
Collaborators
Principal Investigators
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19592587.pdf
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Alternative Titles
Publisher
Abstract
Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host.
Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host.
Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host.
Language
en
ISSN
1098-5530
eISSN
ISBN
DOI
10.1128/JB.00506-09
PMID
19592587