New insights into bacterial bile resistance mechanisms: the role of bile salt hydrolase and its impact on human health

Bustos, Ana Yanina; Valdez, Graciela Font de; Fadda, Silvina; Taranto, María Pía

doi:10.1016/j.foodres.2018.06.035

Cited by 118 publications

(78 citation statements)

References 152 publications

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“…1 The physiologic function of BSH is debated and the current three hypotheses are: (1) BSHs provide a nutritional advantage by liberating amino acids that can be used for carbon/nitrogen sources and energy generation via taurine as a terminal electron acceptor; (2) BSHs aid in incorporation of cholesterol and bile components into bacterial membranes; (3) BSHs provide a detoxification mechanism to diminish the inherent detergent properties of bile acids. 1,43 Bile salt hydrolases appear to enhance bacterial colonization within the lower gastrointestinal tract, but appears to be strain specific. 13 Some probiotic Lactobacillus strains have several BSH genes, thus highlighting the importance of deconjugation of bile acids for gut microbes.…”

Section: Diversification Of Host Bile Acids By Gut Microbesmentioning

confidence: 99%

“…1 In addition to membrane damage, bile acids impose a fitness challenge to gut microbes through disruption of macromolecule stability by interfering with RNA secondary structures, causing DNA damage and promoting protein misfolding (reviewed in Begley et al and more recently in Bustos et al). 1,43 Evidence of the direct antimicrobial effects of bile acids can be gleaned from murine models of biliary obstruction, which exhibit dramatic gut microbial community proliferation and increased bacterial translocation. 31,77 These effects can be ameliorated with administration of bile acids resulting in inhibition of bacterial overgrowth.…”

Section: Gut Microbial Influence On Composition Of the Host Bile Acidmentioning

confidence: 99%

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Diversification of host bile acids by members of the gut microbiota

2019

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Bile acid biotransformation is a collaborative effort by the host and the gut microbiome. Host hepatocytes synthesize primary bile acids from cholesterol. Once these host-derived primary bile acids enter the gastrointestinal tract, the gut microbiota chemically modify them into secondary bile acids. Interest into the gut-bile acid-host axis is expanding in diverse fields including gastroenterology, endocrinology, oncology, and infectious disease. This review aims to 1) describe the physiologic aspects of collaborative bile acid metabolism by the host and gut microbiota; 2) to evaluate how gut microbes influence bile acid pools, and in turn how bile acid pools modulate the gut microbial community structure; 3) to compare species differences in bile acid pools; and lastly, 4) discuss the effects of ursodeoxycholic acid (UDCA) administration, a common therapeutic bile acid, on the gut microbiota-bile acid-host axis.

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Section: Diversification Of Host Bile Acids By Gut Microbesmentioning

confidence: 99%

Section: Gut Microbial Influence On Composition Of the Host Bile Acidmentioning

confidence: 99%

Diversification of host bile acids by members of the gut microbiota

2019

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“…This included the bile salt hydrolase (BSH) choloylglycine hydrolase and putatively a tetronasin resistance-encoding permease gene. BSH is involved in the deconjugation (hydrolysis) of bile acids, which have antimicrobial activity, especially against Gram-positive bacteria (24). Therefore, acquisition of BSH could serve as a selective advantage for E. faecium for gut colonization.…”

Section: Figmentioning

confidence: 99%

Plasmids Shaped the Recent Emergence of the Major Nosocomial Pathogen Enterococcus faecium

Arredondo-Alonso

Top

McNally

et al. 2020

mBio

109

140

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Enterococcus faecium is a gut commensal of humans and animals but is also listed on the WHO global priority list of multidrug-resistant pathogens. Many of its antibiotic resistance traits reside on plasmids and have the potential to be disseminated by horizontal gene transfer. Here, we present the first comprehensive population-wide analysis of the pan-plasmidome of a clinically important bacterium, by whole-genome sequence analysis of 1,644 isolates from hospital, commensal, and animal sources of E. faecium. Long-read sequencing on a selection of isolates resulted in the completion of 305 plasmids that exhibited high levels of sequence modularity. We further investigated the entirety of all plasmids of each isolate (plasmidome) using a combination of short-read sequencing and machine-learning classifiers. Clustering of the plasmid sequences unraveled different E. faecium populations with a clear association with hospitalized patient isolates, suggesting different optimal configurations of plasmids in the hospital environment. The characterization of these populations allowed us to identify common mechanisms of plasmid stabilization such as toxin-antitoxin systems and genes exclusively present in particular plasmidome populations exemplified by copper resistance, phosphotransferase systems, or bacteriocin genes potentially involved in niche adaptation. Based on the distribution of k-mer distances between isolates, we concluded that plasmidomes rather than chromosomes are most informative for source specificity of E. faecium. IMPORTANCE Enterococcus faecium is one of the most frequent nosocomial pathogens of hospital-acquired infections. E. faecium has gained resistance against most commonly available antibiotics, most notably, against ampicillin, gentamicin, and vancomycin, which renders infections difficult to treat. Many antibiotic resistance traits, in particular, vancomycin resistance, can be encoded in autonomous and extrachromosomal elements called plasmids. These sequences can be disseminated to other isolates by horizontal gene transfer and confer novel mechanisms to source specificity. In our study, we elucidated the total plasmid content, referred to as the plasmidome, of 1,644 E. faecium isolates by using short- and long-read whole-genome technologies with the combination of a machine-learning classifier. This was fundamental to investigate the full collection of plasmid sequences present in our collection (pan-plasmidome) and to observe the potential transfer of plasmid sequences between E. faecium hosts. We observed that E. faecium isolates from hospitalized patients carried a larger number of plasmid sequences compared to that from other sources, and they elucidated different configurations of plasmidome populations in the hospital environment. We assessed the contribution of different genomic components and observed that plasmid sequences have the highest contribution to source specificity. Our study suggests that E. faecium plasmids are regulated by complex ecological constraints rather than physical interaction between hosts.

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“…The major BAs, cholate (primary BA) and deoxycholate and lithocholate (secondary BAs), were found to be in high and low levels in both the subtypes of IBD subjects than that of healthy controls (Mann-Whitney-Wilcoxon test, p < 0.05). The conjugated forms of primary BAs such as glycocholate, taurocholate, and taurochenodeoxycholate were found to be in high levels than healthy controls (Mann-Whitney-Wilcoxon test, p < 0.05), which suggests the lower abundance of genes encoding bile salt hydrolase [32,33].…”

Section: Comparative Fecal Metabolomics Analysis Of Bile Acids Betweementioning

confidence: 94%

Metagenomic analysis of bile salt biotransformation in the human gut microbiome

Das

Marcišauskas

et al. 2019

Preprint

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Background: In the biochemical milieu of human colon, bile acids act as signaling mediators between the host and its gut microbiota. Biotransformation of primary to secondary bile acids have been known to be involved in the immune regulation of human physiology. Several 16S amplicon-based studies with inflammatory bowel disease (IBD) subjects were found to have an association with the level of fecal bile acids. However, a detailed investigation of all the bile acid biotransformation genes involved in the secondary bile acid metabolism has not been performed. Results: Here, we report a comprehensive analysis of the bile acid biotransformation genes and their distribution at the phyla level. Based on the analysis of shotgun metagenomes, we found that the IBD subjects harbored a significantly lower abundance of these genes compared to the healthy controls. Majority of these genes originated from Firmicutes in comparison to other phyla. From metabolomics data, we found that the IBD subjects were measured with a significantly low level of secondary bile acids and high levels of primary bile acids compared to that of the healthy controls. Conclusions: Our bioinformatics-driven approach of identifying bile acid biotransformation genes predicts the bile salt biotransformation potential in the gut microbiota of IBD subjects. The functional level of dysbiosis likely contributes to the variation in the bile acid pool. This study sets the stage to envisage potential solutions to modulate the gut microbiome with the objective to restore the bile acid pool in the gut.

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New insights into bacterial bile resistance mechanisms: the role of bile salt hydrolase and its impact on human health

Cited by 118 publications

References 152 publications

Diversification of host bile acids by members of the gut microbiota

Diversification of host bile acids by members of the gut microbiota

Plasmids Shaped the Recent Emergence of the Major Nosocomial Pathogen Enterococcus faecium

Metagenomic analysis of bile salt biotransformation in the human gut microbiome

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