| Title: |
Loss of Bacteroides thetaiotaomicron bile acid-altering enzymes impacts bacterial fitness and the global metabolic transcriptome |
| Authors: |
McMillan, Arthur S.; Foley, Matthew H.; Perkins, Caroline E.; Theriot, Casey M. |
| Contributors: |
Theis, Kevin R.; NIGMS |
| Source: |
Microbiology Spectrum ; volume 12, issue 1 ; ISSN 2165-0497 |
| Publisher Information: |
American Society for Microbiology |
| Publication Year: |
2024 |
| Description: |
Bacteroides thetaiotaomicron ( B. theta ) is a Gram-negative gut bacterium that encodes enzymes that alter the bile acid pool in the gut. Primary bile acids are synthesized by the host liver and are modified by gut bacteria. B. theta encodes two bile salt hydrolases, as well as a hydroxysteroid dehydrogenase. We hypothesize that B. theta modifies the bile acid pool in the gut to provide a fitness advantage for itself. To investigate each gene’s role, different combinations of genes encoding bile acid-altering enzymes ( bshA , bshB , and hsdhA ) were knocked out by allelic exchange, including a triple KO. Bacterial growth and membrane integrity assays were done in the presence and absence of bile acids. To explore if B. theta’s response to nutrient limitation changes due to the presence of bile acid-altering enzymes, RNA sequencing (RNASeq) analysis of wild type (WT) and triple knockout (KO) strains in the presence and absence of bile acids was done. WT B. theta is more sensitive to deconjugated bile acids such as cholate, chenodeoxycholate (CDCA), and deoxycholate (DCA) compared with the triple KO. These deconjugated bile acids also decreased membrane integrity of both WT and triple KO. The presence of bshB is detrimental to growth in conjugated forms of CDCA and DCA. RNASeq analysis also showed that bile acid exposure impacts multiple metabolic pathways in B. theta , but DCA significantly increases expression of many genes in carbohydrate metabolism, specifically those in polysaccharide utilization loci or PULs, in nutrient-limited conditions. This study suggests that bile acids B. theta encounters in the gut may signal the bacterium to increase or decrease its utilization of carbohydrates. Further study looking at the interactions between bacteria, bile acids, and the host may inform rationally designed probiotics and diets to ameliorate inflammation and disease. IMPORTANCE Recent work on bile salt hydrolases (BSHs) in Gram-negative bacteria, such as Bacteroides, has primarily focused on how they can ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1128/spectrum.03576-23 |
| Availability: |
https://doi.org/10.1128/spectrum.03576-23; https://journals.asm.org/doi/pdf/10.1128/spectrum.03576-23 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; https://journals.asm.org/non-commercial-tdm-license |
| Accession Number: |
edsbas.E1AD34AD |
| Database: |
BASE |