Bile Salts Differentially Enhance Resistance of Enterohemorrhagic Escherichia coli O157:H7 to Host Defense Peptides.
Gadishaw-Lue. Crystal C; Banaag. Alyssa A; Birstonas. Sarah S; Francis. Aju-Sue AS; Barnett Foster. Debora D
Key Findings
- Bile salts boost EHEC resistance to the defensins HD‑5 and HNP‑1 via the basRS two‑component system and the arnT lipid A modification pathway.
- Bile salts do NOT change EHEC resistance to the antimicrobial peptide LL‑37, even when the LL‑37‑cleaving protease OmpT is removed.
- In a Galleria mellonella infection model, bile‑treated wild‑type EHEC caused higher mortality than a basS mutant, indicating bile‑induced virulence depends on basS.
Practical Outcomes
- For DIY health enthusiasts considering LL‑37 supplementation, normal bile in the small intestine is unlikely to diminish its antibacterial action against EHEC. However, strategies that rely on boosting defensin (HD‑5, HNP‑1) activity may be less effective when bile salts are present. The findings are mainly of scientific interest and don’t suggest new dosing or protocol changes for most users.
Summary
The study shows that when the gut bacteria EHEC encounters normal bile salts, it becomes tougher against two natural gut antibiotics (HD-5 and HNP-1) but not against another one called LL‑37. This resistance depends on specific bacterial genes. In a wax‑moth infection model, bile‑treated normal bacteria were more deadly than a mutant lacking one of those genes.
Abstract
During passage through the human gastrointestinal tract, enterohemorrhagic <i>Escherichia coli</i> (EHEC) is exposed to membrane-damaging bile in the small intestine. We previously reported that EHEC treatment with a physiological bile salt mixture upregulates <i>basRS</i>, encoding a two-component system, and <i>arnBCADTEF</i>, encoding the aminoarabinose lipid A modification pathway (J. V. Kus, A. Gebremedhin, V. Dang, S. L. Tran, A. Serbanescu, and D. Barnett Foster, J Bacteriol 193: 4509-4515, 2011, https://doi.org/10.1128/JB.00200-11). The present study examined the effect of bile salt mix (BSM) treatment on EHEC resistance to three human gastrointestinal defense peptides-HD-5, HNP-1, and LL-37-as well as the role of <i>basRS</i> and <i>arnT</i> in the respective responses. After BSM treatment, EHEC resistance to HD-5 and HNP-1 was significantly increased in a BSM-, defensin dose-dependent manner. The resistance phenotype was dependent on both <i>basRS</i> and <i>arnT</i> However, the BSM treatment did not alter EHEC resistance to LL-37, even when the <i>ompT</i> gene, encoding an LL-37 cleavage protease, was disrupted. Interestingly, enteropathogenic <i>E. coli</i>, a related pathogen that infects the small intestine, showed a similar BSM-induced resistance phenotype. Using a model of EHEC infection in <i>Galleria mellonella</i>, we found significantly lower survival rates in wax moth larvae infected with BSM-treated wild-type EHEC than in those infected with a BSM-treated <i>basS</i> mutant, suggesting that treatment with a physiological BSM enhances virulence through a <i>basS</i>-mediated pathway. The results of this investigation provide persuasive evidence that bile salts typically encountered during transit through the small intestine can serve as an environmental cue for EHEC, enhancing resistance to several key host defense peptides.
Study Information
pubmed
2021
2021-01-19T00:00:00.000Z
10.1128/iai.00719-20