Disruptions in outer membrane-peptidoglycan interactions enhance bile salt resistance in O-antigen-producing E. coli

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dc.contributor.authorQin, J.
dc.contributor.authorHong, Y.
dc.contributor.authorVollmer, W.
dc.contributor.authorMorona, R.
dc.contributor.authorTotsika, M.
dc.contributor.editorGibbs, K.A.
dc.date.issued2025
dc.description.abstractBile salts (BS) are antimicrobials that disrupt bacterial cell membranes and induce oxidative stress. The gut bacterium Escherichia coli is naturally resistant to BS, including the model strain K12 MG1655 that produces a lipopolysaccharide (LPS) without O-antigen (OAg) on the cell surface. Paradoxically, we have previously shown that restoring a wild-type like LPS with attached OAg (MG1655-S) sensitizes E. coli K12 to exogenous BS. In this study, we investigate this phenomenon. We show that mutations causing truncation of the LPS core oligosaccharide render MG1655-S strains even more susceptible to BS compared to MG1655. These mutants phenocopy a K-12 MG1655-S ΔwaaL mutant, which is defective in OAg ligase, primarily due to periplasmic accumulation of the unligated lipid-linked UndPP-OAg. Through the characterization of BS-resistant suppressor mutants of MG1655-S ΔwaaL, we identify key genetic disruptions involved in resistance. Notably, we observed the highest BS resistance in strains with a weaker connection between the outer membrane (OM) and peptidoglycan (PG), including strains lacking the major OM-anchored, PG-binding proteins OmpA or Lpp. Expressing versions of OmpA and Lpp that lack PG-binding capacity also enhanced the BS resistance. Our data suggest that BS-induced stress in OAg-producing E. coli is due to the spatial constraints between OM and PG and that mutations disrupting OM–PG interactions alleviate this stress, thereby enhancing BS resistance. These findings provide new insights into a major challenge E. coli faces in the gut environment, where it needs to produce OAg for stable colonization and immune evasion while resisting the antimicrobial activity of BS.
dc.description.statementofresponsibilityJilong Qin, Yaoqin Hong, Waldemar Vollmer, Renato Morona, Makrina Totsika
dc.identifier.citationmBio, 2025; 16(10):e0218425-1-e0218425-20
dc.identifier.doi10.1128/mbio.02184-25
dc.identifier.issn2161-2129
dc.identifier.issn2150-7511
dc.identifier.orcidMorona, R. [0000-0001-7009-7440]
dc.identifier.urihttps://hdl.handle.net/2440/147893
dc.language.isoen
dc.publisherAmerican Society for Microbiology
dc.relation.granthttp://purl.org/au-research/grants/arc/DP210101317
dc.rightsCopyright © 2025 Qin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
dc.source.urihttps://doi.org/10.1128/mbio.02184-25
dc.subjectpolysaccharides; cell envelope; O antigen; peptidoglycan; Lpp; OmpA
dc.subject.meshEscherichia coli
dc.subject.meshEscherichia coli K12
dc.subject.meshBile Acids and Salts
dc.subject.meshPeptidoglycan
dc.subject.meshLipopolysaccharides
dc.subject.meshO Antigens
dc.subject.meshBacterial Outer Membrane Proteins
dc.subject.meshEscherichia coli Proteins
dc.subject.meshDrug Resistance, Bacterial
dc.subject.meshMutation
dc.subject.meshBacterial Outer Membrane
dc.titleDisruptions in outer membrane-peptidoglycan interactions enhance bile salt resistance in O-antigen-producing E. coli
dc.typeJournal article
pubs.publication-statusPublished online

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