---
title: "ABC and MFS efflux transporters drive bile salt tolerance and low-level antibiotic resistance in E"
id: "pubmed-42742212"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42742212"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42742212/"
doi: "10.1128/msphere.00489-26"
published_at: "2026-09-15T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# ABC and MFS efflux transporters drive bile salt tolerance and low-level antibiotic resistance in E
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42742212
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42742212/)
- **DOI:** [10.1128/msphere.00489-26](https://doi.org/10.1128%2Fmsphere.00489-26)
- **Published At:** 2026-09-15T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Bacteria in the gastrointestinal tract must adapt to antimicrobial **bile salts** (BSs); the study investigated five putative transporters in **Enterococcus faecalis** for roles in BS adaptation and antibiotic resistance. - Exposure to 0.02% and 0.1% BS increased transcript levels of ef2593 and ef0575 by over fivefold; ef0420 increased ~12-fold; ef2592 and ef1814 showed no expression change under those conditions. - Overexpression of efflux pumps (EF2592, EF2593, EF0575, EF0420) in wild-type MMH594 increased colony-forming units (CFU/mL) after challenge with 0.3% BS, indicating enhanced tolerance; pre-exposure to 0.02% BS with EF2593 or EF0420 also conferred increased survival. - Multiple transporters contribute to the BS response in **E. faecalis**, suggesting redundancy or cooperative roles in adapting to higher BS concentrations. - In minimum inhibitory concentration (MIC) assays, specific overexpressors increased antibiotic resistance twofold: EF2592 and EF2593 for **daptomycin** and **vancomycin**; EF0420 for daptomycin and **oritavancin**; EF1814 for daptomycin, **levofloxacin**, oritavancin, and vancomycin. - Although EF0575 overexpression did not change antibiotic susceptibility, an EF0575 mutant showed increased susceptibility to daptomycin, linezolid, levofloxacin, and oritavancin, indicating a role in intrinsic tolerance. - Heterologous expression in **Lactococcus lactis** with nisin induction increased MICs for several antibiotics; EF1814 produced the largest effect with 4- to 16-fold MIC increases for daptomycin, levofloxacin, linezolid, and vancomycin. - Findings link host-associated environmental stress (bile salts) with acquisition or expression of low-level multidrug resistance, implying that transport systems selected for gut survival may raise antibiotic tolerance. - The identified **ABC** and **MFS** transporters represent potential targets to limit intestinal colonization by **E. faecalis** and to mitigate low-level antibiotic resistance. - Full experimental details (e.g., exact methods, strain constructions, statistical analyses) were not reported in the abstract and are found in the full article.
## Clinical Analysis & Structured Key Points
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Online ahead of print. # ABC and MFS efflux transporters mediate antibiotic resistance and bile salt tolerance in _Enterococcus faecalis_ [Q C Truong-Bolduc](https://pubmed.ncbi.nlm.nih.gov/?term=Truong-Bolduc+QC&cauthor_id=42742212)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#full-view-affiliation-1 "Infectious Diseases Division and Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA."), [Y Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+Y&cauthor_id=42742212)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#full-view-affiliation-1 "Infectious Diseases Division and Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA."), [S S Mello](https://pubmed.ncbi.nlm.nih.gov/?term=Mello+SS&cauthor_id=42742212)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#full-view-affiliation-2 "Department of Ophthalmology, Mass Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#full-view-affiliation-3 "Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA."), [M C Phillips](https://pubmed.ncbi.nlm.nih.gov/?term=Phillips+MC&cauthor_id=42742212)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#full-view-affiliation-1 "Infectious Diseases Division and Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA."), [M S Gilmore](https://pubmed.ncbi.nlm.nih.gov/?term=Gilmore+MS&cauthor_id=42742212)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#full-view-affiliation-2 "Department of Ophthalmology, Mass Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#full-view-affiliation-3 "Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA."), [D C Hooper](https://pubmed.ncbi.nlm.nih.gov/?term=Hooper+DC&cauthor_id=42742212)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#full-view-affiliation-1 "Infectious Diseases Division and Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.") Affiliations Expand ### Affiliations * 1 Infectious Diseases Division and Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. * 2 Department of Ophthalmology, Mass Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. * 3 Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA. * PMID: **42742212** * DOI: [ 10.1128/msphere.00489-26 ](https://doi.org/10.1128/msphere.00489-26) Item in Clipboard # ABC and MFS efflux transporters mediate antibiotic resistance and bile salt tolerance in _Enterococcus faecalis_ Q C Truong-Bolduc et al. mSphere. 2026. Show details Display options Display options Format Abstract PubMed PMID mSphere Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22mSphere%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22mSphere%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42742212/) . 2026 Sep 15:e0048926. doi: 10.1128/msphere.00489-26. Online ahead of print. ### Authors [Q C Truong-Bolduc](https://pubmed.ncbi.nlm.nih.gov/?term=Truong-Bolduc+QC&cauthor_id=42742212)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#short-view-affiliation-1 "Infectious Diseases Division and Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA."), [Y Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+Y&cauthor_id=42742212)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#short-view-affiliation-1 "Infectious Diseases Division and Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA."), [S S Mello](https://pubmed.ncbi.nlm.nih.gov/?term=Mello+SS&cauthor_id=42742212)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#short-view-affiliation-2 "Department of Ophthalmology, Mass Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#short-view-affiliation-3 "Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA."), [M C Phillips](https://pubmed.ncbi.nlm.nih.gov/?term=Phillips+MC&cauthor_id=42742212)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#short-view-affiliation-1 "Infectious Diseases Division and Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA."), [M S Gilmore](https://pubmed.ncbi.nlm.nih.gov/?term=Gilmore+MS&cauthor_id=42742212)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#short-view-affiliation-2 "Department of Ophthalmology, Mass Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#short-view-affiliation-3 "Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA."), [D C Hooper](https://pubmed.ncbi.nlm.nih.gov/?term=Hooper+DC&cauthor_id=42742212)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42742212/#short-view-affiliation-1 "Infectious Diseases Division and Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.") ### Affiliations * 1 Infectious Diseases Division and Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. * 2 Department of Ophthalmology, Mass Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. * 3 Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA. * PMID: **42742212** * DOI: [ 10.1128/msphere.00489-26 ](https://doi.org/10.1128/msphere.00489-26) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Bacteria that reside in the gastrointestinal tract must adapt to the antibacterial properties of bile salts (BSs) and other compounds. We investigated five putative transporters of the enteric-colonizing _Enterococcus faecalis_ for their roles in adaptation to BS and antibiotic resistance. Transcript levels of _ef2593_ and _ef0575_ increased over fivefold, and _ef0420_ increased 12-fold when exposed to 0.02% and 0.1% BS concentrations. No change in the expression of _ef2592_ or e _f1814_ was seen. _E. faecalis_ wild-type MMH594 overexpressing efflux pumps by plasmid constructs (EF2592, EF2593, EF0575, EF0420) or by a pre-exposure to 0.02% BS (EF2593 or EF0420) showed a higher CFU/mL than wild type alone when exposed to 0.3% BS, indicating adaptation of _E. faecalis_ to resist a higher BS level in the medium, and that _E. faecalis_ BS response involved multiple transporters. In MIC assays, the following overexpressors also showed a twofold increase in antibiotic resistance: EF2592 and EF2593 (daptomycin, vancomycin); EF0420 (daptomycin, oritavancin); and EF1814 (daptomycin, levofloxacin, oritavancin, and vancomycin). While no change in EF0575-overexpressor, mutant _0575_ showed a significant increase in susceptibility to daptomycin, linezolid, levofloxacin, and oritavancin. In addition, nisin-induced overexpression of several transporters from a plasmid in _Lactococcus lactis_ also increased the MICs of multiple antibiotics, most notably for EF1814, with a 4- to 16-fold increase in the MICs of daptomycin, levofloxacin, linezolid, and vancomycin. These data indicate that expression of multiple _E. faecalis_ transporters responds to bile salts and may contribute to survival and colonization in the gut, as well as causing low-level multidrug resistance.Bile salts are key antimicrobial components of the gastrointestinal tract, and bacterial adaptation to bile salt stress is critical for host colonization and persistence. In this study, we demonstrate that multiple _E. faecalis_ transporters are induced by bile salts and contribute to adaptation at physiologically relevant bile salt concentrations. Importantly, several of these transporters also confer low-level resistance to clinically important antibiotics, including daptomycin, vancomycin, levofloxacin, linezolid, and oritavancin. These findings suggest that transport systems selected for survival in the intestinal environment may have the unintended consequence of increasing antibiotic tolerance and multidrug resistance. By linking host-associated environmental stress with antimicrobial resistance phenotypes, this work advances our understanding of how gut colonization factors can influence bacterial persistence and therapeutic outcomes. The identified transporters represent potential targets for strategies to limit both intestinal colonization and antibiotic resistance in _E. faecalis_. **Keywords:** ABC transporter; E. faecalis; MFS efflux pump; MFS efflux pump.; antibiotics; bile salts. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ High-Level Antibiotic Tolerance of a Clinically Isolated Enterococcus faecalis Strain. ](https://pubmed.ncbi.nlm.nih.gov/33097497/) Gu H, Roy S, Zheng X, Gao T, Ma H, Soultan Z, Fortner C, Nangia S, Ren D.Gu H, et al.Appl Environ Microbiol. 2020 Dec 17;87(1):e02083-20. doi: 10.1128/AEM.02083-20. Print 2020 Dec 17.Appl Environ Microbiol. 2020.PMID: 33097497Free PMC article. * [ Sentinel Surveillance reveals phylogenetic diversity and detection of linear plasmids harboring _vanA_ and _optrA_ among enterococci collected in the United States. ](https://pubmed.ncbi.nlm.nih.gov/39404260/) Kent AG, Spicer LM, Campbell D, Breaker E, McAllister GA, Ewing TO, Longo C, Balbuena R, Burroughs M, Burgin A, Padilla J, Johnson JK, Halpin AL, McKay SL, Rasheed JK, Elkins CA, Karlsson M, Lutgring JD, Gargis AS.Kent AG, et al.Antimicrob Agents Chemother. 2024 Nov 6;68(11):e0059124. doi: 10.1128/aac.00591-24. Epub 2024 Oct 15.Antimicrob Agents Chemother. 2024.PMID: 39404260Free PMC article. * [ Phenotypic and molecular antibiotic resistance profile of Enterococcus faecalis and Enterococcus faecium isolated from different traditional fermented foods. ](https://pubmed.ncbi.nlm.nih.gov/23259502/) Sánchez Valenzuela A, Lavilla Lerma L, Benomar N, Gálvez A, Pérez Pulido R, Abriouel H.Sánchez Valenzuela A, et al.Foodborne Pathog Dis. 2013 Feb;10(2):143-9. doi: 10.1089/fpd.2012.1279. Epub 2012 Dec 21.Foodborne Pathog Dis. 2013.PMID: 23259502 * [ Treatment options for vancomycin-resistant enterococcal infections. ](https://pubmed.ncbi.nlm.nih.gov/11827558/) Linden PK.Linden PK.Drugs. 2002;62(3):425-41. doi: 10.2165/00003495-200262030-00002.Drugs. 2002.PMID: 11827558Review. * [ The Global Prevalence of Daptomycin, Tigecycline, and Linezolid-Resistant _Enterococcus faecalis_ and _Enterococcus faecium_ Strains From Human Clinical Samples: A Systematic Review and Meta-Analysis. ](https://pubmed.ncbi.nlm.nih.gov/34568377/) Dadashi M, Sharifian P, Bostanshirin N, Hajikhani B, Bostanghadiri N, Khosravi-Dehaghi N, van Belkum A, Darban-Sarokhalil D.Dadashi M, et al.Front Med (Lausanne). 2021 Sep 10;8:720647. doi: 10.3389/fmed.2021.720647. eCollection 2021.Front Med (Lausanne). 2021.PMID: 34568377Free PMC article. 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