Cited by 188Antifungal resistance and susceptibilityBacterial biofilms and quorum sensingFungal and yeast genetics research

Enterococcus faecalis inhibits hyphal morphogenesis and virulence of Candida albicans

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Cruz, Melissa R., Graham, Carrie E., Gagliano, Bryce C., Lorenz, Michael C., Garsin, Danielle A.·2013·Infection and Immunity

Abstract

The Gram-positive bacterium Enterococcus faecalis and the fungus Candida albicans are both found as commensals in many of the same niches of the human body, such as the oral cavity and gastrointestinal (GI) tract. However, both are opportunistic pathogens and have frequently been found to be coconstituents of polymicrobial infections. Despite these features in common, there has been little investigation into whether these microbes affect one another in a biologically significant manner. Using a Caenorhabditis elegans model of polymicrobial infection, we discovered that E. faecalis and C. albicans negatively impact each other's virulence. Much of the negative effect of E. faecalis on C. albicans was due to the inhibition of C. albicans hyphal morphogenesis, a developmental program crucial to C. albicans pathogenicity. We discovered that the inhibition was partially dependent on the Fsr quorum-sensing system, a major regulator of virulence in E. faecalis . Specifically, two proteases regulated by Fsr, GelE and SerE, were partially required. Further characterization of the inhibitory signal revealed that it is secreted into the supernatant, is heat resistant, and is between 3 and 10 kDa. The substance was also shown to inhibit C. albicans filamentation in the context of an in vitro biofilm. Finally, a screen of an E. faecalis transposon mutant library identified other genes required for suppression of C. albicans hyphal formation. Overall, we demonstrate a biologically relevant interaction between two clinically important microbes that could affect treatment strategies as well as impact our understanding of interkingdom signaling and sensing in the human-associated microbiome.

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  • Enterococcus faecalis can inhibit C. albicans morphogenesis, biofilm formation, and overall virulence.

    “This is exemplified by a series of articles in the last few years by the Lorenz and Garsin groups, who initially reported on the interactions between Enterococcus faecalis and C. albicans, whereby the bacterium can inhibit C. albicans morphogenesis, biofilm formation, and overall virulence [59].”
  • Candida albicans interacts with several bacterial species found in the gut, such as Enterococcus and Escherichia species; those found in the vagina, such as Lactobacillus species; and those found in the lungs of patients with cystic fibrosis, such as Pseudomonas aeruginosa.

    “C. albicans also interacts with several bacterial species found in the gut, such as Enterococcus and Escherichia species; those found in the vagina, such as Lactobacillus species; and those found in the lungs of patients with cystic fibrosis, such as Pseudomonas aeruginosa (13, 34, 54, 78).”

    From <i>Candida albicans</i> Biofilms and Human Disease (2015) · cites this paper as [34]

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  1. [34]34. Garsin DA, Urbach J, Huguet-Tapia JC, Peters JE, Ausubel FM. 2004. Construction of an Enterococcus faecalis Tn917-mediated-gene-disruption library offers insight into Tn917 insertion patterns. J. Bacteriol. 186:7280–7289 [DOI] [PMC free article] [PubMed] [Google Scholar]

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Authors
Cruz, M. R., Graham, C. E., Gagliano, B. C., Lorenz, M. C., & Garsin, D. A.
Affiliations
The University of Texas Health Science Center at Houston (US)
Venue
Infection and Immunity
Published
2013-01
Volume
81
Issue
1
Pages
189-200
ISSN
  • 0019-9567 (ISSN-L)
  • 1098-5522
OpenAlex
W2165496886
Cited by
188
References
65
Citations by year
2026: 12 · 2025: 14 · 2024: 8 · 2023: 10 · 2022: 14 · 2021: 26 · 2020: 16 · 2019: 19 · 2018: 16 · 2017: 11 · 2016: 12 · 2015: 14 · 2014: 9 · 2013: 7
FWCI
6.63
Type
journal article
Language
en
Open access
Locations
  • Infection and Immunity (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Texas Health Science Center at Houston
  • National Institute of Allergy and Infectious Diseases (R01AI075091, R01AI076406, R56AI093699)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
Enterococcus faecalis, Candida albicans, hyphal morphogenesis, fungal virulence, co-infection, interkingdom signaling, Caenorhabditis elegans model, biofilm, transposon mutant screen, opportunistic pathogens, human microbiome
MeSH terms
Animals, Bacterial Proteins, Candida albicans, Candidiasis, Morphogenesis, Enterococcus faecalis, Virulence, Gram-Positive Bacterial Infections, Caenorhabditis elegans, Biofilms, Hyphae, Quorum Sensing, Coinfection

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