Cited by 317Bacterial biofilms and quorum sensingBacterial Genetics and BiotechnologyAntibiotic Resistance in Bacteria

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Community surveillance enhances Pseudomonas aeruginosa virulence during polymicrobial infection

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Korgaonkar, Aishwarya, Trivedi, Urvish, Rumbaugh, Kendra P., Whiteley, Marvin·2013·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1214550110PMC PMC3549110

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Abstract

Most infections result from colonization by more than one microbe. Within such polymicrobial infections, microbes often display synergistic interactions that result in increased disease severity. Although many clinical studies have documented the occurrence of synergy in polymicrobial infections, little is known about the underlying molecular mechanisms. A prominent pathogen in many polymicrobial infections is Pseudomonas aeruginosa, a Gram-negative bacterium that displays enhanced virulence during coculture with Gram-positive bacteria. In this study we discovered that during coinfection, P. aeruginosa uses peptidoglycan shed by Gram-positive bacteria as a cue to stimulate production of multiple extracellular factors that possess lytic activity against prokaryotic and eukaryotic cells. Consequently, P. aeruginosa displays enhanced virulence in a Drosophila model of infection when cocultured with Gram-positive bacteria. Inactivation of a gene (PA0601) required for peptidoglycan sensing mitigated this phenotype. Using Drosophila and murine models of infection, we also show that peptidoglycan sensing results in P. aeruginosa-mediated reduction in the Gram-positive flora in the infection site. Our data suggest that P. aeruginosa has evolved a mechanism to survey the microbial community and respond to Gram-positive produced peptidoglycan through production of antimicrobials and toxins that not only modify the composition of the community but also enhance host killing. Additionally, our results suggest that therapeutic strategies targeting Gram-positive bacteria might be a viable approach for reducing the severity of P. aeruginosa polymicrobial infections.

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Authors: Korgaonkar, A., Trivedi, U., Rumbaugh, K. P., & Whiteley, M.
Affiliations: The University of Texas at Austin (US)
Texas Tech University (US)
ORCID: Korgaonkar, Aishwarya
Trivedi, Urvish
Rumbaugh, Kendra P.
Whiteley, Marvin
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2012-12-31
Volume: 110
Issue: 3
Pages: 1059-1064
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1214550110
PMC: PMC3549110
OpenAlex: W2062817953
Cited by: 315
References: 59
Citations by year: 2026: 14 · 2025: 24 · 2024: 16 · 2023: 27 · 2022: 26 · 2021: 23 · 2020: 24 · 2019: 26 · 2018: 21 · 2017: 21 · 2016: 24 · 2015: 32 · 2014: 28 · 2013: 9
FWCI: 8.88
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Allergy and Infectious Diseases (R01AI075068)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
Keywords: Pseudomonas aeruginosa, co-infection, bacterial synergy, peptidoglycan sensing, Gram-positive bacteria, extracellular virulence factors, lytic activity, community-based surveillance
MeSH terms: Animals, Base Sequence, Disease Models, Animal, DNA, Bacterial, Drosophila melanogaster, Female, Genes, Bacterial, Humans, Male, Mutation, Peptidoglycan, Pseudomonas aeruginosa, Pseudomonas Infections, Staphylococcal Infections, Staphylococcus aureus, Virulence, Mice, Quorum Sensing, Coinfection

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Community surveillance enhances Pseudomonas aeruginosa virulence during polymicrobial infection

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