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Staphylococcal secreted cytotoxins are competition sensing signals for Pseudomonas aeruginosa

Wang, Grace Z. and Warren, Elizabeth A. and Haas, Allison L. and Sánchez Peña, Andrea and Kiedrowski, Megan R. and Lomenick, Brett and Chou, Tsui-Fen and Bomberger, Jennifer M. and Tirrell, David A. and Limoli, Dominique H. (2023) Staphylococcal secreted cytotoxins are competition sensing signals for Pseudomonas aeruginosa. . (Unpublished)

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Coinfection with two notorious opportunistic pathogens, the Gram-negative Pseudomonas aeruginosa and Gram-positiveStaphylococcus aureus, dominates chronic pulmonary infections. While coinfection is associated with poor patient outcomes, the interspecies interactions responsible for such decline remain unknown. Here, we dissected molecular mechanisms of interspecies sensing between P. aeruginosa and S. aureus. We discovered that P. aeruginosa senses S. aureus secreted peptides and, counterintuitively, moves towards these toxins. P. aeruginosa tolerates such a strategy through “competition sensing”, whereby it preempts imminent danger/competition by arming cells with type six secretion (T6S) and iron acquisition systems. Intriguingly, while T6S is predominantly described as weaponry targeting Gram-negative and eukaryotic cells, we find that T6S is essential for full P. aeruginosa competition with S. aureus, a previously undescribed role for T6S. Importantly, competition sensing was activated during coinfection of bronchial epithelia, including T6S islands targeting human cells. This study reveals critical insight into both interspecies competition and how antagonism may cause collateral damage to the host environment.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Wang, Grace Z.0000-0002-0938-304X
Haas, Allison L.0000-0002-2154-4328
Sánchez Peña, Andrea0000-0002-4843-3652
Kiedrowski, Megan R.0000-0003-4610-182X
Lomenick, Brett0000-0002-5023-9998
Chou, Tsui-Fen0000-0003-2410-2186
Bomberger, Jennifer M.0000-0003-4767-6238
Tirrell, David A.0000-0003-3175-4596
Limoli, Dominique H.0000-0002-4130-337X
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This work was supported by the Jacobs Institute for Molecular Engineering for Medicine and the Center for Environmental Microbial Interactions at Caltech, and by the Institute for Collaborative Biotechnologies through cooperative agreement W911NF-19-2-0026 from the U.S. Army Research Office, the Cystic Fibrosis Foundation (LIMOLI19R3 to DHL and BOMBER18G0 to JMB), and the National Institutes of Health (1R35GM142760-01 to DHL and 1R01HL142587 to JMB). We thank Drs. Megan Bergkessel (University of Dundee), Melanie Spero (University of Oregon), Alex Horswill (University of Colorado Denver), Mike Schurr (University of Colorado Denver), and Li Wu (University of Iowa) for helpful discussions and valuable insight. We also thank members of the Limoli and Tirrell Labs for careful editing of the manuscript and helpful discussions. We thank Dr. Jeff Jones (Caltech) for an in-house pipeline for proteomics data processing, Dr. J. Muse Davis for the use of the stereoscope, and Drs. Joseph Mougous and Anupama Khare for the generous gifts of the ClpV1-GFPmut3 and P’pvdA-mScarlet reporters, respectively. The authors have declared no competing interest.
Group:Jacobs Institute for Molecular Engineering for Medicine, Caltech Center for Environmental Microbial Interactions (CEMI)
Funding AgencyGrant Number
Jacobs Institute for Molecular Engineering for MedicineUNSPECIFIED
Caltech Center for Environmental Microbial Interactions (CEMI)UNSPECIFIED
Army Research Office (ARO)W911NF-19-2-0026
Cystic Fibrosis FoundationLIMOLI19R3
Cystic Fibrosis FoundationBOMBER18G0
Record Number:CaltechAUTHORS:20230316-182348000.27
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:120144
Deposited By: George Porter
Deposited On:21 Mar 2023 18:45
Last Modified:21 Mar 2023 18:45

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