biostudies-literatureLee WHA*STAR National Science ScholarshipNIEHS NIH HHSNational Institutes of HealthNIH HHSNIGMS NIH HHSe0057625https://www.ebi.ac.uk/biostudies/studies/S-EPMC12455946biostudies-literatureUnknown10(9)Pseudomonas aeruginosa and Staphylococcus aureus cause debilitating polymicrobial infections in diverse patient populations. Studies of these bacterial pathogens in coculture have shown that environmental variables, including Fe availability and the host-defense protein calprotectin (CP), impact coculture dynamics. To decipher how CP modulates interactions between P. aeruginosa and S. aureus, we employed dual-species RNA-seq to examine the transcriptional responses of both pathogens in coculture to CP treatment and metal depletion. Analysis of these responses revealed that, for both P. aeruginosa and S. aureus, CP treatment not only induced gene expression changes consistent with single- and multi-metal starvation responses but also induced gene exmSystemsCalprotectin protects Staphylococcus aureus in coculture with Pseudomonas aeruginosa by attenuating quorum sensing and decreasing the production of pseudomonal antimicrobials.PMC12455946P30 ES002109R01 GM126376Nolan EMLee WHOglesby AGfalseCalprotectin protects Staphylococcus aureus in coculture with Pseudomonas aeruginosa by attenuating quorum sensing and decreasing the production of pseudomonal antimicrobials.Pseudomonas aeruginosa and Staphylococcus aureus cause debilitating polymicrobial infections in diverse patient populations. Studies of these bacterial pathogens in coculture have shown that environmental variables, including Fe availability and the host-defense protein calprotectin (CP), impact coculture dynamics. To decipher how CP modulates interactions between P. aeruginosa and S. aureus, we employed dual-species RNA-seq to examine the transcriptional responses of both pathogens in coculture to CP treatment and metal depletion. Analysis of these responses revealed that, for both P. aeruginosa and S. aureus, CP treatment not only induced gene expression changes consistent with single- and multi-metal starvation responses but also induced gene ex2025-01-01T00:00:00Z2025 Sep2026-06-04T02:00:04.222Z2026-05-31T03:06:37.513ZS-EPMC124559464090569810.1128/msystems.00576-25