PT - JOURNAL ARTICLE AU - Luke K. Brewer AU - Weiliang Huang AU - Maureen A. Kane AU - Amanda G. Oglesby-Sherrouse TI - Sessile growth reveals novel paradigms of <em>Pseudomonas aeruginosa</em> iron-regulated antimicrobial activity against <em>Staphylococcus aureus</em> AID - 10.1101/765115 DP - 2019 Jan 01 TA - bioRxiv PG - 765115 4099 - http://biorxiv.org/content/early/2019/09/11/765115.short 4100 - http://biorxiv.org/content/early/2019/09/11/765115.full AB - Pseudomonas aeruginosa and Staphylococcus aureus are opportunistic pathogens that cause chronic, polymicrobial infections. Each pathogen possesses a complex regulatory network that modulates iron acquisition and virulence. However, our current knowledge of these networks is largely based on studies with shaking cultures, which are not likely representative of microbial communities in vivo. Here, we provide proteomic, metabolic, and genetic evidence that iron regulation is altered in sessile P. aeruginosa cultures. We further demonstrate that iron-regulated interactions between P. aeruginosa and S. aureus are mediated by distinct factors in shaking versus sessile bacterial cultures. Moreover, we identified type 6 secretion as a target of iron regulation in P. aeruginosa in static but not shaking conditions, and co-culture studies suggest this system may contribute to antimicrobial activity against S. aureus in static conditions. These results yield new bacterial iron regulation paradigms and highlight the need for re-defining iron homeostasis in sessile microbial communities.