phenazines dictate site-specific competitive interactions with .

and are Gram-negative opportunistic pathogens that frequently colonize the human body and are major causes of infection. These bacteria are often co-isolated in polymicrobial urinary tract and lung infections, the latter of which is associated with increased disease severity and worse clinical outcomes. Despite their overlapping niches and clinical relevance, little is known about how these two pathogens interact and how those interactions influence human health. Given the growing recognition that microbial interactions are key drivers of disease, we investigated how and influence one another. We discovered an antagonistic interaction in which restricts the growth of . This inhibition is driven by phenazine production in , specifically the secondary metabolites pyocyanin and pyorubin, which are both necessary and sufficient to suppress growth. Using a diverse set of clinical isolates, we found that this antagonism is strain dependent. Both the susceptibility of to phenazines and the ability of to restrict growth varies between strains. Moreover, the necessity of phenazine production is specific to the site of infection. Together, these findings demonstrate that strain background and environmental context are critical determinants of pathogen interactions. Our work underscores the importance of considering these variables when investigating how microbial interactions influence infection and disease outcomes.