Due to their frequent coexistence in many polymicrobial infections, including in patients with burn or chronic wounds or cystic fibrosis, recent studies have started to investigate the mechanistic details of the interaction between the opportunistic pathogens and . rapidly outcompetes under co-cultivation conditions, which is mediated by several of 's virulence factors. Here, we report that polyphosphate (polyP), an efficient stress defense system and virulence factor in , plays a role for the pathogen's ability to inhibit and kill in a contact-independent manner. We show that cells characterized by low polyP.level are less detrimental to growth and survival while the gram-positive pathogen is significantly more compromised by the presence of cells that produce high level of polyP. We show that the polyP.dependent phenotype could be a direct effect by the biopolymer, as polyP.is present in the spent media and causes significant damage to the cell envelope. However, more likely is that polyP.apos;s effects are indirect through the regulation of one of virulence factors, pyocyanin. We show that pyocyanin production in occurs polyP.dependent and harms through membrane damage and the generation of reactive oxygen species, resulting in increased expression of antioxidant enzymes. In summary, our study adds a new component to the list of biomolecules that the gram-negative pathogen generates to compete with for resources.
