{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:01:58Z","timestamp":1783000918316,"version":"3.54.5"},"posted":{"date-parts":[[2023,12,6]]},"group-title":"Microbiology","reference-count":102,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  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\n                  <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                  and\n                  <jats:italic>Staphylococcus aureus<\/jats:italic>\n                  .\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  rapidly outcompetes\n                  <jats:italic>S. aureus<\/jats:italic>\n                  under\n                  <jats:italic>in vitro<\/jats:italic>\n                  co-cultivation conditions, which is mediated by several of\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  \u2019s virulence factors. Here, we report that polyphosphate (polyP), an efficient stress defense system and virulence factor in\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  , plays a role for the pathogen\u2019s ability to inhibit and kill\n                  <jats:italic>S. aureus<\/jats:italic>\n                  in a contact-independent manner. We show that\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  cells characterized by low polyP level are less detrimental to\n                  <jats:italic>S. aureus<\/jats:italic>\n                  growth and survival while the gram-positive pathogen is significantly more compromised by the presence of\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  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\n                  <jats:italic>S. aureus<\/jats:italic>\n                  cell envelope. However, more likely is that polyP\u2019s effects are indirect through the regulation of one of\n                  <jats:italic>P. aeruginosa\u2019s<\/jats:italic>\n                  virulence factors, pyocyanin. We show that pyocyanin production in\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  occurs polyP-dependent and harms\n                  <jats:italic>S. aureus<\/jats:italic>\n                  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\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  generates to compete with\n                  <jats:italic>S. aureus<\/jats:italic>\n                  for resources.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>IMPORTANCE<\/jats:title>\n                  <jats:p>\n                    How do interactions between microorganisms shape the course of polymicrobial infections? Previous studies have provided evidence that the two opportunistic pathogens\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    and\n                    <jats:italic>S. aureus<\/jats:italic>\n                    generate molecules that modulate their interaction with potentially significant impact on disease outcomes. Our study identified the biopolymer polyP as a new effector molecule that impacts\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    \u2019s interaction with\n                    <jats:italic>S. aureus<\/jats:italic>\n                    . We show that\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    kills\n                    <jats:italic>S. aureus<\/jats:italic>\n                    in a polyP-dependent manner, which occurs primarily through the polyP-dependent production of the\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    virulence factor pyocyanin. Our findings add a new role for polyP to an already extensive list of functions. A more in-depth understanding of how polyP influences interspecies interactions is critical, as targeting polyP synthesis in bacteria such as\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    may have a significant impact on other microorganisms and potentially result in dynamic changes in the microbial composition.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.12.05.570291","type":"posted-content","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T22:40:34Z","timestamp":1701902434000},"source":"Crossref","is-referenced-by-count":10,"title":["Pseudomonas aeruginosa kills Staphylococcus aureus in a polyphosphate-dependent manner"],"prefix":"10.64898","author":[{"given":"Ritika","family":"Shah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Jankiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colton","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Livingston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8597-7416","authenticated-orcid":false,"given":"Jan-Ulrik","family":"Dahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023120906202747000_2023.12.05.570291v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)17745-9"},{"key":"2023120906202747000_2023.12.05.570291v1.2","first-page":"93","article-title":"The biogeography of polymicrobial infection","volume":"14","year":"2015","journal-title":"Nature Reviews Microbiology"},{"key":"2023120906202747000_2023.12.05.570291v1.3","doi-asserted-by":"publisher","DOI":"10.3391\/mbi.2017.8.1.01"},{"key":"2023120906202747000_2023.12.05.570291v1.4","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/ame2.12180","article-title":"A review of cystic fibrosis: Basic and clinical aspects","volume":"4","year":"2021","journal-title":"Animal Model Exp Med"},{"key":"2023120906202747000_2023.12.05.570291v1.5","doi-asserted-by":"crossref","unstructured":"Biswas L , G\u00f6tz F . 2022. 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