{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T05:01:17Z","timestamp":1792558877310,"version":"4.5.0"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Cystic fibrosis (CF) is an autosomal recessive genetic disorder that is characterized by recurrent and chronic infections of the lung predominantly by the opportunistic pathogens, Gram-positive <jats:italic>Staphylococcus aureus<\/jats:italic> and Gram-negative <jats:italic>Pseudomonas aeruginosa.<\/jats:italic> While <jats:italic>S. aureus<\/jats:italic> is the main colonizing bacteria of the CF lungs during infancy and early childhood, its incidence declines thereafter and infections by <jats:italic>P. aeruginosa<\/jats:italic> become more prominent with increasing age. The competitive and cooperative interactions exhibited by these two pathogens influence their survival, antibiotic susceptibility, persistence and, consequently the disease progression. For instance, <jats:italic>P. aeruginosa<\/jats:italic> secretes small respiratory inhibitors like hydrogen cyanide, pyocyanin and quinoline <jats:italic>N<\/jats:italic>-oxides that block the electron transport pathway and suppress the growth of <jats:italic>S. aureus<\/jats:italic>. However, <jats:italic>S. aureus<\/jats:italic> survives this respiratory attack by adapting to respiration-defective small colony variant (SCV) phenotype. SCVs cause persistent and recurrent infections and are also resistant to antibiotics, especially aminoglycosides, antifolate antibiotics, and to host antimicrobial peptides such as LL-37, human \u03b2-defensin (HBD) 2 and HBD3; and lactoferricin B. The interaction between <jats:italic>P. aeruginosa<\/jats:italic> and <jats:italic>S. aureus<\/jats:italic> is multifaceted. In mucoid <jats:italic>P. aeruginosa<\/jats:italic> strains, siderophores and rhamnolipids are downregulated thus enhancing the survival of <jats:italic>S. aureus<\/jats:italic>. Conversely, protein A from <jats:italic>S. aureus<\/jats:italic> inhibits <jats:italic>P. aeruginosa<\/jats:italic> biofilm formation while protecting both <jats:italic>P. aeruginosa<\/jats:italic> and <jats:italic>S. aureus<\/jats:italic> from phagocytosis by neutrophils. This review attempts to summarize the current understanding of the molecular mechanisms that drive the competitive and cooperative interactions between <jats:italic>S. aureus<\/jats:italic> and <jats:italic>P. aeruginosa<\/jats:italic> in the CF lungs that could influence the disease outcome.<\/jats:p>","DOI":"10.3389\/fcimb.2021.824042","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T05:30:16Z","timestamp":1641447016000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":83,"title":["Molecular Mechanisms of Staphylococcus and Pseudomonas Interactions in Cystic Fibrosis"],"prefix":"10.3389","volume":"11","author":[{"given":"Lalitha","family":"Biswas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"G\u00f6tz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1126\/science.1712984","article-title":"Demonstration That Cftr Is a Chloride Channel by Alteration of Its Anion Selectivity","volume":"253","author":"Anderson","year":"1991","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0135579","DOI":"10.1371\/journal.pone.0135579","article-title":"Impact of the Regulators SigB, Rot, SarA and sarS on the Toxic Shock Tst Promoter and TSST-1 Expression in Staphylococcus Aureus","volume":"10","author":"Andrey","year":"2015","journal-title":"PloS One"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00538-16","article-title":"Staphylococcus Aureus Protein A Mediates Interspecies Interactions at the Cell Surface of Pseudomonas Aeruginosa","volume":"7","author":"Armbruster","year":"2016","journal-title":"Mbio"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e89614","DOI":"10.1371\/journal.pone.0089614","article-title":"Adaptation of Pseudomonas Aeruginosa in Cystic Fibrosis Airways Influences Virulence of Staphylococcus Aureus In Vitro and Murine Models of Co-Infection","volume":"9","author":"Baldan","year":"2014","journal-title":"PloS One"},{"key":"B5","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.toxicon.2018.01.004","article-title":"Immuno-Modulatory Functions of the Type-3 Secretion System and Impacts on the Pulmonary Host Defense: A Role for ExoS of Pseudomonas Aeruginosa in Cystic Fibrosis","volume":"143","author":"Belmadi","year":"2018","journal-title":"Toxicon"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2012.00044","article-title":"Comparative Genomics of the Staphylococcus Intermedius Group of Animal Pathogens","volume":"2","author":"Ben Zakour","year":"2012","journal-title":"Front. 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