AUTHOR=Biswas Lalitha , Götz Friedrich 

TITLE=Molecular Mechanisms of Staphylococcus and Pseudomonas Interactions in Cystic Fibrosis

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.824042

DOI=10.3389/fcimb.2021.824042

ISSN=2235-2988

ABSTRACT=<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 <italic>Staphylococcus aureus</italic> and Gram-negative <italic>Pseudomonas aeruginosa.</italic> While <italic>S. aureus</italic> is the main colonizing bacteria of the CF lungs during infancy and early childhood, its incidence declines thereafter and infections by <italic>P. aeruginosa</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, <italic>P. aeruginosa</italic> secretes small respiratory inhibitors like hydrogen cyanide, pyocyanin and quinoline <italic>N</italic>-oxides that block the electron transport pathway and suppress the growth of <italic>S. aureus</italic>. However, <italic>S. aureus</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 β-defensin (HBD) 2 and HBD3; and lactoferricin B. The interaction between <italic>P. aeruginosa</italic> and <italic>S. aureus</italic> is multifaceted. In mucoid <italic>P. aeruginosa</italic> strains, siderophores and rhamnolipids are downregulated thus enhancing the survival of <italic>S. aureus</italic>. Conversely, protein A from <italic>S. aureus</italic> inhibits <italic>P. aeruginosa</italic> biofilm formation while protecting both <italic>P. aeruginosa</italic> and <italic>S. aureus</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 <italic>S. aureus</italic> and <italic>P. aeruginosa</italic> in the CF lungs that could influence the disease outcome.</p>