Mechanisms of 10-Hydroxyoctadecanoic acid resistance in Streptococcus pneumoniae

ABSTRACT Profiles of human nasal colonization consistently demonstrate thatStaphylococcus aureusandStreptococcus pneumoniaecan co-exist in the nasopharynx. Several studies have demonstrated the antagonist relationship between the two organisms via several molecular mechanisms including competition for nutrients as well as via direct killing by hydrogen peroxide. During nasal colonization, the pneumococcus is in direct contact with the fatty acidh18:0, which is released into the extracellular environment byS. aureus. We report thath18:0 is specifically toxic to the pneumococcus amongst the pathogenic streptococci, providing a unique mechanism for interspecies competition during colonization. Exposure of cells toh18:0 revealed thatS. pneumoniaecould rapidly adapt to and overcome the observed toxicity. Whole genome analysis revealed the mechanism underlying this resistance being linked to a truncation of a glycosyltransferase in the capsule biosynthesis locus and a genomic inversion in the phase variation locus, leading to altered cell surface charge and membrane lipid composition. These physiological differences in the resistant isolates may aid in repelling toxic, charged fatty acids such ash18:0 from the cell membrane. IMPORTANCE The pneumococcus andS. aureusare two of the most well-characterized residents of the human nasopharynx; yet much remains unknown regarding how the two bacteria interact. Here, we describe the potential ofS. aureus–producedh18:0, whose function and biological impact are still being described, to act as an inter-species competition molecule againstS. pneumoniae, and how the pneumococcus can adapt to overcome its toxicity.