Mechanisms of 10-Hydroxyoctadecanoic acid resistance in Streptococcus pneumoniae

Profiles of human nasal colonization consistently demonstrate that Staphylococcus aureus and Streptococcus pneumoniae can 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 acid h 18:0, which is released into the extracellular environment by S. aureus . We report that h 18:0 is specifically toxic to the pneumococcus amongst the pathogenic streptococci, providing a unique mechanism for interspecies competition during colonization. Exposure of cells to h 18:0 revealed that S. pneumoniae could 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 as h 18:0 from the cell membrane.

The pneumococcus and S. aureus are 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 of S. aureus- produced h 18:0, whose function and biological impact are still being described, to act as an inter-species competition molecule against S. pneumoniae , and how the pneumococcus can adapt to overcome its toxicity.