# Mechanisms of 10-hydroxyoctadecanoic acid resistance in Streptococcus pneumoniae

## TL;DR

Streptococcus pneumoniae can resist a toxic fatty acid produced by Staphylococcus aureus by altering its cell membrane.

## Contribution

The paper identifies genetic and physiological adaptations in S. pneumoniae that confer resistance to h18:0.

## Key findings

- h18:0 is toxic to S. pneumoniae but not to other pathogenic streptococci.
- Resistance in S. pneumoniae is linked to a glycosyltransferase truncation and genomic inversion.
- Resistant isolates have altered cell surface charge and membrane lipid composition.

## Abstract

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 h18:0, which is released into the extracellular environment by S. aureus. We report that h18:0 is specifically toxic to the pneumococcus among the pathogenic streptococci, providing a unique mechanism for interspecies competition during colonization. Exposure of cells to h18:0 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 h18:0 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 h18:0, whose function and biological impact are still being described, to act as an interspecies competition molecule against S. pneumoniae, and how the pneumococcus can adapt to overcome its toxicity.