Unsaturated Fatty Acids Mediate Tolerance Stress Tolerance in Lactobacillales

Objectives: The order Lactobacillales encompasses some of the most important pathogens and commensals of the human microbiota including the streptococci, enterococci, and lactobacilli. Lactobacillales synthesize unsaturated fatty acids (UFAs) de novo via an isomerase enzyme, which is named FabM in Streptococcus and FabN in Enterococcus. Environmental stresses, including oxidative stress and acid stress, prompted an increase in the proportion of UFAs in the cell membranes of diverse Lactobacillales taxa including Streptococcus gordonii, Streptococcus salivarius, Streptococcus mutans, and Lactocaseibacillus casei. In S. mutans, specifically, these UFAs were crucial for survival against oxidative and acid stress, and inability to produce UFAs, via deletion of fabM, significantly reduced virulence of the organism in a rat model of dental caries.
Methods: In this study, ubiquity of UFA-mediated protection from oxidative and acid stresses across Lactobacillales was examined. Furthermore, the biological mechanism(s) underpinning this protection were investigated.
Results: Deletion of fabM in either Streptococcus mutans or Streptococcus pneumoniae significantly impaired growth, and prevented production of UFAs. In both species, these phenotypes could be at least partially rescued by providing exogenous UFAs. Furthermore deletion of fabM decreased the MIC of daptomycin for both S. mutans and S. pneumoniae.
Conclusions: Since many Lactobacillales must survive oxidative stress (generated by host immune cells or competing bacteria) and environmental acid stress (present in dental plaque, the skin, and the vagina) to persist in the microbiome and/or cause disease, the implications of these phenomena are significant.