Pseudomonas aeruginosa adapts to octenidine via a combination of efflux and membrane remodelling

Pseudomonas aeruginosa is an opportunistic pathogen capable of stably adapting to the antiseptic octenidine by an unknown mechanism. Here we characterise this adaptation, both in the laboratory and a simulated clinical setting, and identify a novel antiseptic resistance mechanism. In both settings, 2 to 4-fold increase in octenidine tolerance was associated with stable mutations and a specific 12 base pair deletion in a putative Tet-repressor family gene (smvR), associated with a constitutive increase in expression of the Major Facilitator Superfamily (MFS) efflux pump SmvA. Adaptation to higher octenidine concentrations led to additional stable mutations, most frequently in phosphatidylserine synthase pssA and occasionally in phosphatidylglycerophosphate synthase pgsA genes, resulting in octenidine tolerance 16- to 256-fold higher than parental strains. Metabolic changes were consistent with mitigation of oxidative stress and altered plasma membrane composition and order. Mutations in SmvAR and phospholipid synthases enable higher level, synergistic tolerance of octenidine.
Bock et al. characterise the adaptation of Pseudomonas aeruginosa to the antiseptic octenidine, using whole genome sequencing, gene expression studies and metabolomics. They attribute this increased tolerance to synergistic changes in efflux and plasma membrane composition via mutations in SmvR, the regulator of MFS efflux pump SmvA, and in phospholipid pathway proteins PssA and PgsA.