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

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. 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.

Automated summary

The adaptation of Pseudomonas aeruginosa to the antiseptic octenidine is characterized by synergistic changes in efflux and plasma membrane composition, primarily through mutations in SmvR, SmvA, PssA, and PgsA. This adaptation leads to significantly increased octenidine tolerance in both laboratory and simulated clinical settings, with stable mutations and specific gene deletions associated with higher level, synergistic tolerance.