Technology Development Group, National Infection Service, PHE Porton, Salisbury, UK.
Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Science, King's College London, London, UK.
Commun Biol. 2021 Sep 9;4(1):1058. doi: 10.1038/s42003-021-02566-4.
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.
铜绿假单胞菌是一种机会性病原体，能够通过未知机制稳定地适应防腐剂奥替尼啶。在这里，我们在实验室和模拟临床环境中对这种适应性进行了描述，并确定了一种新的抗防腐剂耐药机制。在这两种情况下，奥替尼啶耐受性增加 2 至 4 倍与假定的 Tet 阻遏物家族基因（smvR）中的稳定突变和特定的 12 碱基对缺失相关，这与主要易化剂超家族（MFS）外排泵 SmvA 的组成性表达增加有关。适应更高的奥替尼啶浓度导致了额外的稳定突变，最常见于磷脂酰丝氨酸合酶 pssA，偶尔在磷脂酰甘油磷酸合酶 pgsA 基因中，导致奥替尼啶耐受性比亲本菌株高 16 至 256 倍。代谢变化与缓解氧化应激以及改变质膜组成和有序性一致。SmvAR 和磷脂合成酶的突变使奥替尼啶的耐受力更高，协同作用更强。
