Systematic analyses identify modes of action of ten clinically relevant biocides and antibiotic antagonism in Acinetobacter baumannii

Concerns exist that widespread use of antiseptic or disinfectant biocides could contribute to the emergence and spread of multidrug-resistant bacteria. To investigate this, we performed transposon-directed insertion-site sequencing (TraDIS) on the multidrug-resistant pathogen, Acinetobacter baumannii, exposed to a panel of ten structurally diverse and clinically relevant biocides. Multiple gene targets encoding cell envelope or cytoplasmic proteins involved in processes including fatty acid biogenesis, multidrug efflux, the tricarboxylic acid cycle, cell respiration and cell division, were identified to have effects on bacterial fitness upon biocide exposure, suggesting that these compounds may have intracellular targets in addition to their known effects on the cell envelope. As cell respiration genes are required for A. baumannii fitness in biocides, we confirmed that sub-inhibitory concentrations of the biocides that dissipate membrane potential can promote A. baumannii tolerance to antibiotics that act intracellularly. Our results support the concern that residual biocides might promote antibiotic resistance in pathogenic bacteria.

Automated summary

Concerns have been raised regarding the potential contribution of antiseptic or disinfectant biocides to the emergence and spread of multidrug-resistant bacteria. This study used transposon-directed insertion-site sequencing to investigate the effects of a panel of biocides on the fitness of the multidrug-resistant pathogen Acinetobacter baumannii. The results suggest that these biocides may have intracellular targets in addition to their known effects on the cell envelope, and that residual biocides could promote antibiotic resistance in pathogenic bacteria.