Homologs of the Acinetobacter baumannii AceI Transporter Represent a New Family of Bacterial Multidrug Efflux Systems

Abstract

Multidrug efflux systems are a major cause of resistance to antimicrobials in bacteria, including those pathogenic to humans, animals, and plants. These proteins are ubiquitous in these pathogens, and five families of bacterial multidrug efflux systems have been identified to date. By using transcriptomic and biochemical analyses, we recently identified the novel AceI (Acinetobacter chlorhexidine efflux) protein from Acinetobacter baumannii that conferred resistance to the biocide chlorhexidine, via an active efflux mechanism. Proteins homologous to AceI are encoded in the genomes of many other bacterial species and are particularly prominent within proteobacterial lineages. In this study, we expressed 23 homologs of AceI and examined their resistance and/or transport profiles. MIC analyses demonstrated that, like AceI, many of the homologs conferred resistance to chlorhexidine. Many of the AceI homologs conferred resistance to additional biocides, including benzalkonium, dequalinium, proflavine, and acriflavine. We conducted fluorimetric transport assays using the AceI homolog from Vibrio parahaemolyticus and confirmed that resistance to both proflavine and acriflavine was mediated by an active efflux mechanism. These results show that this group of AceI homologs represent a new family of bacterial multidrug efflux pumps, which we have designated the proteobacterial antimicrobial compound efflux (PACE) family of transport proteins.

Chlorhexidine Induces VanA-Type Vancomycin Resistance Genes in Enterococci

“…Other highly upregulated genes include predicted metal transport systems and a predicted ABC transport system of unknown function that appears to be encoded by a mobile genetic element. The specific roles of these transport systems in the H-CHG stress response remain to be determined; possibilities include chlorhexidine efflux (note that a new family of chlorhexidine efflux proteins was recently identified for Gram-negative bacteria [67,68]), transport of metals to maintain redox balance in the cell, or transport of cell wall-related metabolites. Future studies will compare the transcriptomic response of E. faecium to H-CHG to that for CHG and sodium gluconate, which will help to determine which specific components of H-CHG are responsible for the transcriptional changes observed.…”

Antibiotic resistance in Burkholderia species

“…Bacterial genomes encode at least six efflux pump families (Fernandez and Hancock, 2012ß; Hassan et al, 2015; Nikaido and Pages, 2012; Piddock, 2006). These include: 1) The major facilitator (MFS) superfamily; 2) The resistance nodulation cell division (RND) family; 3) The small multidrug resistance (SMR) family; 4) The multi-drug and toxic compound extrusion (MATE) family; 5) The ATP-binding cassette (ABC) family; and 6) The proteobacterial antimicrobial compound efflux (PACE) family.…”

Beyond Antimicrobial Resistance: Evidence for a Distinct Role of the AcrD Efflux Pump in Salmonella Biology

“…Traditionally, Enterobacteriaceae such as Escherichia coli and Salmonella have five families of efflux pumps, the ABC and MFS superfamilies and the SMR, MATE, and RND families (1). Recently, the PACE family of efflux pumps was discovered in Acinetobacter species and is present in a range of Proteobacteria (2, 3). Salmonella enterica serovar Typhimurium (here, Salmonella Typhimurium) is used extensively as a model pathogen for many reasons, including easy genetic manipulation, good infection models, and relevance to other pathogens (4, 5).…”