RND/HAE-1 members in the Pseudomonadota phylum: exploring multidrug resistance

The hydrophobe/amphiphile efflux-1 (HAE-1) family, part of the Resistance-Nodulation-Division (RND) superfamily, plays a critical role in the development of multidrug resistance (MDR) in bacteria. Known for its broad substrate transport capacity, this family of efflux pumps can actively expel a wide range of molecules, including antibiotics, salts, and dyes, thereby reducing the intracellular concentration of toxic substances. These transporters, which form efflux systems, are primarily found in bacteria within the phylum Pseudomonadota (Proteobacteria), where they are strongly associated with increased resistance and enhanced virulence, thus contributing to bacterial survival in hostile environments. In addition, efflux systems are composed of two other protein components: Membrane Fusion Proteins (MFPs) and Outer Membrane Factors (OMFs). Notably, several bacterial species identified by the World Health Organization (WHO) as urgent priorities for new antibiotic development, such as Escherichia coli and Pseudomonas aeruginosa, have well-studied HAE-1 efflux systems, such as AcrAB-TolC and MexAB-OprM. These systems efficiently transport molecules from the periplasm to the extracellular space, facilitating bacterial persistence. In this review, we examined the current knowledge of HAE-1 efflux transporters and their roles in the physiology and survival of bacteria in the Pseudomonadota phylum.