Acinetobacter spp. have become of increased clinical importance as studies have shown the antimicrobial resistant potential of these species. Efflux pumps can lead to reduced susceptibility to a variety of antibiotics and are present in large number across Acinetobacter spp. There are six families of efflux pumps that have been shown to be of clinical relevance: the Major Facilitator Superfamily (MFS), Small Multidrug Resistance (SMR) family, ATP-binding cassette (ABC) family, Multidrug and Toxic Compound Extrusion (MATE) family, Proteobacterial Antimicrobial Compound Efflux (PACE) family and Resistance-Nodulation-Division (RND) family. A lot of work has been done on understanding and characterizing the roles that these efflux pumps play in relation to antimicrobial resistance and the physiology of these bacteria. RND efflux pumps, with their expansive substrate profiles, are a major component of Acinetobacter spp. antimicrobial resistance. New discoveries over the last decade have shed a lot of light on to the complex regulation of these efflux pumps leading to greater understanding and potential of slowing the reduced susceptibility seen by these bacterial species.

Iron is an essential element for survival of most organisms. One mechanism of host defense is to tightly chelate iron to several proteins to limit its extracellular availability.

With the current arsenal of antibiotics increasingly becoming ineffective against bacteria, there is an increasing interest in the possibility of using previously approved non-antibiotic drugs as antimicrobials. Statins have recently been investigated for their antimicrobial activity and their ability to potentially synergize with current treatment options. Atorvastatin had been shown previously to be the most promising candidate for effectivity against Acinetobacter baumannii ATCC17978. In this study, we tested atorvastatin for its activity against an extensively drug-resistant (XDR) strain A. baumannii AB030. However, our data show that atorvastatin has no effect A. baumannii AB030. Intriguingly, atorvastatin was also ineffective against our laboratory’s A. baumannii ATCC17978. This lack of atorvastatin activity against A. baumannii ATCC17978 cannot be attributed to RND efflux pumps as a strain deficient in the three most clinically relevant RND efflux systems in A. baumannii showed no change in susceptibility compared to its parent strain ATCC17978. Further, atorvastatin failed to potentiate the activity of tobramycin and ciprofloxacin. While it is not clear to us why atorvastatin is not active against A. baumannii ATCC17978 used in our study, our study shows that evaluation of compounds for their antibacterial activity should involve multiple strains to account for strain-to-strain variation.