2.A.6.2.49
Multidrug resistance exporter, AcrABZ.  Exports tigecycline and many other drugs (Nielsen et al. 2014; Li et al. 2016; Yuhan et al. 2016; He et al. 2015; Bialek-Davenet et al. 2015).  AcrA-AcrB-AcrZ-TolC is a drug efflux protein complex with a broad substrate specificity. AcrZ (YbhT) binds to AcrB and is required for efflux of some but not all substrates, suggesting it may influence the specificity of drug export (Hobbs et al. 2012; Du et al. 2015). K. pneumoniae TolC plays a role in resistance towards most antibiotics, suggesting that it interacts with the AcrAB efflux pump (Iyer et al. 2019). Expression as well as missense mutations in the crrB gene promotes resistance to odilorhabdin class compounds including NOSO-502 (Pantel et al. 2021). A pyridylpiperazine efflux pump inhibitor, BDM91288, boosts in vivo antibiotic efficacy against K. pneumoniae.  Using cryo-EM, BDM91288 binding to the transmembrane region of K. pneumoniae AcrB was dwmostrated, validating the mechanism of action of this inhibitor. Oral administration of BDM91288 significantly potentiated the in vivo efficacy of levofloxacin treatment in a murine model of K. pneumoniae lung infection (Vieira Da Cruz et al. 2024).