Genetic regulation of the locus and its expression in clinical isolates of

R. Rosenblum (1) , E. Khan (2) , G. Gonzalez (3) , R. Hasan (2) , T. Schneiders (1)

1 Centre for Infection and Immunity
2 Department of Pathology and Microbiology
3 Facultad de Ciencias Biológicas

Tigecycline resistance has been attributed to overexpression and subsequent upregulation. The locus, originally identified in , has homologues in and spp. In this study, we identify in silico that the binding site is also present in spp. and that , and spp. share key regulatory elements in the control of the - locus. RACE (rapid amplification of cDNA ends) mapping indicated that there are two promoters from which - expression can be regulated in . Correspondingly, electrophoretic binding studies clearly showed that purified RamA and RamR proteins bind to both of these promoters. Hence, there appear to be two RamR binding sites within the - locus. Like MarA, RamA binds the promoter region, implying that it might be subject to autoregulation. We have identified changes within in geographically distinct clinical isolates of Intriguingly, levels of and expression were not uniformly affected by changes within the gene, thereby supporting the dual promoter finding. Furthermore, a subset of strains sustained no changes within the gene but which still overexpressed the - genes, strongly suggesting that a secondary regulator may control expression.

Mots clés: Klebsiella pneumoniae; romA; ramA; ramR; acrA; Tigecycline

Domaines: Microbiologie et Parasitologie

R. Rosenblum, E. Khan, G. Gonzalez, R. Hasan, T. Schneiders. Genetic regulation of the locus and its expression in clinical isolates of. International Journal of Antimicrobial Agents, 2011, ⟨10.1016/j.ijantimicag.2011.02.012⟩. ⟨hal-00703151⟩