Rodrigo Sieira, Brent Nishimura, Camila Pimentel, Maria Soledad Ramirez, Robert A. Bonomo, Tomas Subils, Marcelo E. Tolmasky, Eleonora García Véscovi, Deja Rodgers, Jenny Escalante, Casin Le, and Marisel R. Tuttobene
In the multidrug resistant (MDR) pathogen Acinetobacter baumannii the global repressor H-NS was shown to modulate the expression of genes involved in pathogenesis and stress response. In addition, H-NS inactivation results in an increased resistance to colistin, and in a hypermotile phenotype an altered stress response. To further contribute to the knowledge of this key transcriptional regulator in A. baumannii behavior, we studied the role of H-NS in antimicrobial resistance. Using two well characterized A. baumannii model strains with distinctive resistance profile and pathogenicity traits (AB5075 and A118), complementary transcriptomic and phenotypic approaches were used to study the role of H-NS in antimicrobial resistance, biofilm and quorum sensing gene expression. An increased expression of genes associated with β-lactam resistance, aminoglycosides, quinolones, chloramphenicol, trimethoprim and sulfonamides resistance in the Δhns mutant background was observed. Genes codifying for efflux pumps were also up-regulated, with the exception of adeFGH. The wild-type transcriptional level was restored in the complemented strain. In addition, the expression of biofilm related genes and biofilm production was lowered when the transcriptional repressor was absent. The quorum network genes aidA, abaI, kar and fadD were up-regulated in Δhns mutant strains. Overall, our results showed the complexity and scope of the regulatory network control by H-NS (genes involved in antibiotic resistance and persistence). These observations brings us one step closer to understanding the regulatory role of hns to combat A. baumannii infections. Fil: Rodgers, Deja. California State University Fullerton. College of Natural Sciences and Mathematics. Department of Biological Science. Center for Applied Biotechnology Studies; United States. Fil: Le, Casin. California State University Fullerton. College of Natural Sciences and Mathematics. Department of Biological Science. Center for Applied Biotechnology Studies; United States. Fil: Pimentel, Camila. California State University Fullerton. College of Natural Sciences and Mathematics. Department of Biological Science. Center for Applied Biotechnology Studies; United States. Fil: Tuttobene, Marisel Romina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Biología Molecular; Argentina. Fil: Tuttobene, Marisel Romina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina. Fil: Subils, Tomás. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos de Rosario (IPROBYQ-CONICET); Argentina. Fil: Escalante, Jenny. California State University Fullerton. College of Natural Sciences and Mathematics. Department of Biological Science. Center for Applied Biotechnology Studies; United States. Fil: Nishimura, Brent. California State University Fullerton. College of Natural Sciences and Mathematics. Department of Biological Science. Center for Applied Biotechnology Studies; United States. Fil: Vescovi, Eleonora García. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina. Fil: Sieira, Rodrigo. Fundación Instituto Leloir (IIBBA-CONICET); Argentina. Fil: Bonomo, Robert A. Louis Stokes Cleveland. Department of Veterans Affairs Medical Center. Research Service and GRECC; United States. Fil: Bonomo, Robert A. Case Western Reserve University School of Medicine. Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, Proteomics and Bioinformatics; United States. Fil: Bonomo, Robert A. CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES); United States.