Histone-like nucleoid-structuring protein (H-NS) regulatory role in antibiotic resistance in Acinetobacter baumannii

RODGERS, DEJA; LE, CASIN; PIMENTEL, CAMILA; TUTTOBENE, MARISEL R.; SUBILS, TOMÁS; ESCALANTE, JENNY; NISHIMURA, BRENT; VESCOVI, ELEONORA GARCÍA; SIEIRA, RODRIGO; BONOMO, ROBERT A.; TOLMASKY, MARCELO E.; RAMIREZ, MARIA SOLEDAD

Scientific Reports

Nature Portfolio

Año: 2021 vol. 11

In the multidrug-resistant (MDR) pathogen Acinetobacter baumannii the global repressor H-NS wasshown to modulate the expression of genes involved in pathogenesis and stress response. In addition, H-NS inactivation results in 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 bring us one step closer to understanding the regulatory role of hns to combat A. baumannii infections.