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

Abstract

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.

Genomic Characteristics and Pan-Genome Analysis of Rhodococcus equi

“…Among the three mycosyl transferase genes of Mycobacterium tuberculosis, only the mutation of fbpA was considered to weaken the growth of this species in macrophages. Fade14 gene was also predicted in this study, FadE14 is part of an iron and IdeR repressible operon which produces a polycistronic message encoding FadE14, FadD33 and an acyl carrier protein (acp), in Mycobacterium smegmatis, FadE14 were necessary for wild-type mycobactin production (Rodgers et al, 2021). The ability to metabolize fatty acids seems to be crucial to the toxicity of Streptococcus equi.…”

Human serum albumin (HSA) regulates the expression of histone-like nucleoid structure protein (H-NS) in Acinetobacter baumannii

“…Transcriptome analysis of A. baumannii AB5075 and AB5075 Δhns cultured in LB broth revealed a differential expression profile of 183 genes 22 . When A. baumannii AB5075 was cultured in LB broth with or without HSA there were 30 genes differentially expressed (Table S1 ).…”

“…Phenotypic modifications in quorum sensing were assessed determining levels of acyl-homoserine lactone (AHL) using the Agrobacterium tumefaciens -based solid plate assays 28 , 29 . Rodgers et al demonstrated that the supernatants from A. baumannii AB5075 or AB5075 Δhns produced similar intensity of color, likely caused by an increase in both AHL synthesis (quorum sensing) and lactonase activity (quorum quenching) in AB5075 Δhns strain 22 . To study the effect of HSA on AHL secretion into the surrounding medium, A. baumannii AB5075, AB5075 Δhns, and the strains complemented with pMBLe- hns were cultured in different conditions before assessing the AHL concentration in the growth medium.…”

“…H-NS is a nucleoid-associated protein that binds DNA in a relatively nonspecific manner (it shows preference for AT-rich and curved regions) and alters its topology, which modifies levels of transcription. The effects of H-NS in A. baumannii have not been thoroughly studied 17 , 20 , 22 . An early analysis found that an A. baumannii mutant containing a disrupted hns gene was modified in the expression of several virulence genes such as those associated with the autotransporter Ata, the type VI secretion system, a type I pilus cluster, the acetoin metabolism, and phenylacetic acid degradation 17 .…”

“…In A. baumannii the H-NS protein, a global transcriptional repressor in many Gram-negative bacteria 16 – 19 , plays a major role in persistence and expression of virulence-associated genes 17 , 20 , stress induced by carbapenemase expression 21 , as well as expression of genes associated with antibiotic resistance, biofilm formation, and quorum sensing 22 . H-NS may also be necessary for natural competence in A. baumannii as an hns null mutant showed significantly lower expression levels of genes related to acquisition of DNA from the environment 23 .…”