The H-NS Regulator Plays a Role in the Stress Induced by Carbapenemase Expression in Acinetobacter baumannii

Abstract

Disruption of the histone-like nucleoid structuring protein (H-NS) was shown to affect the ability of Gram-negative bacteria to regulate genes associated with virulence, persistence, stress response, quorum sensing, biosynthesis pathways, and cell adhesion. Here, we used the expression of metallo-β-lactamases (MBLs), known to elicit envelope stress by the accumulation of toxic precursors in the periplasm, to interrogate the role of H-NS in Acinetobacter baumannii, together with other stressors. Using a multidrug-resistant A. baumannii strain, we observed that H-NS plays a role in alleviating the stress triggered by MBL toxic precursors and counteracts the effect of DNA-damaging agents, supporting its role in stress response. IMPORTANCE Carbapenem-resistant A. baumannii (CRAB) is recognized as one of the most threatening Gram-negative bacilli. H-NS is known to play a role in controlling the transcription of a variety of different genes, including those associated with the stress response, persistence, and virulence. In the present work, we uncovered a link between the role of H-NS in the A. baumannii stress response and its relationship with the envelope stress response and resistance to DNA-damaging agents. Overall, we posit a new role of H-NS, showing that H-NS serves to endure envelope stress and could also be a mechanism that alleviates the stress induced by MBL expression in A. baumannii. This could be an evolutionary advantage to further resist the action of carbapenems.

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

“…A previous analysis using metallo-β-lactamases (MBLs) and DNA-damaging agents as stressors 9 , showed that the AB5075 Δhns strain showed diminished ability to overcome stress 9 . Moreover, imipenem MICs of strains expressing the different MBLs, showed a detrimental impact on the antibiotic resistance phenotype in the Δ hns background 9 .…”

“…A previous analysis using metallo-β-lactamases (MBLs) and DNA-damaging agents as stressors 9 , showed that the AB5075 Δhns strain showed diminished ability to overcome stress 9 . Moreover, imipenem MICs of strains expressing the different MBLs, showed a detrimental impact on the antibiotic resistance phenotype in the Δ hns background 9 . In addition, the increased susceptibility to imipenem observed in both mutant strains can be explained in part by the significant increase in expression of carO (Supplementary Table S4 , and Fig.…”

“…A transcription factor of interest is H-NS, since it controls expression of many functions in bacteria, including adherence to biotic surfaces, quorum sensing, biofilm formation, and metabolism pathways 5 – 9 . In A. baumannii , H-NS regulates the expression of genes involved in a variety of biological processes like transport (e.g., autotransporters, type-VI secretion systems) and metabolism (e.g., phenylacetic acid degradation pathway) 7 .…”

Histone-like Nucleoid-structuring Protein (H-NS) Regulatory Role in Antibiotic Resistance in Acinetobacter Baumannii

“…A previous analysis using metallo-β-lactamases and DNA-damaging agents as stressors 9 , showed that the AB5075 Δhns strain showed diminished ability to overcome stress 9 . Moreover, imipenem MICs of strains expressing the different MBLs, showed a detrimental impact on the antibiotic resistance phenotype in the Δhns background 9 .…”

Multidrug Resistant Acinetobacter baumannii Biofilms: Evaluation of Phenotypic–Genotypic Association and Susceptibility to Cinnamic and Gallic Acids

“…In addition, the growth inhibitory activity of subinhibitory concentrations (1/2 and 1/4 MICs) of cinnamic and gallic acids was determined against these isolates. All determinations were performed as triplicates using untreated growth controls ( Huang et al, 2020 ; Li et al, 2021 ).…”