The role of Acinetobacter baumannii response regulator BfmR in pellicle formation and competitiveness via contact-dependent inhibition system

Abstract

BackgroundAcinetobacter baumannii is one of the most important opportunistic pathogens responsible for hospital acquired infections. It displays multi-drug resistance profile and has the ability to colonize surfaces and persist under harsh conditions. A. baumannii two-component signal transduction system BfmRS, consisting of response regulator BfmR and sensor kinase BfmS, has been implicated in the control of various virulence-related traits and has been suggested to act as a global modulator of A. baumannii physiology.ResultsHere, we assessed the role of BfmR regulator in pellicle formation and bacterial competition, features important for the establishment of A. baumannii in clinical environment. We show that BfmR is required for the pellicle formation of A. baumannii, as ΔbfmRS mutant lacked this phenotype. The loss of bfmRS also greatly reduced the secretion of A. baumannii Hcp protein, which is a component of T6SS secretion system. However, T6SS-mediated killing phenotype was not impaired in ΔbfmRS mutant. On the contrary, the same mutation resulted in the transcriptional activation of contact-dependent inhibition (CDI) system, which A. baumannii used to inhibit the growth of another clinical A. baumannii strain and a closely related species Acinetobacter baylyi.ConclusionsThe obtained results indicate that BfmR is not only required for the pellicle phenotype induction in A. baumannii, but also, due to the down-regulation of a CDI system, could allow the incorporation of other A. baumannii strains or related species, possibly increasing the likelihood of the pathogens’ survival.

Efflux pump inhibitory activity of biologically synthesized silver nanoparticles against multidrug‐resistant Acinetobacter baumannii clinical isolates

“…The two‐component system is the signal transduction pathway in bacteria that responds to the environmental conditions [15]. The AdeR protein (regulator) contains 228 amino acids, and it is a transcriptional regulator, and the shorter protein AdeS (sensor kinase) exhibits the bacterial histidine kinase activity [16].…”

Capsule Protects Acinetobacter baumannii From Inter-Bacterial Competition Mediated by CdiA Toxin

“…A. baumannii and E. coli strains were grown in Luria-Bertani (LB) media or Tryptic soy broth (TSB) (Oxoid). All parent A. baumannii strains used in the work were previously characterized and are listed in Supplementary Table S1 ( Povilonis et al, 2013 ; Krasauskas et al, 2019 ; Skerniškytė et al, 2019 ). The strains were classified according to Pasteur scheme for 7-gene multilocus sequence typing ( Diancourt et al, 2010 ) and were determined to belong to sequence type (ST) 2 ( A. baumannii II-c, A. baumannii II-a, and A. baumannii II-a1) and ST1422 for A. baumannii V15.…”

“…genomes encode up to two CDI systems, which can be separated into two classes by size and that there is a great heterogeneity within the sequences ( De Gregorio et al, 2019 ). Our recent study shed some light on the regulatory mechanisms of these systems by showing that the two-component system BfmRS negatively regulates a CDI system from a clinical A. baumannii V15 strain ( Krasauskas et al, 2019 ). In this study, by using genotypically different clinical A. baumannii strains with different surface related properties, we show that capsule is required for the protection against CDI-mediated activity.…”

Proteomic and Systematic Functional Profiling Unveils Citral Targeting Antibiotic Resistance, Antioxidant Defense, and Biofilm-Associated Two-Component Systems of Acinetobacter baumannii To Encumber Biofilm and Virulence Traits

“…Additionally, BfmR supports the survival of A. baumannii in human serum and was also assessed by a blood survival assay, and the results showed that citral treatment enhanced the sensitivity of A. baumannii to the host immune system compared to the control sample (Fig. 12C) (42)(43)(44). The H-NS histone family protein regulates various functions of bacteria, such as the expression of outer membrane proteins, motility, biofilm formation, and extracellular polysaccharide synthesis (45,46).…”