Acinetobacter baumannii Regulates Its Stress Responses via the BfmRS Two-Component Regulatory System

Palethorpe, Samantha; Farrow, John M.; Wells, Greg; Milton, Morgan E.; Actis, Luis A.; Cavanagh, John; Pesci, Everett C.

doi:10.1128/jb.00494-21

Cited by 31 publications

(66 citation statements)

References 77 publications

(117 reference statements)

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“…In fact, we show that modulation of motility by light in A. baumannii V15 depends on both components of this system, BfmR and BfmS. Our working model is compatible with BfmR acting as a repressor of motility most likely in its phosphorylated state, which is counteracted by BfmS in the dark most probably by dephosphorylation 11 , setting thus a differential response to illumination that is lost in the absence of the repressor, independently of the light condition (Fig. 6).…”

Section: Discussionsupporting

confidence: 69%

“…In fact, analyses of RNAseq data performed in ATCC 17978 strain by Geisinger et al, 2018, show that bfmS expression is reduced in the ΔbfmR mutant (FCbfmR in ΔbfmS = 1.467; FCbfmS in ΔbfmR = 0,0308), indicating that BfmR acts as an activator of bfmRS expression. Consistently, it has been shown that BfmR can activate its own expression, and phosphorylation is required for autoinduction 11 . As control, the ΔbfmRS mutant harboring the empty pUC_AcORI_Ptac_TER_lacIq2 plasmid 12 , which is referred to as pE, behaved as ΔbfmRS, i.e., does not photoregulate and moved both under blue light and in the dark (Fig.…”

Section: Resultsmentioning

confidence: 59%

“…BfmRS is a two component system described in A. baumannii, showing atypical characteristics mainly because the sensor, BfmS, appears to antagonize the functioning of the response regulator, BfmR, by dephosphorylation in response to yet unknown signals 11 .…”

Section: Introductionmentioning

confidence: 99%

“…Recent results strongly suggest that phosphorylated BfmR (BfmR ~ P) is the active form of this response regulator that directly in uences gene expression. BfmR can autophosphorylate in vitro using small phosphodonors such as acetylphosphate 11 . BfmS contains two membrane-spanning regions common to sensor kinases, and a C-terminal, cytoplasmic histidine kinase catalytic domain 11 .…”

Section: Introductionmentioning

confidence: 99%

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BfmRS encodes a regulatory system involved in light signal transduction in the human pathogen Acinetobacter baumannii.

Mora

Giordano

Permingeat

et al. 2022

Preprint

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We have previously shown that Acinetobacter baumannii as well as other relevant clinical bacterial pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, perceive and respond to light at 37°C, the normal temperature in mammal hosts. In this work, we present evidence indicating that the two-component system BfmRS transduces a light signal in A. baumannii at this temperature, showing selective involvement of the BfmR and BfmS components depending on the specific cellular process. In fact, both BfmR and BfmS participate in modulation of motility by light, while only BfmR is involved in light regulation of desiccation tolerance in this microorganism. Neither BfmR nor BfmS contain a photoreceptor domain and then most likely, the system is sensing light indirectly. Intriguingly, this system inhibits blsA expression at 37°C, explaining previous results indicating that BlsA only functions at moderate temperatures 1–3, and thus governing the response to light at 37°C. Overall, we provide experimental evidence on a new biological function of this multifaceted system that broadens our understanding of A. baumannii’s physiology and responses to light.

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Section: Discussionsupporting

confidence: 69%

Section: Resultsmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

BfmRS encodes a regulatory system involved in light signal transduction in the human pathogen Acinetobacter baumannii.

Mora

Giordano

Permingeat

et al. 2022

Preprint

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“…Two-component systems (TCSs) also play an important part in A. baumannii stress resistance, biofilm formation, and drug resistance, primarily by regulating the signal transduction of environmental stimuli. At least 7 TCSs have been described in A. baumannii thus far , including AdeSR [ 5 ], BaeSR [ 6 ], BfmSR [ 7 ], GasSA [ 8 ], PmrAB [ 9 ], StkSR [ 10 ], and A1S_2811 of A. baumannii ATCC 17978 [ 11 ], and have been associated with aromatic compound catabolism, motility, biofilm formation, virulence, and drug resistance [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Role of EmaSR in Ethanol Metabolism by Acinetobacter baumannii

Shu

Huang

Tsai

et al. 2022

IJMS

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Acinetobacter baumannii is a well-known nosocomial pathogen that can survive in different environments through the use of intricate networks to regulate gene expression. Two-component systems (TCS) form an important part of such regulatory networks, and in this study, we describe the identification and characterization of a novel EmaSR TCS in A. baumannii. We constructed a Tn5-tagged mutagenesis library, from which an emaS sensor kinase gene and emaR response regulator gene were identified. We found that emaS/emaR single-mutants and double-mutants were unable to replicate in M9 medium with 1% ethanol as the single carbon source. Motility and biofilm formation were negatively affected in double-mutants, and transcriptomic analysis showed that mutation of emaSR dysregulated genes required for carbon metabolism. In addition, emaS/emaR single-mutants and double-mutants were unable to survive in acetic acid- and sodium acetate-containing medium, indicating that the EmaSR TCS is also important for acetate metabolism. Furthermore, virulence against Galleria mellonella was diminished in emaS/emaR single- and double-mutants. Taken together, these results show that this novel EmaSR TCS is involved in the regulation of A. baumannii ethanol metabolism and acetate metabolism, with important implications on motility, biofilm formation, and virulence if mutated. Further research on the underlying mechanisms is warranted.

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Co-regulation of biofilm formation and antimicrobial resistance in Acinetobacter baumannii: from mechanisms to therapeutic strategies

Mendes,

Combo,

Allain

et al. 2023

Eur J Clin Microbiol Infect Dis

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In recent years, multidrug-resistant Acinetobacter baumannii has emerged globally as a major threat to the healthcare system. It is now listed by the World Health Organization as a priority one for the need of new therapeutic agents. A. baumannii has the capacity to develop robust biofilms on biotic and abiotic surfaces. Biofilm development allows these bacteria to resist various environmental stressors, including antibiotics and lack of nutrients or water, which in turn allows the persistence of A. baumannii in the hospital environment and further outbreaks. Investigation into therapeutic alternatives that will act on both biofilm formation and antimicrobial resistance (AMR) is sorely needed. The aim of the present review is to critically discuss the various mechanisms by which AMR and biofilm formation may be co-regulated in A. baumannii in an attempt to shed light on paths towards novel therapeutic opportunities. After discussing the clinical importance of A. baumannii, this critical review highlights biofilm-formation genes that may be associated with the co-regulation of AMR. Particularly worthy of consideration are genes regulating the quorum sensing system AbaI/AbaR, AbOmpA (OmpA protein), Bap (biofilm-associated protein), the two-component regulatory system BfmRS, the PER-1 β-lactamase, EpsA, and PTK. Finally, this review discusses ongoing experimental therapeutic strategies to fight A. baumannii infections, namely vaccine development, quorum sensing interference, nanoparticles, metal ions, natural products, antimicrobial peptides, and phage therapy. A better understanding of the mechanisms that co-regulate biofilm formation and AMR will help identify new therapeutic targets, as combined approaches may confer synergistic benefits for effective and safer treatments.

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Acinetobacter baumannii Regulates Its Stress Responses via the BfmRS Two-Component Regulatory System

Cited by 31 publications

References 77 publications

BfmRS encodes a regulatory system involved in light signal transduction in the human pathogen Acinetobacter baumannii.

BfmRS encodes a regulatory system involved in light signal transduction in the human pathogen Acinetobacter baumannii.

Role of EmaSR in Ethanol Metabolism by Acinetobacter baumannii

Co-regulation of biofilm formation and antimicrobial resistance in Acinetobacter baumannii: from mechanisms to therapeutic strategies

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