The StkSR Two-Component System Influences Colistin Resistance in Acinetobacter baumannii

Giles, Sarah K; Stroeher, Uwe H.; Papudeshi, Bhavya; Edwards, Robert A.; Carlson-Jones, Jessica A. P.; Roach, Michael J.; Brown, Melissa H.

doi:10.3390/microorganisms10050985

Cited by 7 publications

(10 citation statements)

References 90 publications

(123 reference statements)

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“…Most TCS found in bacteria to date have the ability to regulate gene expression for antibiotic resistance [ 10 , 19 ], antibiotic production [ 20 ], virulence, biofilm formation and motility [ 21 ]. In addition, an increasing number of studies show that TCS are involved in metabolism; for example, the MxtR/ErdR TCS has been shown to be essential for acetate utilization in P. putida KT2440 [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of EmaSR in Ethanol Metabolism by Acinetobacter baumannii

Shu

Huang

Tsai

et al. 2022

IJMS

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“…Recently, a publication appeared that partially characterized amsSR in the clinical isolate 04117201 ( Giles et al, 2022 ). In that study, it was shown that AmsSR (named StkRS therein; an abbreviation of sticky) influenced colistin resistance through regulation of pmrCAB .…”

Section: Discussionmentioning

confidence: 99%

The novel two-component system AmsSR governs alternative metabolic pathway usage in Acinetobacter baumannii

et al. 2023

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In this study, we identify a novel two-component system in Acinetobacter baumannii (herein named AmsSR for regulator of alternative metabolic systems) only present in select gammaproteobacterial and betaproteobacterial species. Bioinformatic analysis revealed that the histidine kinase, AmsS, contains 14 predicted N-terminal transmembrane domains and harbors a hybrid histidine kinase arrangement in its C-terminus. Transcriptional analysis revealed the proton ionophore CCCP selectively induces PamsSR expression. Disruption of amsSR resulted in decreased intracellular pH and increased depolarization of cytoplasmic membranes. Transcriptome profiling revealed a major reordering of metabolic circuits upon amsR disruption, with energy generation pathways typically used by bacteria growing in limited oxygen being favored. Interestingly, we observed enhanced growth rates for mutant strains in the presence of glucose, which led to overproduction of pyruvate. To mitigate the toxic effects of carbon overflow, we noted acetate overproduction in amsSR-null strains, resulting from a hyperactive Pta-AckA pathway. Additionally, due to altered expression of key metabolic genes, amsSR mutants favor an incomplete TCA cycle, relying heavily on an overactive glyoxylate shunt. This metabolic reordering overproduces NADH, which is not oxidized by the ETC; components of which were significantly downregulated upon amsSR disruption. As a result, the mutants almost exclusively rely on substrate phosphorylation for ATP production, and consequently display reduced oxygen consumption in the presence of glucose. Collectively, our data suggests that disruption of amsSR affects the function of the aerobic respiratory chain, impacting the energy status of the cell, which in turn upregulates alternative metabolic and energy generation pathways.

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“…The TCS, AdeRS controls the RND efflux pumps like AdeABC, AdeFGH, and AdeIJK that showed their association with drug resistance against tetracyclines, aminoglycosides, tigecycline, erythromycin, and chloramphenicol (Giles et al, 2022). Another TCS, BaeSR, controls the expression of efflux pumps, whereas the BfmRS TCS regulate the morphology, attachment to biotic and abiotic surfaces, and biofilm expression .…”

Section: Regulation Of Virulencementioning

confidence: 99%

Deciphering the virulence factors, regulation, and immune response to Acinetobacter baumannii infection

Shadan¹,

Pathak

Ying

et al. 2023

Front. Cell. Infect. Microbiol.

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Deciphering the virulence factors, regulation, and immune response to Acinetobacter baumannii infectionAcinetobacter baumannii is a gram-negative multidrug-resistant nosocomial pathogen and a major cause of hospital acquired infetions. Carbapenem resistant A. baumannii has been categorised as a Priority1 critial pathogen by the World Health Organisation. A. baumannii is responsible for infections in hospital settings, clinical sectors, ventilator-associated pneumonia, and bloodstream infections with a mortality rates up to 35%. With the development of advanced genome sequencing, molecular mechanisms of manipulating bacterial genomes, and animal infection studies, it has become more convenient to identify the factors that play a major role in A. baumannii infection and its persistence. In the present review, we have explored the mechanism of infection, virulence factors, and various other factors associated with the pathogenesis of this organism. Additionally, the role of the innate and adaptive immune response, and the current progress in the development of innovative strategies to combat this multidrug-resistant pathogen is also discussed.

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The StkSR Two-Component System Influences Colistin Resistance in Acinetobacter baumannii

Cited by 7 publications

References 90 publications

Role of EmaSR in Ethanol Metabolism by Acinetobacter baumannii

Role of EmaSR in Ethanol Metabolism by Acinetobacter baumannii

The novel two-component system AmsSR governs alternative metabolic pathway usage in Acinetobacter baumannii

Deciphering the virulence factors, regulation, and immune response to Acinetobacter baumannii infection

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