The sensor kinase BfmS mediates virulence in Acinetobacter baumannii

Liou, Ming-Li; Soo, Po-Chi; Ling, Siao-Ru; Kuo, Han-Yueh; Tang, Chuan Yi; Chang, Kai‐Chih

doi:10.1016/j.jmii.2012.12.004

Cited by 92 publications

(78 citation statements)

References 24 publications

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“…Further assessments will be required to verify if this phenotype is maintained across other A. baumannii isolates and extends to other structurally-similar compounds. It has been found previously, that the introduction of shuttle vectors expressing WT copies of genes in trans do not restore resistance profiles back to WT levels as also seen in this study [45][46][47][48]. Using qRT-PCR, adeS was expressed at low levels in WT cells even after pentamidine shock (data not shown).…”

Section: Discussionsupporting

confidence: 63%

Resistance to pentamidine is mediated by AdeAB, regulated by AdeRS, and influenced by growth conditions inAcinetobacter baumanniiATCC 17978

Adams

Stroeher

Hassan

et al. 2018

Preprint

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In recent years, effective treatment of infections caused by Acinetobacter baumannii has become challenging due to the ability of the bacterium to acquire or up-regulate antimicrobial resistance determinants. Two component signal transduction systems are known to regulate expression of virulence factors including multidrug efflux pumps. Here, we investigated the role of the AdeRS two component signal transduction system in regulating the AdeAB efflux system, determined whether AdeA and/or AdeB can individually confer antimicrobial resistance, and explored the interplay between pentamidine resistance and growth conditions in A. baumannii ATCC 17978. Results identified that deletion of adeRS affected resistance towards chlorhexidine and 4',6-diamidino-2-phenylindole dihydrochloride, two previously defined AdeABC substrates, and also identified an 8-fold decrease in resistance to pentamidine. Examination of ΔadeA, ΔadeB and ΔadeAB cells augmented results seen for ΔadeRS and identified a set of dicationic AdeAB substrates. RNA-sequencing of ΔadeRS revealed transcription of 290 genes were !2-fold altered compared to the wildtype. Pentamidine shock significantly increased adeA expression in the wildtype, but decreased it in ΔadeRS, implying that AdeRS activates adeAB transcription in ATCC 17978. Investigation under multiple growth conditions, including the use of Biolog phenotypic microarrays, revealed resistance to pentamidine in ATCC 17978 and mutants could be altered by bioavailability of iron or utilization of different carbon sources. In conclusion, the results of this study provide evidence that AdeAB in ATCC 17978 can confer intrinsic resistance to a subset of dicationic compounds and in particular, resistance to pentamidine can be significantly altered depending on the growth conditions. PLOS ONE | https://doi.org/10.1371/journal.pone

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Section: Discussionsupporting

confidence: 63%

Resistance to pentamidine is mediated by AdeAB, regulated by AdeRS, and influenced by growth conditions inAcinetobacter baumanniiATCC 17978

Adams

Stroeher

Hassan

et al. 2018

Preprint

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“…Briefly, a kanamycin resistance cassette was first amplified from the pC2HP vector [42] and cloned into the E. coli / Acinetobacter shuttle vector pWH1266 [43,44] (Additional file 5: Figure S5A and S5B). Subsequently, the baeR DNA fragment was cloned into the Xba I/ Xho I restriction sites (Additional file 5: Figure S5C).…”

Section: Methodsmentioning

confidence: 99%

Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility

Lin

Yeh

et al. 2014

BMC Microbiol

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BackgroundTigecycline resistance in Acinetobacter baumannii is primarily acquired through overexpression of the AdeABC efflux pump. Besides AdeRS, other two-component regulatory systems (TCSs) involving the regulation of this transporter have not been clarified.ResultsIn this study, we found that the TCS genes baeR and baeS are co-transcribed and function as stress responders under high osmotic conditions. The baeSR and adeAB genes showed increased transcription in both the laboratory-induced and clinical tigecycline-resistant strains compared with the wild-type strain. The deletion of baeR in the ATCC 17978 strain led to 67–73% and 68% reduction in adeA and adeB expression, respectively, with a resultant 2-fold decrease in the tigecycline minimal inhibition concentration (MIC). In contrast, the overexpression of baeR resulted in a doubled tigecycline MIC, with a more than 2-fold increase in adeA and adeB expression. The influence of baeR knockout on adeAB gene expression can also be observed in the laboratory-induced tigecycline-resistant strain. A time-kill assay showed that the baeR deletion mutant showed an approximate 1-log10 reduction in colony forming units (CFUs) relative to the wild-type strain when the tigecycline concentration was 0.25 μg/mL throughout the assay period. The wild-type phenotype could be restored by trans-complementation with pWH1266-kan r -baeR. Increasing the tigecycline concentration to 0.5 μg/mL produced an even more marked 4.7-log10 reduction in CFUs of the baeR deletion mutant at 8 h, while only a 2.1-log10 reduction was observed for the wild-type strain.ConclusionsTaken together, these data show for the first time that the BaeSR TCS influences the tigecycline susceptibility of A. baumannii through the positive regulation of the resistance-nodulation-division efflux pump genes adeA and adeB.

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“…bfmR is a gene essential for growth in human ascites, which is an ex vivo medium that reflects the infection environment (Umland et al, 2012), and is important for persistence in the lung in a murine pneumonia model (Wang et al, 2014). BfmS is also a virulence factor that plays an important role in biofilm formation, adherence to eukaryotic cells, and resistance to human serum (Liou et al, 2014). On report showed BfmR-mediated resistance to complement-mediated bactericidal activity and resistance to the clinically important antimicrobials (meropenem and colistin; Russo et al, 2016).…”

Section: Acinetobacter Baumannii Virulence Factors and Pathogenesismentioning

confidence: 99%

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

Lee

Park

et al. 2017

Front. Cell. Infect. Microbiol.

751

585

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Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized.

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The sensor kinase BfmS mediates virulence in Acinetobacter baumannii

Abstract: This study is the first to demonstrate that the pathway regulated by the sensor kinase BfmS is associated with biofilm formation, adherence to biotic surfaces, serum resistance, and antibiotic susceptibility, which may be associated with the release of Omps in A. baumannii.

Cited by 92 publications

References 24 publications

Resistance to pentamidine is mediated by AdeAB, regulated by AdeRS, and influenced by growth conditions inAcinetobacter baumanniiATCC 17978

Resistance to pentamidine is mediated by AdeAB, regulated by AdeRS, and influenced by growth conditions inAcinetobacter baumanniiATCC 17978

Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

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