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

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Abstract

Acinetobacter baumannii is an opportunistic human pathogen responsible for numerous severe nosocomial infections. Genome analysis on the A. baumannii clinical isolate 04117201 revealed the presence of 13 two-component signal transduction systems (TCS). Of these, we examined the putative TCS named here as StkSR. The stkR response regulator was deleted via homologous recom-bination and its progeny, ∆stkR, was phenotypically characterized. Antibiogram analyses of ∆stkR cells revealed a two-fold increase in resistance to the clinically relevant polymyxins, colistin and polymyxin B, compared to wildtype. PAGE-separation of silver stained purified lipooligosaccharide isolated from ∆stkR and wildtype cells ruled out the complete loss of lipooligosaccharide as the mechanism of colistin resistance identified for ∆stkR. Hydrophobicity analysis identified a phenotypical change of the bacterial cells when exposed to colistin. Transcriptional profiling revealed a significant up-regulation of the pmrCAB operon in ∆stkR compared to the parent, associating these two TCS and colistin resistance. These results reveal that there are multiple levels of regulation affecting colistin resistance; the suggested ‘cross-talk’ between the StkSR and PmrAB two-component systems highlights the complexity of these systems.

Original languageEnglish
Article number985
Number of pages17
JournalMicroorganisms
Volume10
Issue number5
DOIs
Publication statusPublished - May 2022

Keywords

  • adherence
  • antibiotic resistance
  • hydrophobicity
  • Lipid A
  • phosphoethanolamine
  • pmrCAB
  • TCS

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