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

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 recombination and its progeny, Δ stkR , was phenotypically characterized. Antibiogram analyses of Δ 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 Δ stkR and wildtype cells ruled out the complete loss of lipooligosaccharide as the mechanism of colistin resistance identified for Δ 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 Δ 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.