The StkSR Two-Component System Influences Colistin Resistance in .

is an opportunistic human pathogen responsible for numerous severe nosocomial infections. Genome analysis on the 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 response regulator was deleted via homologous recombination and its progeny, Δ, was phenotypically characterized. Antibiogram analyses of Δ 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 and wildtype cells ruled out the complete loss of lipooligosaccharide as the mechanism of colistin resistance identified for Δ. Hydrophobicity analysis identified a phenotypical change of the bacterial cells when exposed to colistin. Transcriptional profiling revealed a significant up-regulation of the operon in Δ 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.