Colistin Resistance Among Multiple Sequence Types of Is Associated With Diverse Resistance Mechanisms: A Report From India.

The resistance to colistin and carbapenems in infections have been associated with increased morbidity and mortality worldwide. A retrospective observational study was conducted to determine the prevalence and molecular events contributing to colistin resistance. Clinical samples were screened for colistin resistance and underlying mechanisms were studied by PCR-based amplification and sequence analysis of genes of two-component regulatory system ( and ), regulatory transmembrane protein-coding , and mobilized colistin resistance genes (). Gene expression of and was analyzed by qRT-PCR, and the genetic relationship was assessed by MLST. The putative effect of amino-acid substitutions was predicted by a combination of bioinformatics tools. Of 335 spp. screened, 11 (3.2%) were identified as colistin-resistant (MIC range, 8 to >128 μg/ml). isolates belonged to clonal complex-11 (CC11) with sequence types (STs): 14, 16, 43, 54, 147 and 395, whereby four isolates conferred three novel STs (3986, 3987 and 3988) profiles. Sequence analysis revealed non-synonymous potentially deleterious mutations in (T151A), (del87-90, del263-264, L30Q, and A351D), (G53S), (D150V, T157P, L237R, G250C, A252G, R315P, and Q331H), and (C28G) genes. The gene in three strains was disrupted by insertion sequences encoding IS-like and IS/IS family-like transposase genes. All 11 isolates showed an elevation in the transcription level of gene. Mobilized colistin-resistance () genes were not detected. All but one of the colistin-resistant isolates was also resistant to carbapenems; β-lactamase genes , , and were detected in eight, five, and nine isolates, respectively. All the studied colistin- and carbapenem-resistant isolates were genetically distinct, and various mechanisms of colistin resistance were detected, indicating its spontaneous emergence in this bacterial species.