Mobile Plasmid Mediated Transition From Colistin-Sensitive to Resistant Phenotype in

Multidrug-resistant bacteria, including carbapenem-resistant (CRKP), are becoming an increasing health crisis worldwide. For CRKP, colistin is regarded as "the last treatment option." In this study, we isolated a clinical CRKP strain named as R10-341. Phenotyping analysis showed that this strain could transit from a colistin-sensitive to a resistant phenotype by inserting an IS family IS element into the colistin-resistance associated gene. To investigate the mechanism of this transition, we performed genome sequencing analysis of the colistin-sensitive parental strain and found that 12 copies of IS containing direct repeats (DR) are located on the chromosome and 1 copy without DR is located on a multidrug-resistant plasmid pR10-341_2. Both types of IS could be inserted into the gene to cause colistin-resistance, though the plasmid-derived IS without DR was in higher efficiency. Importantly, we demonstrated that colistin-sensitive strain transferred with the IS element also obtained the ability to switch from colistin-sensitive to colistin-resistant phenotype. Furthermore, we confirmed that the IS-containing pR10-341_2 plasmid was able to conjugate, suggesting that the ability of causing colistin-resistant transition is transferable through common conjugation. Our results point to new challenges for both colistin-resistance detection and CRKP treatment.