Colistin and tigecycline resistance in carbapenemase‐producing Gram‐negative bacteria: emerging resistance mechanisms and detection methods

A literature review was undertaken to ascertain the molecular basis for tigecycline and colistin resistance mechanisms and the experimental basis for the detection and delineation of this resistance particularly in carbapenemase‐producing Gram‐negative bacteria. Pubmed, Google Scholar and Science Direct were searched with the keywords colistin, tigecycline, resistance mechanisms and detection methods. Trans‐complementation and comparative MIC studies, mass spectrometry, chromatography, spectrofluorometry, PCR, qRT‐PCR and whole genome sequencing (WGS) were commonly used to determine tigecycline and colistin resistance mechanisms, specifically modifications in the structural and regulatory efflux (acrAB, OqxAB, kpgABC adeABC‐FGH‐IJK, mexAB‐XY‐oprJM and soxS, rarA robA, ramRAB marRABC, adeLRS, mexRZ and nfxb) and lipid A (pmrHFIJFKLM, lpxA, lpxC lpxD and mgrB, pmrAB, phoPQ,) genes respectively. Mutations in the ribosomal 16S rRNA operon rrnBC, also yielded resistance to tigecycline through target site modifications. The mcr‐1 gene conferring resistance to colistin was identified via WGS, trans‐complementation and a murine thigh infection model studies. Common detection methods are mainly antibiotic sensitivity testing with broth microdilution while molecular identification tools are mostly PCR and WGS. Spectrofluorometry, MALDI‐TOF MS, micro‐array and real‐time multiplex PCR hold much promise for the future as new detection tools.