title: Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria: emerging resistance mechanisms and detection methods.
abstract: 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.
authors.affiliation: Antimicrobial Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: J
authors.identifier: http://orcid.org/0000-0002-9508-984X
authors.initials: J
authors.lastname: Osei Sekyere
authors.affiliation: Antimicrobial Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: U
authors.initials: U
authors.lastname: Govinden
authors.affiliation: Biomedical Resource Unit, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: L A
authors.initials: LA
authors.lastname: Bester
authors.affiliation: Antimicrobial Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: S Y
authors.initials: SY
authors.lastname: Essack
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003091:Colistin / Q000494:pharmacology* / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology; D006801:Humans; D008050:Lipid A / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009154:Mutation; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism; D012336:RNA, Ribosomal, 16S / Q000235:genetics / Q000378:metabolism; D000078304:Tigecycline; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008050:Lipid A; D026901:Membrane Transport Proteins; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D000078304:Tigecycline; D001618:beta-Lactamases; C063912:carbapenemase; D008911:Minocycline; D003091:Colistin
keywords: acrRAB-TolC; adeABCDFGHIJK; carbapenems; lipid A; mexAB-XY-oprJM; qRT-PCR; whole genome sequencing