A Molecular Perspective on Colistin and Klebsiella pneumoniae: Mode of Action, Resistance Genetics, and Phenotypic Susceptibility
Open Access
- 24 June 2021
- journal article
- review article
- Published by MDPI AG in Diagnostics
- Vol. 11 (7), 1165
- https://doi.org/10.3390/diagnostics11071165
Abstract
Klebsiella pneumoniae is a rod-shaped, encapsulated, Gram-negative bacteria associated with multiple nosocomial infections. Multidrug-resistant (MDR) K. pneumoniae strains have been increasing and the therapeutic options are increasingly limited. Colistin is a long-used, polycationic, heptapeptide that has regained attention due to its activity against Gram-negative bacteria, including the MDR K. pneumoniae strains. However, this antibiotic has a complex mode of action that is still under research along with numerous side-effects. The acquisition of colistin resistance is mainly associated with alteration of lipid A net charge through the addition of cationic groups synthesized by the gene products of a multi-genic regulatory network. Besides mutations in these chromosomal genes, colistin resistance can also be achieved through the acquisition of plasmid-encoded genes. Nevertheless, the diversity of molecular markers for colistin resistance along with some adverse colistin properties compromises the reliability of colistin-resistance monitorization methods. The present review is focused on the colistin action and molecular resistance mechanisms, along with specific limitations on drug susceptibility testing for K. pneumoniae.Funding Information
- Fundação para a Ciência e a Tecnologia (UID/DTP/04138/2019, CEECIND/00394/2017)
This publication has 110 references indexed in Scilit:
- Analysis of the Networks Controlling the Antimicrobial-Peptide-Dependent Induction of Klebsiella pneumoniae Virulence FactorsInfection and Immunity, 2011
- Genetic regulation of the ramA locus and its expression in clinical isolates of Klebsiella pneumoniaeInternational Journal of Antimicrobial Agents, 2011
- Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in Klebsiella pneumoniae CG43Journal of Biomedical Science, 2010
- Hepatic zonation of carbon and nitrogen fluxes derived from glutamine and ammonia transformationsJournal of Biomedical Science, 2010
- Feedback Inhibition in the PhoQ/PhoP Signaling System by a Membrane PeptidePLoS Genetics, 2009
- Structure−Activity Relationships of Polymyxin AntibioticsJournal of Medicinal Chemistry, 2009
- Involvement of pmrAB and phoPQ in Polymyxin B Adaptation and Inducible Resistance in Non-Cystic Fibrosis Clinical Isolates of Pseudomonas aeruginosaAntimicrobial Agents and Chemotherapy, 2009
- Colistin Heteroresistance in Acinetobacter and Its Association with Previous Colistin TherapyAntimicrobial Agents and Chemotherapy, 2008
- Susceptibility of Acinetobacter Strains Isolated from Deployed U.S. Military PersonnelAntimicrobial Agents and Chemotherapy, 2007
- Heteroresistance to Colistin in Multidrug-Resistant Acinetobacter baumanniiAntimicrobial Agents and Chemotherapy, 2006