Abstract
Bacterial infections involving antibiotic-resistant gram-negative bacteria continue to increase and represent a major global public health concern. Resistance to antibiotics in these bacteria is mediated by chromosomal and/or acquired resistance mechanisms, these give rise to multi-drug resistant (MDR), extensive-drug resistant (XDR) or pan-drug resistant (PDR) bacterial strains. Most recently, plasmid-mediated resistance to colistin, an antibiotic that had been set apart as the last resort antibiotic in the treatment of infections involving MDR, XDR and PDR gram-negative bacteria has been reported. Plasmid-mediated colistin resistant gram-negative bacteria have been described to be PDR, implying a state devoid of alternative antibiotic therapeutic options. This review concisely describes the evolution of antibiotic resistance to plasmid-mediated colistin resistance and discusses the potential role of high-throughput sequencing technologies, genomics, and bioinformatics towards improving antibiotic resistance surveillance, the search for novel drug targets and precision antibiotic therapy focused at combating colistin resistance, and antibiotic resistance as a whole.
Highlights
In the recent past, old antibiotic classes previously deemed unfit for treatment of bacterial infections due to associated toxicity concerns have been recommended for the treatment of the same infections[1,2]
It describes the evolution of antibiotic resistance to plasmid-mediated colistin resistance and the potential role of genomics and bioinformatics in precision antibiotic therapy targeted towards combating colistin resistance and antibiotic resistance
highthroughput sequencing technology (HTS) and bioinformatics analyses have made it possible to employ comprehensive whole-genome sequencing (WGS)-based surveillance of colistin resistance and antimicrobial resistance as a whole by enabling the rapid detection of colistin resistance as well as resistance to other antibiotics; these have made it possible to map how resistance spreads in a One-Health perspective in a way that was not possible before[53,54]
Summary
University of Padova, This article is included in the Antimicrobial Resistance collection. Any reports and responses or comments on the article can be found at the end of the article. This manuscript has been revised to address the comments of the reviewers. We reworked the section on Africa and added a section that briefly describes how HTS leads to the rapid detection of the spread of the newly identified colistin resistance risk after reviewing the articles that had been suggested. We reworked the sections that had been hinted upon as being too long and, lacking clarity, precision, and completeness, we made these sections shorter, more clear, precise and, complete. We highlighted the potential of WGS in the identification of chromosomally mediated resistance mechanisms as well as acquired resistance mechanisms
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