Emerging Mechanisms of Antimicrobial Resistance in Bacteria and Fungi: Advances in the Era of Genomics

Abstract

Bacteria and fungi continue to develop new ways to adapt and survive the lethal or biostatic effects of antimicrobials through myriad mechanisms. Novel antibiotic resistance genes such as lsa(C), erm(44), VCC-1, mcr-1, mcr-2, mcr-3, mcr-4, bla and bla were discovered through comparative genomics and further functional studies. As well, mutations in genes that hitherto were unknown to confer resistance to antimicrobials, such as trm, PP2C, rpsJ, HSC82, FKS2 and Rv2887, were shown by genomics and transcomplementation assays to mediate antimicrobial resistance in Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecium, Saccharomyces cerevisae, Candida glabrata and Mycobacterium tuberculosis, respectively. Thus, genomics, transcriptomics and metagenomics, coupled with functional studies are the future of antimicrobial resistance research and novel drug discovery or design.

Mcr colistin resistance gene: a systematic review of current diagnostics and detection methods

“…These assays cannot confirm colistin resistance as colistin susceptible MCR‐positive strains exist (Chew et al., ). Moreover, they cannot detect unknown colistin‐resistance mechanisms due to their dependence on highly specific primers and probes; only WGS can identify unknown colistin resistance mechanisms (Osei Sekyere & Asante, ).…”

“…Conventional PCR and WGS are the gold‐standards and first diagnostic tools used in identifying the mcr‐1 gene from swine E. coli isolates (Liu et al., ; Rebelo et al., ). While conventional PCR can only detect known mcr resistance genes within a shorter period, WGS can identify all known or unknown colistin resistance mechanisms within at most 2 days depending on the WGS instrument used (Osei Sekyere & Asante, ). In addition, conventional PCR can only identify one mcr type per reaction while WGS can identify all colistin resistance mechanisms per single reaction (Osei Sekyere & Asante, ; Xavier et al., ).…”

“…While conventional PCR can only detect known mcr resistance genes within a shorter period, WGS can identify all known or unknown colistin resistance mechanisms within at most 2 days depending on the WGS instrument used (Osei Sekyere & Asante, ). In addition, conventional PCR can only identify one mcr type per reaction while WGS can identify all colistin resistance mechanisms per single reaction (Osei Sekyere & Asante, ; Xavier et al., ). To enable the multiple detection of several mcr genes and variants in a single reaction, seven studies have designed real‐time and multiplex PCR assays using either Taqman ® probes, self‐designed probes or SYBR ® Green (Tables and ).…”

“…The combined emergence of plasmid‐mediated carbapenem and colistin resistance, has thrown clinical medicine into a state of shock and therapeutic conundrum as infection control and management have become more difficult with little or no therapeutic options (Osei Sekyere, ; Osei Sekyere, & Asante, ; Osei Sekyere, Govinden, Bester, & Essack, ). Prior to the advent of carbapenem and colistin resistance in Gram‐negative bacteria, these two antibiotics were, respectively, used as last‐resort antibiotics for fatal and multidrug‐resistant infections (MDRIs) mediated by extended‐spectrum β‐lactamases (ESBLs) and carbapenemases (Osei Sekyere et al., ).…”

Plasmid evolution in carbapenemase‐producing Enterobacteriaceae: a review

“…Plasmid prediction database servers, such as Plasmidfinder, pMLST, PLACNET, and plasmidSPAdes, enable easy identification and annotation of relevant plasmid sequences from large WGS datasets, as well as assemble plasmids from WGS data . PlasmidFinder is a web‐based tool that allows the submission of raw or assembled reads, which are searched for through a plasmid replicon database to identify replicons and assign the plasmid to an Inc group .…”