Integrons as the potential targets for combating multidrug resistance inEnterobacteriaceaeusing CRISPR- Cas9 technique

Abstract

The emergence of multi-drug resistance (MDR) to pan-drug resistance (PDR) in Enterobacteriaceae has made treatment extremely challenging. Genetic mutations and horizontal gene transfer (HGT) through mobile genetic elements (MGEs) were frequently associated mechanisms of drug resistance in pathogens. However, transposons, plasmids, and integrons transfer MDR genes in bacterium via HGT much faster. Integrons are dsDNA segment that plays a crucial role in the adaptation and evolution of bacteria. They contain multiple gene cassettes that code for antibiotic resistance determinants that are expressed by a single promoter (Pc). Integrons are the cause of drug resistance in Enterobacteriaceae. Although alternatives to antibiotics such as bacteriophages, phage proteins, antimicrobial peptides, and natural compounds have been widely used to treat MDR infections, there have been limited efforts to reverse the antibiotic resistance ability of bacteria. Thus, silencing the genes harboured on MGEs achieved by Gene Editing Techniques (GETs) might prevent the spread of MDR. One such GETs, which has a simple design, good repeatability, low cost, and high efficiency, is CRISPR- Cas9 system. Thus, this review is a first of the kind that focuses on utilizing the structure of an integron to make it an ideal target for GETs like CRISPR- Cas9 systems.

Antibiotic resistance pattern of Methicillin-resistant Staphylococcus aureus isolated from hospitalized patients

“…The recent discovery of a mechanism of linezolid resistance based on acquisition of a natural and potentially transferable resistance gene that modifies a specific rRNA nucleotide located in the site of the drug action is of particular concern and could completely change the picture of linezolid susceptibility in the future. This gene is apparently associated with mobile genetic elements which raises the possibility of its transmission both intra-species and to other pathogenic strains [23][24][25].…”

Outer Membrane Proteins and Efflux Pumps Mediated Multi-Drug Resistance in Salmonella: Rising Threat to Antimicrobial Therapy

“…and E. coli . Most common modifications are observed in gyrA83 and parC80 regions of gyrase and topoisomerase IV enzymes involved in DNA folding and unfolding. , Another important mechanism of resistance is the inactivation of antibiotics. This is the common cause of antibiotic resistance in Salmonella , where the resistance genes encode the enzyme capable of chemically modifying and inactivating the antibiotics .…”

A South African Perspective on the Microbiological and Chemical Quality of Meat: Plausible Public Health Implications

“…Horizontal gene transfer is recognised as the major cause of rapid multiplication of antibiotic resistance genes among widely diversified bacterial organisms [243]. Integrons as mobile genetic elements consist of unique backbone genes, enabling them via the process of homologous and non-homologous recombination to replicate the chromosome independently [244]. They are of a versatile structure accommodating several antibiotic resistance genes, therefore serving as a scaffold for the rearrangement of multiple genes by site-specific recombination gene cassettes.…”

“…Integrons can be differentiated based on mobility into two categories, namely, mobile integrons and super integrons. Shetty and colleagues [244] explained that mobile integrons rely on transposons or plasmids for movement and harbour antibiotic resistance genes with several attC sites but with only some gene cassettes. Sometimes, mobile integrons are known as resistant integrons or multidrug resistance integrons.…”

“…Table 3. Different classes of integrons and some of their gene cassettes expressing antibiotic resistance (adopted and modified from Sabbagh et al [241] and Shetty et al [244]).…”