Antimicrobial resistance (AMR) is a natural phenomenon in bacteria which becomes a threat for health-care settings around the world. A concerted global response is needed to tackle rising rates of antibiotic resistance, without it we risk returning to the pre antibiotic era. As bacteria evolve very fast according to the environment in which they inhabit via developing different defence mechanisms to combat with the noxious agents like different classes of antibiotics including carbapenems. This results into treatment failure and clinical complications. Global emergence of antibiotic resistance due to bacterial multidrug efflux pump systems are a major and common mechanism of intrinsic antimicrobial resistance employed by bacteria which are spreading rapidly due to over use or misuse of antimicrobial agents. This review mainly focusses on the transcriptional expression of efflux pump system AcrAB-TolC, local regulatory genes (AcrR and AcrS), mediating carbapenem resistance in clinical isolates of Escherichia coli under antibiotic stress, a genetic interplay study between intrinsic and acquired antibiotic resistance mechanisms along with a brief summary on high risk factors and prevalence of urinary tract infections by multidrug resistant Uropathogenic Escherichia coli.
- Escherichia coli
- uropathogenic Escherichia coli
Distribution of multi-drug resistant bacteria is a chief public health issue. Mutations have been an important factor influencing the development of the multi-drug resistant phenotypes and elucidate how they acquire antibiotic resistance [1, 2]. Several mutations are often required to acquire resistance towards a particular drug [3, 4]. However, a number of mechanisms evolved within bacteria helps them to survive against any noxious agents. Amongst the possible antibiotic resistance mechanisms, efflux pumps are membrane proteins which export noxious substances including antimicrobials out of the cell via over expressing the tripartite pump system resulting into antibiotic resistance . Efflux pumps (like, AcrAB-TolC in
New Delhi metallo beta-lactamase (NDM) is the predominant carbapenem resistance determinant in India which is harboured within members of enterobacteriaceae family and non-fermenters , and different variants have been reported from this country. Carbapenem resistance is a complex phenomenon which involves interplay between multiple acquired and intrinsic resistance mechanisms which includes loss or downregulation of porins, overexpression of different efflux pump systems and plasmid mediated acquirement of carbapenemase genes . A previous study has noticed that efflux pump system plays an important role in carbapenem resistance compared to blaNDM-1 in
Further, the active participation of
However, a study done by Linsenmeyer et al. demonstrated a high level of indefinite empiric treatment for urinary tract infections caused by MDR gram-negative bacteria and patients suffering from MDR UTI is treated with an inactive antimicrobial agent as their preliminary therapy . As in the previous study, estimation of non-fluoroquinolone antibiotics demonstrated the enhancement in accuracy of empiric therapy, considered as key concepts for stewardship programs . Though, based upon the severity of illness, other patient factors and favoured means of drug administration, the therapeutic options can be selected. However, the high usage of fluoroquinolone is disturbing with the emergence of high resistance rates [27, 28, 29].
Antimicrobial resistance is an intricate issue which requires a combined multi-sectoral approach. One health approach brings together various divisions and stakeholders involved in human, aquatic and terrestrial animals and plants health, feed and food production and the environment to interact and work together for designing and execution of programmes and research to accomplish improved public health outcomes. The research and development of novel antimicrobials, vaccines and rapid diagnostic tools especially for targeting dangerous gram-negative bacteria like carbapenem resistant Enterobacteriaceae requires greater innovations and investments .
Multidrug efflux pumps are primeval elements encoded in the microorganism’s chromosomes which confer resistance to antibiotics at different levels: intrinsic resistance, acquired resistance, and transient induced phenotypic resistance. Additionally, multidrug efflux pumps exhibit various functions with relevance to bacterial adaptation to altered habitats. Some of these functions, like resistance to heavy metals, resemble antibiotic resistance, biocides, or solvents, as they are adaptive responses to diverse types of external injuries, whereas, others are associated to internal detoxification of intermediate toxic bacterial metabolites. AcrAB pump is an important antibiotic resistance determinant in bacterial pathogen, having a dynamic role in developing resistance towards carbapenem group of antibiotics and the role of regulatory genes in inducing the expression of these pumps highlights the fact that the regulators directly or indirectly involved in increasing the expression of efflux pump system leading towards the development of carbapenem resistant MDR
The authors would like to acknowledge Rajiv Gandhi South Campus, Banaras Hindu University for providing favourable environment and infrastructure facilities.
Conflict of interest
|CRE||carbapenem resistant Enterobacteriaceae|
|UTIs||Urinary tract infections|
|MRSA||methicillin-resistant Staphylococcus aureus|
|UPEC||Uropathogenic Escherichia coli|
|NDM||New Delhi metallo beta-lactamase|