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Published on: January 5, 2024
Mobilization of Carbapenemase-Mediated Resistance in Enterobacteriaceae
Amy Mathers1,2
1Division of Infectious Diseases and International Health, Department of Medicine.
Abstract:
There has been a dramatic increase in the last decade in the number of carbapenem-resistant Enterobacteriaceae, often leaving patients and their providers with few treatment options and resultant poor outcomes when an infection develops. The majority of the carbapenem resistance is mediated by bacterial acquisition of one of three carbapenemases (Klebsiella pneumoniae carbapenemase [KPC], oxacillinase-48-like [OXA-48], and the New Delhi metallo-β-lactamase [NDM]). Each of these enzymes has a unique global epidemiology and microbiology. The genes which encode the most globally widespread carbapenemases are typically carried on mobile pieces of DNA which can be freely exchanged between bacterial strains and species via horizontal gene transfer. Unfortunately, most of the antimicrobial surveillance systems target specific strains or species and therefore are not well equipped for examining genes of drug resistance. Examination of not only the carbapenemase gene itself but also the genetic context which can predispose a gene to mobilize within a diversity of species and environments will likely be central to understanding the factors contributing to the global dissemination of carbapenem resistance. Using the three most prevalent carbapenemase genes as examples, this chapter highlights the potential impact the associated genetic mobile elements have on the epidemiology and microbiology for each carbapenemase. Understanding how a carbapenemase gene mobilizes through a bacterial population will be critical for detection methods and ultimately inform infection control practices. Understanding gene mobilization and tracking will require novel approaches to surveillance, which will be required to slow the spread of this emerging resistance.
Insights
Carbapenem-resistant Enterobacteriaceae infections are rising, with resistance often due to carbapenemase genes on mobile DNA. Understanding gene mobilization is key to tracking and controlling this spread.
Area of Science:
- Microbiology
- Genetics
- Epidemiology
Background:
- Carbapenem-resistant Enterobacteriaceae (CRE) infections have surged, posing significant treatment challenges due to limited therapeutic options.
- Carbapenem resistance is primarily mediated by three key carbapenemase enzymes: Klebsiella pneumoniae carbapenemase (KPC), oxacillinase-48-like (OXA-48), and New Delhi metallo-β-lactamase (NDM).
- These carbapenemase genes are frequently located on mobile genetic elements, facilitating their rapid spread through horizontal gene transfer across bacterial populations.
Purpose of the Study:
- To examine the role of mobile genetic elements in the global dissemination of carbapenemase genes.
- To highlight the impact of genetic context on the epidemiology and microbiology of KPC, OXA-48, and NDM carbapenemases.
- To emphasize the need for novel surveillance approaches focusing on gene mobilization for effective infection control.
Main Methods:
- Analysis of the genetic context surrounding prevalent carbapenemase genes (KPC, OXA-48, NDM).
- Review of global epidemiology and microbiology associated with these carbapenemases.
- Examination of horizontal gene transfer mechanisms contributing to resistance spread.
Main Results:
- Carbapenemase genes are predominantly carried on mobile DNA, enabling inter-species exchange.
- The genetic elements associated with carbapenemase genes significantly influence their spread and prevalence.
- Current antimicrobial surveillance systems are often inadequate for tracking mobile resistance genes.
Conclusions:
- Understanding carbapenemase gene mobilization is crucial for developing effective detection methods.
- Novel surveillance strategies focusing on gene mobility are essential to combat the rising threat of CRE.
- Informed infection control practices depend on a comprehensive understanding of carbapenemase gene dissemination.
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