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Published on: February 1, 2018
The emergence and implications of metallo-beta-lactamases in Gram-negative bacteria
1Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol, UK. t.r.walsh@bristol.ac.uk
Abstract:
The increase in Gram-negative broad-spectrum antibiotic resistance is worrisome, particularly as there are few, if any, ''pipeline'' antimicrobial agents possessing suitable activity against Pseudomonas spp. or Acinetobacter spp. The increase in resistance will be further enhanced by the acquisition of metallo-beta-lactamase (MBL) genes that can potentially confer broad-spectrum beta-lactam resistance. These genes encode enzymes that can hydrolyse all classes of beta-lactams and the activity of which cannot be neutralised by beta-lactamase inhibitors. MBL genes are often associated with aminoglycoside resistant genes and thus bacteria that possess MBL genes are often co-resistant to aminoglycosides, further compromising therapeutic regimes. Both types of genes can be found as gene cassettes carried by integrons that in turn are embedded within transposons providing a highly ambulatory genetic element. The dissemination of MBL genes is typified by the spread of blaVIM-2, believed to originate from a Portuguese patient in 1995, and is now present in over 20 counties. The increase in international travel is likely to be a contributory factor for the ascendancy of mobile MBL genes as much as the mobility among individual bacteria. Fitness, acquisition and host dependency are key areas that need to be addressed to enhance our understanding of how antibiotic resistance spreads. There is also a pressing need for new, and hopefully novel, compounds active against pan-resistant Gram-negative bacteria--a growing problem that needs to be addressed by both government and industry.
Insights
Metallo-beta-lactamase (MBL) genes are increasing Gram-negative antibiotic resistance, complicating treatment for infections like Pseudomonas and Acinetobacter. New antimicrobial agents are urgently needed to combat these resistant bacteria.
Area of Science:
- Microbiology
- Molecular Biology
- Infectious Diseases
Background:
- Rising Gram-negative antibiotic resistance poses a significant global health threat.
- Limited new antimicrobial agents are effective against key resistant pathogens like Pseudomonas and Acinetobacter.
- Metallo-beta-lactamase (MBL) genes confer broad-spectrum resistance to beta-lactam antibiotics, which cannot be inhibited by existing drugs.
Purpose of the Study:
- To highlight the growing threat of metallo-beta-lactamase (MBL) genes in Gram-negative bacteria.
- To emphasize the co-resistance patterns associated with MBL genes and their impact on treatment options.
- To underscore the urgent need for novel antimicrobial compounds against pan-resistant Gram-negative bacteria.
Main Methods:
- Review of current literature on antibiotic resistance mechanisms, focusing on MBL genes.
- Analysis of gene mobility, dissemination pathways, and associated resistance patterns.
- Identification of knowledge gaps in understanding bacterial fitness, acquisition, and host dependency related to resistance.
Main Results:
- MBL genes, such as blaVIM-2, are rapidly disseminating globally, often linked with aminoglycoside resistance genes.
- These mobile genetic elements, including integrons and transposons, facilitate the spread of resistance.
- International travel and bacterial mobility are key factors in the global ascendancy of MBL genes.
Conclusions:
- The increasing prevalence of MBL genes and co-resistance presents a critical challenge for effective antimicrobial therapy.
- Further research into bacterial resistance mechanisms and host-pathogen interactions is essential.
- Urgent development of novel antimicrobial agents by both government and industry is required to address the growing problem of pan-resistant Gram-negative bacteria.
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