Carbapenemases: Partners in crime

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Carbapenemases are enzymes that confer resistance to carbapenems and other beta-lactam antibiotics.
• These enzymes are found in Gram-negative bacteria and include serine carbapenemases (e.g., KPC) and metallo-beta-lactamases (e.g., IMP, NDM, VIM).
• Carbapenemase-producing bacteria often possess multiple beta-lactamase genes and other resistance mechanisms.

Approach:

• Analysis of the molecular and biochemical characteristics of various beta-lactamases.
• Investigation of the genetic basis of antibiotic resistance in Gram-negative pathogens.
• Examination of the co-occurrence of carbapenemase genes with other resistance determinants on mobile genetic elements.

Key Points:

• Carbapenemases, including KPC, IMP, NDM, and VIM families, are key drivers of beta-lactam antibiotic resistance.
• Gram-negative bacteria frequently co-express multiple beta-lactamases and other resistance genes (e.g., aminoglycoside-modifying enzymes, 16S rRNA methylases).
• Mobile genetic elements facilitate the spread of carbapenemase genes alongside resistance determinants for fluoroquinolones, sulfonamides, and other antibiotic classes.

Conclusions:

• The proliferation of transferable carbapenemases significantly broadens antibiotic resistance across multiple drug classes.
• Multidrug-resistant bacteria are increasing, highlighting the urgent need for judicious antibiotic stewardship.
• Development of novel antibacterial agents is crucial to combat the growing threat of antibiotic resistance.