Molecular mechanisms of resistance of Bacteroides fragilis bacteria to carbapenem

Abstract

Carbapenems are generally the most successful group of antibacterial drugs due to the combination of a wide spectrum of activity, rapid bactericidal effect, greater potential for the selection of resistant strains and resistance compared to other classes of antibacterial drugs. Carbapenems are potent antimicrobial agents that effective against a wide range of bacteria, including both gram-positive and gram-negative types. Bacteroides fragilis is one of the important and frequently isolated bacteria in clinical laboratories for mono- and polymicrobial infections. Bacteroides fragilis is also resistant to macrolides, beta-lactams, metronidazole, and some newer fluoroquinolones. Carbapenem resistance is considered a rapidly growing problem due to overuse of the drug in therapy. Molecular mechanisms of carbapenem resistance in bacteria involve several factors. The first mechanism is associated with the development of multidrug resistance in microorganisms through the export of drugs via efflux systems. This process enables bacteria to avoid the negative effects of antibiotics. The second mechanism involves the synthesis of beta-lactamases, which is a key factor in the resistance of Bacteroides fragilis to beta-lactam compounds, including carbapenems. These enzymes are capable of hydrolyzing the beta-lactam ring of antibiotics, rendering them inactive. The third mechanism involves changes in the structure of penicillin-binding proteins (PBPs), which are the target sites for carbapenems. Mutations in genes encoding PBPs can lead to decreased affinity of carbapenems to these proteins, making them less sensitive to the antibiotic. The cfiA gene plays an important role in carbapenem resistance, especially in B. fragilis. It encodes a protein that confers resistance to carbapenems and other beta-lactam antibiotics. This gene can be horizontally transferred between different bacteria, increasing the risk of resistance spreading. Understanding the mechanism of antimicrobial resistance is important to avoid pitfalls when selecting alternative antimicrobials for the treatment and prevention of severe infections. This article examines several mechanisms that influence the resistance of B. fragilis strains to carbapenems.