STUDY OF GENE EXPRESSION IN RESPONSE TO SERIAL EXPOSURE TO MEROPENEM IN BACTEROIDES FRAGILIS

Antibiotic resistance is a major global health concern, and inappropriate antibiotic use contributes significantly to the development of resistance in pathogens. Bacteroides fragilis, an anaerobic bacterium, is commonly treated with β-lactam antibiotics like meropenem. B. fragilis possesses various antibiotic resistance mechanisms, including enzymatic modification of antibiotics, efflux systems, and reduction of cell membrane permeability. The primary mechanism of carbapenem resistance in B. fragilis is linked to the production of a metallo-β-lactamase encoded by the cfiA gene. However, this gene is frequently inactive and requires activation by insertion elements. The study aimed to explore the expression of specific genes in B. fragilis associated with different metabolic pathways in response to exposure to sub-inhibitory concentrations of meropenem. The study used B. fragilis strain BFR KZ01, obtained from a patient with appendicitis and peritonitis. Serial exposure to meropenem was conducted, and gene expression was analyzed using quantitative RT-PCR. Significant and long-lasting alterations in gene expression patterns were observed in B. fragilis following exposure to meropenem, even after removal of the antibiotic. Genes such as cfiA, oxyR, and Ddl showed heightened expression levels even after discontinuation of meropenem. The study discussed the implications of gene expression changes induced by meropenem exposure, highlighting the role of oxidative stress response (oxyR), D-Ala-D-Ala ligase (Ddl), and carbapenemase (cfiA) genes in antibiotic resistance mechanisms. The study concluded that exposure to meropenem induced lasting alterations in gene expression in B. fragilis, contributing to antibiotic resistance. Understanding these mechanisms is crucial for developing strategies to combat antibiotic resistance.