Monooxygenases and Antibiotic Resistance: A Focus on Carbapenems

SIMPLE SUMMARY: Antibiotics are medicines used to prevent and treat infections in humans, animals, and plants. Antibiotic resistance is a naturally occurring phenomenon that has emerged as one of the most significant threats to global health and food security. Bacteria have the ability to acquire mutations that render them resistant to antibiotic molecules, contributing to the spread of resistance. The misuse and overuse of antibiotics have played a pivotal role in driving the development and proliferation of antibiotic resistance. The United Nations is estimating that by 2050, up to 10 million human deaths each year will be caused by the “superbugs”, very dangerous pathogens resistant to multiple antibiotic molecules. There will be health and macroeconomic consequences for the world if antimicrobial resistance is not tackled. The availability of antibiotics without prescription contributes to their overuse and misuse. Urgent measures are required to mitigate these issues and their substantial global impact. One of these measures is the search for new antibiotics designed on the basis of new targets of resistance. In this review, we show that enzymes called flavin monooxygenases could be a new and so-far-underseen candidate. ABSTRACT: Carbapenems are a group of broad-spectrum beta-lactam antibiotics that in many cases are the last effective defense against infections caused by multidrug-resistant bacteria, such as some strains of Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. Resistance to carbapenems has emerged and is beginning to spread, becoming an ongoing public-health problem of global dimensions, causing serious outbreaks, and dramatically limiting treatment options. This paper reviews the role of flavin monooxygenases in antibiotic resistance, with a specific focus on carbapenem resistance and the recently discovered mechanism mediated by Baeyer–Villiger monooxygenases. Flavin monooxygenases are enzymes involved in the metabolism and detoxification of compounds, including antibiotics. Understanding their role in antibiotic resistance is crucial. Carbapenems are powerful antibiotics used to treat severe infections caused by multidrug-resistant bacteria. However, the rise of carbapenem-resistant strains poses a significant challenge. This paper explores the mechanisms by which flavin monooxygenases confer resistance to carbapenems, examining molecular pathways and genetic factors. Additionally, this paper highlights the discovery of Baeyer–Villiger monooxygenases’ involvement in antibiotic resistance. These enzymes catalyze the insertion of oxygen atoms into specific chemical bonds. Recent studies have revealed their unexpected role in promoting carbapenem resistance. Through a comprehensive analysis of the literature, this paper contributes to the understanding of the interplay between flavin monooxygenases, carbapenem resistance, and Baeyer–Villiger monooxygenases. By exploring these mechanisms, it aims to inform the development of strategies to combat antibiotic resistance, a critical global health concern.