Commentary: "The Development of an Ideal Antibiotic Compound: A Fairy Tale or a Possible Reality?"

Abstract

Original article citation: “The concept of an ideal antibiotic: implications for drug design” by Márió Gajdács. Molecules 2019, 24(5), 892; doi: 10.3390/molecules24050892 After the discovery of penicillin by Alexander Flemming in 1928, the landscape of healthcare has changed drastically, and previously lethal infections have become treatable1. However, the emergence and spread of multidrug-resistant bacteria is currently a major public health issue affecting patients, healthcare professionals, scientists, drug development companies and government officials alike2. Various bacterial resistance mechanisms have been described, allowing pathogens to evade lethal effects of antibiotics, the most important mechanisms being enzymatic degradation (e.g., β‐lactamases, aminoglycoside‐degrading enzymes), target alteration (e.g., penicillin-binding proteins, bacterial topoisomerases), decreased uptake (porin‐deficient mutants) and overexpression of energy‐dependent efflux pump proteins (e.g., AcrAB-TolC in Enterobacteriaceae)3. Multidrug‐resistant (MDR) bacteria can withstand potentially lethal doses of antibiotics with various chemical structures and mechanisms of action. The World Health Organization (WHO), the European Center for Disease Prevention and Control (ECDC), and the Centers for Disease Control and Prevention in the US (CDC) have all published reports on the significance of MDR bacteria4. All of these reports concluded that antibiotic resistance is a global issue that may become the major cause of mortality by 2050. So‐called “ESKAPE” bacteria have been described as the most important problem, including E: Enterococcus faecium, S: Staphylococcus aureus or recently Stenotrophomonas maltophilia, K: Klebsiella pneumoniae or recently C: Clostridioides difficile, A: Acinetobacter baumannii, P: Pseudomonas aeruginosa, E: Enterobacter spp., or recently Enterobacteriaceae5.