Protein kinase PknB as a promising target for the development of antibacterial drugs toward Staphylococcus aureus

Abstract

Antibiotic resistance is one of the biggest challenges in modern medicine. Uncontrolled use of antibiotics has led to the emergence of multidrug and extensively drug-resistant bacterial strains which are non-susceptible to almost all currently known antimicrobial drugs. Unfortunately, only a few novel antibacterial drugs have been developed in recent decades. Approximately 30% of the human population is colonized by Staphylococcus aureus. Unfortunately, the treatment of staphylococcal infections is complicated due to the ability of S. aureus to produce antibiotic-neutralizing enzymes. Today, methicillin-(MRSA) and vancomycin-resistant (VRSA) S. aureus strains are very widespread in the world and become serious medical and public problem. For example, in 2019, more than 1 million people died from infections caused by antibiotic-resistant S. aureus. Therefore, the search of novel antistaphylococcal agents with unexploited mechanisms of action is of urgent need. The serine/threonine protein kinase PknB is involved in a number of important signaling pathways of S. aureus, such as cell wall metabolism, antibiotic susceptibility, and virulence regulation. Taking into account that protein kinase PknB is a key component of the bacterial cell signaling network involved in a number of important biological processes, this enzyme can be considered as a promising molecular target for the search of novel inhibitors as antibacterial agents [7]. In this review we analyzed the current data on the structure, mechanisms of PknB activity regulation and functions, and also summarized the results of inhibitors search