Zuzanna Głowacka-Grzyb

The widespread emergence of multidrug-resistant pathogenic bacteria across various environments, healthcare settings, and food industries, combined with the development of new methods to combat them, highlights the need for more precise, rapid, and cost-effective pathogen detection techniques. This is especially important for clinically relevant pathogens, as it allows treatment to begin as quickly as possible, enables more effective targeted therapies to be chosen, helps preserve the effectiveness of current antibacterial agents, and prevents infections from water- and foodborne bacterial pathogens. Currently, many methods can accurately identify bacteria at the species or strain level and determine their antibiotic resistance. However, most of these techniques require sample preparation and cell culture beforehand, which can be time-consuming and labor-intensive. This review aims to highlight approaches that focus on identifying bacterial cells—especially pathogenic groups—based on their surface properties. This includes agents such as antibodies, whole phage particles, phage receptor binding proteins, cell wall-binding domains of peptidoglycan hydrolases, and functionalized magnetic nanoparticles. These agents can bind to and recognize peptidoglycan, parts of it, and other cell wall components. Developing detection kits based on these agents could enable the rapid detection of pathogenic bacteria from genera such as Acinetobacter , Bacillus , Campylobacter , Clostridium , Enterococcus , Klebsiella , Listeria , Pseudomonas , Salmonella , Shigella , Staphylococcus , Streptococcus , Vibrio , and Yersinia . These methods also offer the potential to distinguish these infectious pathogens from each other and from bacteria of the natural microbiota. Detection typically takes from a few minutes to several hours, with a broad detection range depending on the pathogen species, the detecting agent, and the technique used.

The cell wall is an indispensable element of bacterial cells and a long-known target of many antibiotics. Penicillin, the first discovered beta-lactam antibiotic inhibiting the synthesis of cell walls, was successfully used to cure many bacterial infections. Unfortunately, pathogens eventually developed resistance to it. This started an arms race, and while novel beta-lactams, either natural or (semi)synthetic, were discovered, soon upon their application, bacteria were developing resistance. Currently, we are facing the threat of losing the race since more and more multidrug-resistant (MDR) pathogens are emerging. Therefore, there is an urgent need for developing novel approaches to combat MDR bacteria. The cell wall is a reasonable candidate for a target as it differentiates not only bacterial and human cells but also has a specific composition unique to various groups of bacteria. This ensures the safety and specificity of novel antibacterial agents that target this structure. Due to the shortage of low-molecular-weight candidates for novel antibiotics, attention was focused on peptides and proteins that possess antibacterial activity. Here, we describe proteinaceous agents of various origins that target bacterial cell wall, including bacteriocins and phage and bacterial lysins, as alternatives to classic antibiotic candidates for antimicrobial drugs. Moreover, advancements in protein chemistry and engineering currently allow for the production of stable, specific, and effective drugs. Finally, we introduce the concept of selective targeting of dangerous pathogens, exemplified by staphylococci, by agents specifically disrupting their cell walls.