{'fraction_non_alphanumeric': 0.017969735182849937, 'fraction_numerical': 0.0069356872635561164, 'mean_word_length': 5.515400410677618, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Introduction to Antimicrobial Therapeutics Reviews: The bacterial cell wall as an antimicrobial target

Bacterial cell walls are unique structures that serve as ideal targets for antimicrobial drugs. Agents that interfere with bacterial cell wall biosynthesis or cell integrity have been used therapeutically with high efficacy and good safety since the 1940s.1,2 Because there is no comparable structure in mammalians, bacterial cell wall inhibitors can exhibit high target specificity with side effect profiles that are not target related, unlike some other classes of antibiotics. In addition, cell wall– active agents are frequently bactericidal in their action, providing the opportunity for complete bacterial clearance in serious infections. Antibiotics that target the cell wall generally have their origins in natural products, many from soil isolates that have produced commercially successful antibiotics or closely related analogs. Among these are the penicillins, cephalosporins, carbapenems, and monobactams from the -lactam class, and the cationic peptides in the naturally occurring polymyxin family, agents that are among our last hopes for treatment of infections caused by many multidrug-resistant Gram-negative bacteria. Glycopeptides and other large macrocylic natural products, such as vancomycin and daptomycin, are enjoying widespread use following the global dissemination of methicillin-resistant staphylococci beginning in the 1990s. However, it is becoming clear that we need to look beyond natural products for our next generation of antibacterial drugs. Although cell wall–active agents targeting the bacterial wall are among the mainstays of our antibacterial armamentarium, resistance to these agents, and all antibiotics, has increased at a dramatic rate, such that some have even proposed that we may be approaching an “era of untreatable infections.”3 Therefore, new approaches to antibacterial agents are urgently needed. Because of the success of agents that interact with cell wall targets, it is logical to examine the role of the cell wall, and the mechanism of action of cell wall–active agents, to evaluate the potential for novel agents in these areas. In this Annals volume, the contributors explore the various roles of the bacterial cell wall as related to the physiology of bacteria and to the development of antibacterial drugs. To set the stage for the volume, Master et al.4 provide surveillance data in the first article, demonstrating the levels of resistance in key pathogens over the period of 2007–2011. Although resistance has remained somewhat flat for some drug–bug combinations during this time, the levels of resistance to cell wall–active agents are sufficiently high to cause great concern for the utility of some of these agents. Egan and Vollmer then provide an updated review on the physiology of cell wall division5 as background to later discussions about mechanisms of action and mechanisms of resistance of various cell wall–active agents. Silver then provides a comprehensive analysis of the various screening targets related to peptidoglycan biosynthesis,6 with an emphasis on those targets that still