Innovative solutions to sticky situations: Antiadhesive strategies for treating bacterial infections

Abstract

The discovery of penicillin in 1928 and its subsequent introduction as a therapeutic in the 1940s sparked the antibiotic era, ushering in effective treatment options for many common bacterial infections (1). Following the end of World War II, several pharmaceutical companies including Bayer, Merck, and Pfizer became household names through the discovery and clinical success of a number of additional antibiotics, which were identified by screening soil samples for antimicrobial activity (1). Compounds identified during this screening became the founding members of many now-ubiquitous groups of antibiotics, including the tetracycline, rifamycin, quinolone, and aminoglycoside families. In the early 1970s, declining rates of novel antibiotic discovery from microbial sources shifted the onus of antimicrobial development to synthetic chemists, who were tasked with designing and screening new compounds based on known principles of antibiotic design. These synthetic chemists were faced with many practical challenges, including poor penetration into bacterial cells, bacterial enzymes, and/or efflux pumps that degrade or expel the compounds, respectively, innate resistance mechanisms, and the requirement of high concentrations of some compounds that result in toxic side effects (2, 3).