penicillin
Penicillin is the original beta-lactam antibiotic, famously discovered by Alexander Fleming in 1928 when a stray mould contaminated a bacterial culture and cleared a halo around itself. It works by attacking how bacteria build their cell wall, causing the growing cell to fall apart. It launched the antibiotic era and remains a cornerstone drug almost a century later.
Penicillin binds to penicillin-binding proteins and blocks the final cross-linking step of peptidoglycan synthesis, so newly forming bacterial cell wall cannot hold together. Because the effect requires actively growing bacteria, penicillin is bactericidal against dividing cells. The family includes narrow-spectrum agents like benzylpenicillin (penicillin G), acid-stable oral forms like phenoxymethylpenicillin, and broader-spectrum members such as amoxicillin.
Two practical limitations stand out. Many bacteria now produce beta-lactamases that destroy penicillin, narrowing its usefulness, and penicillin is among the most common causes of true drug allergy. Despite this, penicillin G remains first-line for several infections, including syphilis and many streptococcal diseases, where resistance has stayed low.
Confirmed syphilis is still treated with intramuscular benzathine penicillin G, because Treponema pallidum has never developed meaningful resistance to it.
Some old drugs endure because the target organism never learned to resist them.
Penicillin G is rapidly cleared by the kidneys; historically, the drug probenecid was co-administered to block its tubular secretion and prolong its action when supplies were scarce.