antibiotics

antibiotics have come to be regarded in the minds of most people as substances used to combat infection. In fact they are both more and less than that; more because they are increasingly important in the chemotherapy of cancer, and less because not all drugs used to treat microbial infections are actually antibiotics. Antibiotics are substances of natural origin, and their name derives from the ecological relationship between the organism which produces them and the microbe or living tissue whose growth is inhibited by them: antibiosis — the exact antithesis of symbiosis (living together for mutual benefit). Antibiosis as a biological phenomenon was known in the nineteenth century, but the scientific term ‘antibiotic’ was only coined much later, after the young physician Alexander Fleming (later Sir Alexander) had made his seminal observations which led to the discovery of penicillin and ushered in the era of modern chemotherapy. As the story goes, in 1929 Fleming was working at St Mary's Hospital in Paddington with cultures of pathogenic bacteria (staphylococci), when one day there blew in through the partially open window of his laboratory above Praed Street a fungal spore, which landed on one of his agar plates and grew up to produce a large clump of the mould. For an ordinary microbiologist this could have been regarded as a minor inconvenience, the sort of contamination which happens from time to time if one is not super-meticulous about sterile precautions, and calls for nothing more demanding than the disposal of the contaminated plate and inoculation of a fresh one. To his credit, Fleming noticed that not only was the growth of the bacteria inhibited in the vicinity of the mould, but the colonies of staphylococci were actually disappearing or lysing. He showed that the effect was due to a substance secreted by the mould, and attempted to purify it — but it proved unstable.

It took the outbreak of World War II to galvanize the scientific community into action and exploit the discovery of penicillin for widespread clinical benefit. The problems of producing the material on an industrial scale were solved, and for the first time many infectious diseases were brought under effective control. But not all. In general, infections caused by ‘Gram positive’ bacteria (categorized by Gram's staining process) proved curable by penicillin, but treatment of those caused by ‘Gram negative’ organisms (such as dysentery, cholera, and the like) had to await the discovery of other antibiotics by screening methods which are still largely in use today. Streptomycin, tetracyclines, and numerous macrolide (‘large-ring’) antibiotics were found whose activities complemented those of penicillin. In parallel with screening approaches the chemists succeeded in creating a whole family of semi-synthetic derivatives of penicillin (generically known as β-lactam antibiotics, because they all contain the essential 4-membered β-lactam ring). These semi-synthetic drugs have extended the antibacterial spectrum of ‘natural’ penicillin, and have helped to counter the emergence of antibiotic-resistant strains of pathogenic bacteria.

Antibiotics work by selectively inhibiting processes which are peculiar to microbial cells, often ones associated with a unique structural feature, enzyme, or organelle not present in human cells. A prime example is the bacterial cell wall, the composition of which is unique in several respects. Penicillins are selectively toxic because they mimic a particular dipeptide sequence present in cell wall precursors. This molecular mimicry inactivates a crucial enzyme needed to form cross-links between the peptidoglycan chains which impart mechanical strength to the bacterial cell wall. Other antibiotics prevent protein synthesis in the bacterial cell, or inactivate enzymes concerned with the complicated processes of nucleotide and nucleic acid biosynthesis.

M. J. Waring

See also chemotherapy; infection.