It may not surprise you to hear that a story which starts knee-deep in sewage will end with the spread of drug resistant infections like MRSA and c. This is the story of cephalosporins — a diverse class of structurally similar antibiotics. But back to the sewage.
As you might imagine, a sewer system is a rich microbial ecosystem, fed with human waste and plenty of water. This gives rise to interesting interactions, where many species fight amongst the faeces, vying for dominance and continually evolving new ways to stay on top. As a result, the chemical mechanisms developed by some of these species make ideal drug candidates.
In , Italian scientist Guiseppe Brotzu was examining fungal cultures extracted from a sewer in Sardinia. Although penicillin had been discovered 20 years earlier, it only became regularly used to treat infections in , so the idea that fungi could provide useful antibacterial drugs was still relatively new and exciting.
He noticed that cultures of the fungus Cephalosporium acremonium suppressed growth of Salmonella typhi , the infectious agent responsible for typhoid, and that a crude filtrate from the fungus could also inhibit growth of Staphylococcus aureus. In Oxford, Guy Newton and Edward Abraham, the latter best known for his contribution to the development of penicillin, took the cephalosporin story to the next chapter.
They isolated and refined compounds from the culture, removing side chains until they fell upon 7-aminocephalosporic acid, or 7-ACA — the nucleus of cephalosporins. This, much like 6-aminopenicillanic acid with penicillin, acts as the starting block for a host of derivatives, the mother to several generations of drugs. Cefalotin, the first of the cephalosporins to reach the market, was first released in , and continues to be used today.
They share a similar mode of action, inhibiting cell wall development and leading to cell disruption and lysis. First-generation cephalosporins, in common with other early drugs in their class, were only really effective against gram-positive bacteria, which include the bugs behind tetanus, anthrax and diphtheria. Later generations were modified to increase oral availability and plasma stability, as well as improve activity against gram-negative bacteria.
There are just two drugs in the fifth generation — Ceftobiprole and Ceftaroline, but they account for the only drugs of their type that are effective against methicillin-resistant-Staphylococcus-aureus MRSA.
But instead of fame and glory, cephalosporins have attracted criticism and are considered by some to be the driving force behind the development of drug-resistant bacteria. In a article in the Journal of antimicrobial chemotherapy , Stephanie Dancer of the Vale of Leven District General Hospital in Dunbartonshire examined the evidence that…. For known pathogens this obviously leads to secondary infections, but it can also alter the balance so much that low risk, or even friendly bacteria can become a problem — when allowed to overgrow, Candida albicans causes yeast infections, and Clostridium difficile , which can exist without issue in the gut for years, can become a killer.
By then, though, we may be contemplating the post-antibiotic era. So a drug that started its story in a sewer, and went on to find glory in treating and preventing infection, may be one of the causes of two major changes in the history of medicine. Now next week, things are getting complex. The B complex comprises 8 vitamins and of these, one of the better known is vitamin B 1 or thiamine.
New, sensitive screening methods have revealed further families of clinically useful substances that contain a reactive beta-lactam ring. Genetic engineering has now begun to throw light on the nature of the enzymes that are involved in the biosynthesis of penicillins and cephalosporins, and x-ray crystallography may soon provide detailed 3-dimensional pictures of some of the bacterial enzymes with which the active beta-lactam ring reacts. Rational approaches to the production and design of new and potentially useful compounds may then be within sight.
Abstract In , after penicillin had been introduced into medicine, an antibiotic-producing species of Cephalosporium was isolated from a sewage outfall in Sardinia. Publication types Historical Article Review. Substances Cephalosporins.
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