Aztreonam - The lonely monobactam from a purple bacterium

I appear to be on a bit of an obscure antibiotic kick right now, so bear with me!

In 1928, a Scotsman named Alex Fleming discovered that a mould contaminating one of his Petri plate-based bacterial cultures was dissolving the bacterial colonies around it as it grew. Fortunately for us all, he decided to play around with the mould and managed to extract an antibacterial substance that he boringly named penicillin, after the genus of mould that produced it. It was subsequently shown to be highly effective at treating bacterial infections in humans. World War II came along, spurring the development of a means of mass-production of the drug and ultimately saving the lives of a huge number of infected Allied soldiers. Penicillin went on to revolutionize the treatment of bacterial infections worldwide. The functional group in penicillin that enables it to smite bacteria is the beta-lactam ring. This ring is only four-sided, making it relatively unstable and permitting it to bind to and inactivate an enzyme necessary to make a strong bacterial cell wall. Affected bacteria with wussed-out walls are killed by the uncontrolled buildup of osmotic pressure, which generally causes them to pop/burst/rupture.

Approximately one zillion derivatives of penicillin have since been developed in an attempt to increase the range of bacteria that it can fight and improve its pharmacokinetics (essentially, its ability to get to the site of infection at a high enough concentration to do its thing) and safety. Further research in the realm of microbe-produced antibiotics has yielded a slew of other beta-lactam ring-containing classes of drugs. These include cephalosporins (original compound is produced by fungi of the genus Acremonium), cephamycins (produced by bacteria of the genus Streptomyces), cephabacins (produced by several bacteria of the family Xanthomonadaceae), carbapenems (based on thienamycin, a product of the bacterium Streptomyces cattleya), nocardicins (produced by the bacterium Nocardia uniformis), and monobactams (produced by the bacteria Chromobacterium violaceum).

The monobactams are neat because a) only one of them (aztreonam) has actually been developed into a commercially available drug and b) their beta-lactam ring is not fused to another ring, as it is in all of the other classes except the nocardicins. The natural synthesizer of aztreonam (Azactam), Chromobacterium violaceum, is a Gram-negative rod-shaped bacteria found in water and soil all over the world that occasionally infects humans. When grown in culture, it produces distinctive smooth metallic dark violet colonies, reflecting the production of a pigment called violacein, which is capable of killing amoebae and trypanosomes. C. violaceum also produces other antibiotics, including aerocyanidine and aerocavin. Unlike the penicillins, aztreonam is lousy at binding to and destroying gram-positive and anaerobic bacteria. However, it has good activity against most aerobic gram-negative bacteria, including those belonging to the genus Pseudomonas. In the clinic, aztreonam must be injected. An inhaled form has been developed (based on the use of an ultrasonic nebulizer to render a solution of the drug airborne as a mist) and is currently in trials.

- Aoki H, Sakai H, Kohsaka M, Konomi T, Hosoda J. Nocardicin A, a new monocyclic beta-lactam antibiotic. I. Discovery, isolation and characterization. J Antibiot (Tokyo). 1976 May;29(5):492-500.
- DurĂ¡n N, Menck CF. Chromobacterium violaceum: a review of pharmacological and industiral perspectives. Crit Rev Microbiol. 2001;27(3):201-22. Review.
- Hellinger WC, Brewer NS. Carbapenems and monobactams: imipenem, meropenem, and aztreonam. Mayo Clin Proc. 1999 Apr;74(4):420-34. Review.
- Ono H, Nozaki Y, Katayama N, Okazaki H. Cephabacins, new cephem antibiotics of bacterial origin. I. Discovery and taxonomy of the producing organisms and fermentation. J Antibiot (Tokyo). 1984 Dec;37(12):1528-35.

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