(anti) Disease of the week: Antibiotics – Fighting fire with the gooey bits that come out of other fires

Surprise article from me (bailing James out, as per usual). This is another old On Dit article. Although not technically a disease, antibiotics are much closely related to pathogens than you might think. Plus, I was sick of painting an entirely bad picture of microbes.

Antibiotics have been one of the most successful ways of saving human life ever discovered. Before antibiotics, a person who accidentally cut themselves would fear infections like cancer. An infected wound could mean necrosis of a limb (requiring amputation), septicaemia, multiple organ failure or death. Today, simply taking a pill is enough to avert this.

All hail Lord Amoxycillin, Bringer of cures and Bane of broad-ranged evils! (Side effects of worshipping Amoxycillin include nausea, vomiting, rashes, diarrhea and antibiotic-associated colitis. Those allergic to beta-lactam antibiotics should consider a different Lord.) (Picture taken by Thomas Tu)

A commonly used definition of an antibiotic is “a microbial product or derivatives which kill microbial agents or inhibit their growth”, although now some antibiotics (such as chloramphenicol) can be synthesised completely in vitro. You might wonder why microbes spurt out poison chemicals. It’s a selfish thing. If a bacterium kills all the other bacteria around it, it has more sugar and other resources to grow. So, that bacterium will become more prominent and become the norm in the species. Woo, natural selection! There are over 100 antibiotics, but a lot of them are slight variations of each other and fit into several families.

Sulphonamides

Though not an antibiotic by the earlier definition (it is derived from a dye rather than a micro-organism), sulphonamides (in the form of sulpha powder) were quite an important part of preventing septic wounds in warfare. Some of you may recall, it’s the powder sprinkled on wounds in Saving Private Ryan, M*A*S*H and the like.

The story of this drug’s discovery highlights how boring research can be. In 1927 some German chemical factory told one of their researchers Gerhard Doamgk (paraphrased) “Here, here’s all these chemicals. Go see if they kill germs.” So basically, he injected every chemical that came down the line into infected mice and saw if they died (Needle goes in, needle comes out, needle goes in, needle comes out…). Through this tedious process a leather dye called Prontosil Red was discovered to have protective effects against Staphylococci and Streptococci (two very common genera of pathogens, whose effects I will probably cover in future articles). Doamgk published his results and later that year with Jacques and Therese Trefouel found the active ingredient, sulphanilamide.

Folic acid is used in bacteria and humans alike to make DNA, RNA and some essential amino acids. Sulphonamides work by screwing up folic acid production in the bacteria and thereby stopping them from reproducing. The family of drugs doesn’t kill humans because we take in folic acid from our diet rather than make it ourselves.

However, their use has been scaled down because of both the increasing resistance of bacteria to the drug and the high numbers of allergic reactions associated with it (up to 5%). Allergy to sulpha powder can lead to hives, anaemia, kidney damage and liver damage. It is also a suspected causative agent of toxic epidermal necrosis, a disorder wherein a large portion of the epidermis (can get up to >30% of total body surface area) detaches from the dermis. Patients usually die of secondary infections due to the giant blisters that form.

Penicillin

Penicillin is, of course, where antibiotic therapy all started. The story of its discovery may be old hat, but it’s one that embodies the fact that many scientific breakthroughs require luck most of all.

Antibiotic therapy was actually first discovered by French med student Ernest Duchesne in 1896. He performed a series of experiments ending in injecting a guinea-pig with a solution containing spores of Penicillium glaucum (producing what is now known as patulin, a less effective, but similar antibiotic to penicillin) and E. coli. The guinea-pig survived the E. coli infection, unlike its buddies who weren’t injected with the spores. He submitted his findings in his thesis and presumably wanted to do more work on this great discovery, but was instead forced into army service. He didn’t die in combat, but instead died of tuberculosis on April 12, 1912 as a 37 year old scientific nobody until he was honoured 5 years after Fleming and his pals received a Nobel Prize for their better known discovery of penicillin…

On his way out to vacation in 1928, Alexander Fleming left some agar plates inoculated with Staphylococci on the bench to grow. Before they were swabbed with the bacteria, a spore of Penicillium notatum had landed on the culture plate by chance. Even luckier, the weather was cool enough so that the mould grew faster than the staph and got a foothold on the plate rather than being overrun by it. When he came back, he found an entire plate of staph colonies except for a portion around a colony of what he discovered later as the penicillium mould.

However, after further experiments, Fleming thought that it’d be of no use in medicine because it’d be cleared from the body  through the urine before it did any good. He abandoned the idea in 1931. In 1939, Howard Florey was a professor in Oxford looking up stuff about bactericides and happened to come upon Fleming’s work. He and his co-worker Ernst Chain found a way to purify penicillin and did a merry jig when they found that it cured their diseased mice. Obviously it ended up working on humans as well. However, during the war, they could not produce enough for demand. As I mentioned before, a lot of the penicillin would be excreted in the urine. So, to solve this problem of demand, patients would end up reusing penicillin by drinking their pee. Anyway, long story short, Fleming, Florey and Chain got a third of a Nobel Prize each.

This discovery not only improved human suffering but also made certain medical research methods easier and catalysed a search for the 100-odd other antibiotics produced by other micro-organisms. Among these are: bacitracin, produced by a Bacillus licheniformis (from the same family as anthrax); Streptomycin, found in Streptomyces griseus; and vancomycin, which I’ll discuss next.

Vancomycin

Vancomycin works in a similar way to penicillin in that both kill the bacteria by stopping the production of their thick protein-sugar walls, which usually act as like a wire mesh acting as a supporting structure to stop the cell from exploding due to osmosis. One thing that’s also becoming comparable to the two is the way that bacteria are becoming resistant to it.

Vancomycin had become an antibiotic of last resort as others, such as penicillin, streptomycin, etc., have become useless against the increasing resistance of pathogens. But even this antibiotic has started to become ineffective against some species of bacteria due to natural selection. Unless we develop more new antibiotics and opt for more careful prescription, we risk reverting back to the dark ages of medical history. In my next article ,I’ll discuss experimental ways being developed to combat the rise in antibiotic resistance.

TT

Sources

Duchesne E (1897) Contribution à l’étude de la concurrence vitale chez les microorganismes – Antagonisme entre les moisissures et les microbes. Faculté de Médecine Lyon-Sud Laboratoire de Microbiologie. UMR CNRS 5558. (website accessed at http://lyon-sud.univ-lyon1.fr/bacterio/DOCDIV/duchesne.html).

Elsevier Publishing Company (1964). Physiology or Medicine 1942-1962. Nobel Lectures. Elsevier Publishing Company.

Garra GP, Viccello P (2005). Toxic Epidermal Necrolysis. eMedicine.com. (website accessed at http://www.emedicine.com/EMERG/topic599.htm).

Prescott LM, Harley JP, Klein DA (1999). Antimicrobial Chemotherapy. Microbiology (4th edition). McGraw Hill. Pgs 678 – 695.

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5 Comments

Filed under Thomas' Corner

5 responses to “(anti) Disease of the week: Antibiotics – Fighting fire with the gooey bits that come out of other fires

  1. “He submitted his findings in his thesis and presumably wanted to do more work on this great discovery, but was instead forced to fight in WWI. He didn’t die in WWI, but never got any work published on the antibiotic after it. He died on April 12, 1912 a 37 year old scientific nobody”

    Is the reason he didn’t die in world war one because he was already dead? Interesting if true. Do you think anyone noticed he was a zombie?

    Do you think antibiotics would have a greater therapeutic window in zombies than in regular humans? Something must be keeping their flesh from decaying…

    Interesting blog!

    • thomastu

      Thanks for picking that up, Lumpy. Appreciate the sarcasm. Have corrected it. Wrote it a while ago as a hopeless undergrad obviously. Will do a pub med search on “zombie AND antibiotic therapeutic window” when I get back into the lab. Will eventually stop producing sentence fragments.

      TT

  2. Pingback: De verborum notatio morbi – On the etymology of diseases « Disease of the Week!

  3. Genny

    Hi Thomas I read your article today in The Advertiser with a lot of interest as a friend has C.diff. I have Blastocystis Hominis which has similar problems. More studies should be done on this as it is very common and causes serious problems for me and really ruins your life style. It should be classed as a pathogen! Have you done any studies on this? I would welcome an email from you if you have the time.

    Good luck, and keep up the good work
    Regards,
    Genny

    • Thanks for the E-mail, Genn. I appreiate your comments. This is actually the first time I’ve heard of Blastocytis Hominis. Obviously with millions of different species of bacteria, it’s hard to keep track of them all. I will E-mail you soon.

      Cheers,
      Thomas

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