Antibiotic Pioneers

In 1928, Scottish scientist Alexander Fleming was fiddling around with a strange mold he found growing on a Petri dish. This mold was known as Penicillium notatum and after an accidental exposure of the Penicillium to a Petri dish containing Staphylococcus (an infectious microbe), Fleming discovered that the exposure resulted in destruction of the Staphylococcus. This was an amazing discovery and he soon learned he now had the power of life and death over a wide range of Gram-positive bacteria that had been stymieing doctors for centuries!  Fleming toyed with the moldy medicine for well over a decade with little success in making a commercially viable, purified form of his invention: penicillin.

At about the same time, across the pond, U.S. scientist Selman Waksman was also tinkering with microbes and developing a long list of antibiotic compounds with targeted therapeutic value.  By the 1940’s his lab had developed streptomycin, chloramphenicol, and tetracycline, all produced by soil bacteria. Selman Waksman was a student of dirt. In 1927, he penned his treatise Principles of Soil Microbiology and continued to devote his life to studying the invisible life living in the mud of the Earth.  Soon, Dr. Waksman learned to harness this invisible life and by 1942, he was producing large quantities of these antibiotic molecules that would selectively lay waste to a large range of microbes. These antibiotics were far more powerful than Fleming’s penicillin, killing both Gram-negative and Gram-positive microbes...we now had complete control of the invisible life within us. His focus was on agriculture and keeping our crops healthy and profitable, but the 1940’s had bigger plans for Waksman’s efforts.

  

Dr. Waksman died in 1973, but the true depth of his contribution to modern society is just recently coming to light. The microbes may have indeed made this a better world to live in, but not for us—for them.  For, you see, what Dr. Waksman did not predict, or chose to ignore, microbes have a few tricks up their sleeve.  At the natural, tiny, ‘signalling molecule’ level, microbes play by the rules they developed over billions of years, but when continually slathered and bathed in the toxic substance, microbes won’t stand by and be wiped out—they adapt and overcome.

  

The bacteria of the world secrete over 2200 different antimicrobial peptides, known as AMPs, that have been so far cataloged.^{[11] [12] [13]}  In addition, our own immune cells known as Paneth cells secrete antimicrobial chemicals such as defensins and AMPs. The natural antibiotics and antifungals secreted by our silent commensals and our guts cells tend to be selective and targeted toward pathogenic species and not harmful toward themselves or non-infected tissues.^[14] Clinical doses of pharmaceutical antibiotics in relative comparison elicit carnage to a magnitude and scale akin to weapons of mass destruction. Both friends and foes are destroyed but what typically remains standing are the hearty pathogens which then take the initiative in the absence of our allies. Humans and animals all harbor ‘pathogenic’ strains of microbes like C. difficile, Staphylococcus, and haemolytic E. coli, yet neither infection nor disease may ever occur because the gut is guarded by plenty of beneficial commensals like Lactobacilli, Bifidobacteria, good E. coli, and other major microbial species.

Special thanks to Dr. Grace Liu, PHARMD, from Animal Pharm for contributions to this article.

[11] Nakatsuji, Teruaki, and Richard L Gallo. "Antimicrobial peptides: old molecules with new ideas." Journal of Investigative Dermatology 132 (2012): 887-895.

[12] Wang, Guangshun, Xia Li, and Zhe Wang. "APD2: the updated antimicrobial peptide database and its application in peptide design." Nucleic acids research 37.suppl 1 (2009): D933-D937.

[13] Silva, PM. "Defensins: antifungal lessons from eukaryotes." 2014. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960590/>

[14] Yeaman, Michael R, and Nannette Y Yount. "Mechanisms of antimicrobial peptide action and resistance." Pharmacological reviews 55.1 (2003): 27-55.