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Leftovers


Alexandra N. Martirossian
Vincent Valentine, MD

Vgvalent@utmb.edu
University of Texas Medical Branch
Galveston, TX, USA



As the holidays draw ever nearer, perhaps people all over the world will brace themselves for a grueling season of feasting. On Thanksgiving Day in the United States, kitchens will be overflowing with the edible goodness of roasted turkey, stuffing, gravy, cranberry sauce, mashed potatoes, sweet potatoes, green bean casserole, and Grandma's famous pumpkin pie. After uncomfortably tight waistbands herald the end of the feast, the preparers of the meal will be faced with a new challenge: what to do with all the leftovers. Purists will argue that leftovers must be consumed in their original form whereas the more adventurous eaters may transform the ingredients into a new dish entirely. Regardless of how they are consumed, if too much time elapses, any uneaten vittles may become the subject of a biology project. Although the appearance of blue fuzz typically indicates that a food is destined for the trash can, it could also be the first sign of a medical breakthrough.

Like many great discoveries in science, the antibiotic penicillin was discovered serendipitously. In 1928, Alexander Fleming, a microbiologist on the faculty at St. Mary's hospital in London, neglected to clear away his Petri dishes of Staphylococcus before heading out for a weekend vacation [1]. When he returned to his lab after the weekend, he was greeted by both a messy lab bench and a peculiar finding. Inspection of his bacterial plates revealed that the plates had been contaminated with mold and that the bacteria growing closest to the mold were undergoing lysis. Thrilled by this finding, Fleming eagerly attempted to repeat the experiment, but it turned out this exact strain of Penicillium chrysogenum mold was more difficult to grow than he had anticipated. It was Fleming's colleague Ronald Hare who figured out that the mold grew and produced this "bacteriolytic substance" optimally at a low temperature of 20°C [1,2]. In subsequent experiments, Fleming took the "mould broth filtrate" from this special P. chrysogenum strain and added it to various bacterial strains that were pathogenic in humans to assess its antimicrobial activity. For the sake of convenience when publishing his results, Fleming substituted the lengthy phrase "mould broth filtrate" for "penicillin," and hence gave this now ubiquitous antibiotic its name [2]. Fleming's experiments yielded the findings that penicillin was ineffective at killing Gram negative bacilli, but was very effective at killing Gram positive cocci such as Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes [2].

As significant as Fleming's findings were, there existed the practical issue of generating enough penicillin from the mold to make it available for mass distribution. As World War II encroached on Europe, interest in finding treatments for infections and other illnesses that befell soldiers grew, so Dr. Howard Florey, a professor of pathology at Oxford University, and several of his colleagues accepted the challenge of making penicillin more widely available [3]. In the summer of 1941, shortly before the United States entered the war, Florey and his colleagues traveled to Peoria, Illinois to continue their research. They were particularly interested in finding a P. chrysogenum strain that was capable of producing copious amounts of penicillin, so they solicited international assistance by asking for donations of lab samples, moldy fruit, grains, and vegetables [1]. After much searching, the solution finally arrived in the form of a moldy cantaloupe brought in by a Peoria housewife. With laboratory manipulation of this P. chrysogenum strain, penicillin production jumped from a humble 4 units/mL to 250 units/mL. Today, industrial P. chrysogenum strains can produce 50,000 units/mL of penicillin, and these strains are still believed to be derivatives of the strain isolated from the Peoria cantaloupe. In the war, penicillin significantly reduced mortality related to pneumococcal infection, and in 1945, Fleming, Florey, and Dr. Ernest Chain, a chemist on Florey's Oxford team, were awarded the Nobel Prize in Medicine [3].

From a scientific standpoint, Penicillium chrysogenum could be considered a multitalented fungus because it has shown potential in synthesizing a variety of products. Penicillin, its most famous product, falls under the classification of beta-lactam antibiotics, a large group that also includes cephalosporins, carbapenems, and monobactams [4]. These drugs vary widely in their spectrum of coverage, but they share a common chemical structure of the beta-lactam ring as well as a common mechanism of inhibiting the synthesis of the bacterial peptidoglycan cell well. Penicillin was once the treatment of choice for the common pathogens Streptococcus pneumoniae and Staphylococcus aureus, but due to growing resistance over the years, alternative antibiotics are now frequently used. Despite this growing resistance, penicillin is still the treatment of choice for conditions associated with Streptococcus pyogenes infection (e.g. Streptococcal pharyngitis, rheumatic fever, scarlet fever, toxic shock syndrome, necrotizing fasciitis, and erysipelas), meningococcal disease, syphilis, actinomycosis, gas gangrene, and Pasteurella multocida. In addition to its well-documented utility in the synthesis of an antibiotic, P. chrysogenum has shown potential in the production of the lipid-lowering drug pravastatin [5]. Breaking out from the field of medicine, P. chrysogenum may also have a future in the production of sweet wine [6].

At the conclusion of his Nobel lecture in 1945, Fleming summarized the beginning of his work with penicillin by describing P. chrysogenum as "a mould which was not wanted…[that] contaminated one of my culture plates…[and] produced an effect which demanded investigation" [7]. In Fleming's case, seeing value in this unwanted organism led to the development of a drug that has significantly impacted medical practice. From this historical event, we can see that sometimes the things that are undesirable may prove to be more valuable than we anticipate. With this principle in mind, we should approach this season of feasting with a new mentality: Bring on the leftovers! ■

Disclosure Statement: The authors have no conflicts of interest to disclose.


References:

  1. Volk, Thomas (2003). "Tom Volk's Fungus of the Month for November 2003." Department of Biology, University of Wisconsin-La Crosse. Retrieved from http://botit.botany.wisc.edu/toms_fungi/nov2003.html
  2. Fleming, Alexander (1929). On the antibacterial action of cultures of a Penicillium, with special reference to their use in the isolation of B. influenzae. British Journal of Experimental Pathology, 10, 226-236.
  3. Markel, Howard (2013, September 27). "The Real Story Behind Penicillin". PBS NewsHour. Retrieved from http://www.pbs.org/newshour/rundown/the-real-story-behind-the-worlds-first-antibiotic/
  4. Brunton, Laurence L., Chabner, Bruce A., and Knollmann, Björn C. (2011). Chapter 53: Penicillins, Cephalosporins, and Other Beta-Lactam Antiobiotics. In Goodman & Gilman's The Pharmacological Basis of Therapeutics (12th ed). China: McGraw-Hill.
  5. McLean, Kirsty J., et al (2015, March 3). Single-step fermentative production of the cholesterol-lowering drug pravastatin via reprogramming of Penicillium chrysogenum. PNAS, 112 (9), 2847-2852.
  6. Garcia-Martinez, Teresa, et al (2015). Natural sweet wine production by repeated use of yeast cells immobilized on Penicillium chrysogenum. LWT-Food Science and Technology, 61, 503-509.
  7. Fleming, Alexander (1945, December 11). Nobel lecture: Penicillin. NobelPrize.org. Retrieved from http://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-lecture.pdf



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