Positive for Gram Positive?

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Way, way back in 1928, Arthur Fleming, who was working at St. Mary’s Hospital, found a contaminant amongst his petri dishes laden with Staphylococcus aureus. It’s not unusual for microbial petri dishes to be contaminated- and we continually strive to improve our practices to insure this is not the case.  (It certainly was more prevalent in the past.)

Fleming’s problem was a strain of Penicillium notatum. But, the real finding, as he observed on 28 September 1928, was that this invading strain precluded the growth of Staph on that petri dish.

So, I am sure all of you immediately jump to the conclusion that “that was that”- and penicillin was now going to be used as the first antibiotic to help cure sick patients.

Wrong. We needed to find a way to purify the material and render it usable in patients. That task was left to Drs. Howard Florey and Ernest Chain of Oxford University. And, that was reduced to practice in 1938- a full 10 years later. And, the first patient to receive the treatment had to wait four more years.

That’s not an atypical course of events. So, Drs. Kim Lewis and Slava Epstein of Northeastern will need to speed up their development and purification of teixobactin to make it useful for humans. This antibiotic is produced by a microbe that had not been grown in the lab before, Eleftheria terrae.

These folks did something a lot of researchers used to do. (And, obviously some still do.) About 45 years ago, I took samples from the Boston Common soil to harvest microbes that could be of use in my thesis- the degradation of honest-to-goodness solid waste. You also should know that more than ¾ of all potential antibiotics have been derived from microbial strains (or fungi) that have been found in our environment- but only about 1 in 100 can be grown in the lab- which means testing and scale-up are not directly in the offing. (Yes, that means finding the microbes is not the hard part- but growing them and purifying them are the primary challenges.)

iChip
iChip in soil, NY Times, photo taken by Slava Epstein

Like my forays, these two doctors headed up a multinational group (funded by the US’ NIH, as well as German sources) that found what they wanted- a new class of antibiotic- by examining some 10,000 strains they were able to isolate from the soils in Maine. They published these results in Nature. At least they know it’s effective and safe in mice- now we need to find if it works in humans. Oh, and develop a method to mass produce and purify the drug.

iChip
From the Wall Street Journal

But, the real improvement is that Lewis and Epstein developed a device they call an “iChip”, which is described in the diagram above.  They “infect” each cell in the iChip with different microbes and then bury the device in the soil. Then, these microbes that don’t like laboratory conditions can actually thrive and grow into full colonies.

Teixobactin

These colonies are then placed on petri dishes and candidate “infections” like Staph and Strep (this is shorthand for the genus Streptococcus)  are overlayed on the dishes. And, clear zones- which indicate the effectiveness of the potential antibiotic against the infection- are identified. And, that’s how one goes about isolating an antibiotic among the 10,000 candidate strains.

(By the way, Staph- and other similar microbes are “Gram-positive”- that means they show up clearly under the microscope when tested with Gram stains. Dr. Gram developed this technique some 150 years ago (1884) is a major method of classifying microbes. This new antibiotic is ineffective again gram-negative infections- pneumonia, cholera, gonorrhea, and others.)

And, as opposed to penicillin, this new antibiotic binds to multiple targets and blocks the fat molecules from joining the microbial cell wall; this renders the cell wall virtually useless. (The cell wall is what the Gram procedures actually “stain”. It’s the Gram positive microbes that have cell walls.) And, it seems that the course of action is one that will limit the development of bacterial resistance to the drug.

Let’s hope this development doesn’t take a whole decade, either.  Because MRSA (methicillin-resistant Staphylococcus aureus) will be killing too many in that period.

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