Dr Jim Robinson looks at a promising piece of news published in January this year.
Ever heard of Teixobactin?
Chances are we will all be talking about it in the next decade and long after. With a nice rural introduction saying something like “from a handful of dirt from a grassy field in Maine …” a new and potentially important family of antibiotics has been unearthed, so to speak.A bacterium, Eleftheria terrae by name, has been isolated by an amazing method of screening random samples. This involves a complicated isolation method called iChip, which demands microbiological precision and expertise way beyond the grasp of this non-microbiologist, and ends up growing a single cell in a medium that allows it to multiply and produce whatever it does normally, but in an unrestricted way and without competition.
It turns out that at least one such isolate has bactericidal properties.
After 30 or so years, a new family of antibiotics?
E terrae is a bacterium that produces a new compound that kills other bacteria selectively, does not damage the tissues of animals or man, and works in ways that make it unlikely to produce resistant strains of target bacteria. What makes teixobactin exciting is a number of differences from the long run of fungus-derived antimicrobials, which have been saving millions of lives since 1928 and penicillin.
• It must have come as a surprise to the researchers to find that a bacterium, not a fungus, is producing the next range of bactericidal products;
• Its spectrum of action is narrower than many of the more recent broad spectrum anti-microbials, being active almost exclusively against Gram positive organisms;
• Its mode of action is to prevent the synthesis of bacterial cell walls by binding with a lipid precursor of a (peptidoglycan) layer which is necessary for the target bacterium to survive. Gram negatives which include E. coli, salmonellas, other enterobacteria, pateurellas, actinobacillus, hemophilus and many others, have an outer protective membrane which is not susceptible to attack by teixobactin.
What does it kill?
Most of the staphylococci, streptococci, bacilli, mycobacteria, clostridia, corynebacteria and others.
Most importantly, it has been found to be effective against three or more of the current infective heavyweights giving the curative professions the worst time. These are:
• MRSA or methicillin resistant staphylococcus aureus, a particularly vicious Staph that is strongly resistant to penicillin and its relations. It causes serious skin infections, operation wound contamination, pneumonias and can
kill with a septicaemic form. It is one of the notorious nosocomial infections, ie it is in the hospital environment, in many cases. It has been isolated in pigs.
• MDRTB or multiple resistant tuberculosis, causing increasing concern with the ever smaller list of effective antibiotics.
• Of interest is that as pigs are susceptible to all three variants of mycobacteria, they may conceivably become infected with the MDRTB human strain and act as carriers in piggeries.
• CDI or Clostridium difficile infection, a mainly hospital-related cause of persistent and recurrent enteritis in humans, but related to other clostridia which we know well, like Cl perfringens with its various types, Cl novyi, the cause of gas gangrene in animals and Cl botulinum, which produces perhaps the most toxic nerve toxin known and consequently a favourite for biological warfare.
• Bacillus anthracis or anthrax, another strong candidate for “germ warfare”, a world-wide and frequently occurring infection killing cattle and other ruminants in unprotected herds.
Pigs are susceptible but mortality rates are low and, as soil is the usual infective source, it is outdoor herds that are more vulnerable.
New and more virulent strains are no doubt being cultured in secret—the envelope containing a whitish powder (the dried but living spores) is already encountered in the movies if not for real with a capability to cause different syndromes in man, all serious.
These vary from persistent carbuncles in the skin to rapidly fatal pneumonia.
Infection with the well-known ancient strain occurs now usually through eating dead animals, but used to be called “milk maids’ disease” because the infection – by long-living anthrax spores contaminating the teats pf cows – entered the cracked skin of milkers.
The resistance bogey
Perhaps the most encouraging aspect of this new emerging cluster of antibiotics is its mode of action. We all know that antibiotic resistance is becoming more problematic, although much less so than some pressure groups would have us believe.
Several interdependent activities are involved in producing a resistant pathogen:
Resistance in bacteria is due to spontaneous, random mutations which happen from time to time and the mutant cells are usually swamped and disappear.
If the antibiotic to which resistance has spontaneously developed is present in the immediate environment of the new rogue daughter cells, eg with treatment, the mutants will survive while the “normal” non-resistant ones will die.
This is selection and the cause of the trouble as well as all of evolution including the emergence of Homo sapiens, so don’t knock it.
The proteins of the bacterial wall are the most liable to mutate and are also the point of attack by many of the present armoury of antibiotics.
Teixobactin, although it also attacks the bacterial wall, targets the much less mutation-prone fatty molecules of the multi-layered covering, and the development of resistance will consequently be greatly reduced.
Registration and availability will take a long time, like ten years.
There may, almost certainly will, be related compounds from other soil bacteria, covering gram-negative pathogens so that a whole new batch of wonder drugs will hit the market and save millions of lives.
There will be a growing list of trials and results and reports, and there are very good historical reasons for the developers to complete effectivity and safety trials to the point where the new wonder-drug family can be launched with confidence.
ROLL ON 2025!!
CDC Atlanta, Nature, Wikivet, trade and newspaper articles cited by Wikipedia, Pig Progress.