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Medicinal Chemistry

Teixobactin: A New Antibiotic, and A New Way to Find More

Teixobactin - The Newly Discovered Antibiotic
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If you’ve read any science news over the past day or so, you’ll have noticed it’s been dominated by stories about the discovery of a new antibiotic, teixobactin. There’s a reason that the scientific community is so excited by its discovery, but in truth, it’s the method which was used to discover it as much as the compound itself that’s drawn attention. Today’s graphic gives you a run-down of the key points.

Teixobactin’s discovery has the potential to be a big deal. If it eventually gets approval for clinical use, it’d become the initial member of the first new major class of antibiotics for at least a decade. A lot of news outlets have touted it as ‘the first new antibiotic for 30 years’; this isn’t strictly the case, however, as new drugs in existing antibiotic classes have been discovered more recently. Whether it’s the first new class of antibiotics for a decade rather depends on how they are defined. The summary graphic below, from a previous post on antibiotics, shows a selection of the main classes and their discovery dates:

Main Classes of Antibiotics Summary
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Of course, it’s not just the fact that it’s the first major antibiotic discovery for a little while that’s got people interested. Another factor is that the researchers who published the study suggest that, due to the manner in which teixobactin acts on bacteria, it should prove difficult for them to quickly become resistant to it. Teixobactin works by binding to lipid (fat) molecules that the bacteria use to build cell walls, thus rendering them unable to do so. This results in a weakened cell wall, which eventually leads to bacteria bursting and dying. Due to the fact that the target of the antibiotic isn’t easily modifiable by the bacteria, it’s thought that resistance would take much longer to develop – perhaps as long as 30 years – though it would eventually appear to some extent.

Teixobactin does have its drawbacks, primarily that it’s still only been tested in mice. It was so effective in killing bacteria, that the researchers working on it were concerned that it would also be toxic to mammalian cells, but this was not the case. Still, years of clinical trials in humans await before teixobactin will be available for medical use in humans. Additionally, the research in mice was carried out using intravenous injection of the compound, and it seems likely that in humans, too, the antibiotic would have to be injected rather than taken as an oral tablet.

Another issue is that teixobactin isn’t effective against all bacteria. There are two classifications of bacteria, gram-positive and gram-negative, and the extra membrane around the cell wall that the gram-negative bacteria possess means that teixobactin has no effect on them. This is unfortunate, as harmful bacteria such as E. coli are included in the gram-negative group – though MRSA is a gram-positive bacteria, so teixobactin could be used to combat antibiotic-resistant strains.

Whilst the discovery of teixobactin is great news, perhaps even better is the method used to discover it. We know bacteria produce their own antibacterial compounds, to combat other competing bacteria. However, since 99% of bacteria can’t be grown in lab conditions, this greatly limits the number of these compounds that we can investigate. The method used to discover teixobactin overcomes this, by diluting soil samples, then placing small samples containing single bacterium cells in a device they named an ‘iChip’.

The ‘iChip’ is essentially just a device with a large number of small channels, into which bacteria can be deposited. The channels are then covered with a semi-permeable membrane, which allows environmental factors which influence bacterial cell growth to diffuse across to the bacterium cells. Using this method, the researchers were able to cultivate bacteria which were not previously grown in lab conditions, as once a culture is formed it is easier to entice them to do so. The researchers isolated 25 different antibiotic compounds, of which teixobactin is the most promising. This method has the potential to be a huge advance, and could lead to more possible antibiotic candidates in the future.

We won’t know how effective this method for producing antibiotics is for some time, but the number of compounds produced by various bacteria is vast, so the potential is there. If you want to read more about both teixobactin and the method used to produce it, the paper itself is open access.

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17 replies on “Teixobactin: A New Antibiotic, and A New Way to Find More”

Inter­esting article, but this com­pound is at least 3–4 years behind another sim­ilar antibi­otic that I haven’t seen get the atten­tion it deserves. The one I’m talking about just fin­ished Phase 2B trials, was granted QIDP status under the GAIN act, and has had results that match or sur­pass Daptomycin’s 7 day treat­ment either as a 3 day or as a 1 day course of treat­ment! Even better, testing indi­cates that bac­te­rial resis­tance is extremely unlikely to develop. The com­pany is Cell­ceutix, and one of their leading drugs in devel­op­ment, Brilacidin, also attacks the bac­teria cell walls. Right now, it’s going into Phase 3 for severe skin infec­tions, such as MRSA and other resis­tant super­bugs. What to know about it: attacks bac­te­rial cell walls, single dose treat­ment has proven very effec­tive with min­imal drug-​​related side effects, works just like host defense pro­teins. It’s part of a new class of antibi­otics called Defensin Mimetics. Bac­teria would need to evolve an entire new cell wall struc­ture to develop immu­nity, sim­i­larly to Teixobactin, only this drug is a lot fur­ther along in the approval process! Also, Cell­ceutix has devel­oped a room-​​temperature stable com­pound and are going to start a Phase 2 trial on Dia­betic Foot Ulcers shortly! You can Google it and check out some of the company’s press releases, including pub­lished results! This research is the tip of the iceberg!

There are certainly a number of other agents also in trials; I guess, generally, the reason to be excited about teixobactin is because of the method used to discover it, rather than teixobactin itself. As I mentioned above, the headlines which have claimed it’s the first new antibiotic to be discovered in 30 years are certainly wide of the mark.

Another example of an antibiotic which could make it to approval before teixobactin is platensimycin (http://www.nature.com/nature/journal/v441/n7091/abs/nature04784.html). That’s also still preclinical, however, which shows how long it can take for a drug to reach clinical use after its discovery.

[…] The common symptom, that of a blocked nose, is probably one of the most irritating, but thankfully, nasal decongestants exist to provide relief. But how do they work? Generally, decongestants exert their effects by constricting blood vessels. They act on alpha-adrenergic receptors in the nose and sinuses in order to cause this vasoconstriction, which subsequently helps to reduce inflammation and the formation of mucus in the nose. A number of different drugs can be used to induce these effects, but some of the most commonly used are shown in the graphic. Teixobactin: A New Antibiotic, and A New Way to Find More. […]

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