Teixobactin was discovered using a new method of culturing bacteria in soil, which allowed researchers to grow a previously unculturable bacteria now named Eleftheria terrae, which produces the antibiotic. In the Nature study, teixobactin was shown to kill Staphylococcus aureus or Mycobacterium tuberculosis without the bacteria developing resistance.
I totally agree that its a natural compound from soil bacteria.
Resistance to newer antimicrobial compounds develops over the time.
It is important to realiize that most of the microbes have come across each other (even before human existence) and there is definitely memory in them against such compound ought to harm them.
To be optimistic we are definitely going to be more than happy to have such antimicrobial compound against which microbes would never develop resistance.
Source: Wikipedia
Antibacterial activity
Mechanism of action
Teixobactin is an inhibitor of cell wall synthesis that acts primarily by binding to lipid II, a fatty molecule which is a precursor to peptidoglycan. This is similar to the action of the antibiotic vancomycin. Binding of teixobactin to lipid precursors inhibits production of the peptidoglycan layer, leading to lysis of vulnerable bacteria.
Activity
Teixobactin was reported to be potent in vitro against most Gram positive bacteria, including Staphylococcus aureus and difficult-to-treat enterococci and Mycobacterium tuberculosis, with Clostridium difficile and Bacillus anthracis being exceptionally vulnerable. It was also found to be effective in vivo, when used to treat mice infected with methicillin-resistant S. aureus (MRSA), and Streptococcus pneumoniae. The dose required to achieve 50% survival against MRSA is only 10% of the PD50 dose of vancomycin, an antibiotic typically used for MRSA.
It is not active against bacteria with an outer membrane such as gram negative pathogens, particularly carbapenem resistant enterobacteriaceae, or those with New Delhi metallo-beta-lactamase 1 (NDM1).
Induction of resistance
No resistant strain of S. aureus or M. tuberculosis was generated in vitro when administering sublethal doses, for as long as 27 days in the case of the former. It is postulated that teixobactin is more robust against mutation of the target pathogens, because of its unusual antibiotic mechanism of binding to less mutable fatty molecules rather than binding to relatively mutable proteins in the bacterial cell.
It is important to note that-
It is NOT ACTIVE against bacteria with an outer membrane such as gram negative pathogens, particularly carbapenem resistant enterobacteriaceae, or those with New Delhi metallo-beta-lactamase 1 (NDM1).
Since this antimicrobial is produced in the environment by microbes, by definition, there must be resistance traits out there against this compound. Just because the strains used in the lab didn't reach resistance it doesn't mean there isn't a bacterium somewhere in the environment that cannot become resistant over time or one that doesn't possess a resistance gene capable of being transferred to other bacteria.
S. aureus and M. tuberculosis have shown no resistance upon culturing for few days on sublethal concentration of teixobactin. It does'nt mean that there will be no resistance. In M. tuberculosis, a slow growing bacteria, resistance development requires more time, and in some cases, successive contacts with the Drug. Even Teixobactin act on lipids, don't forget that there are other mechanisms of resistance by efflux pumps or others (ABC) tranposters.
Teixobactin is active against only Gram-positive bacteria and M. tuberculosis. In recently published nature paper, Kim Lewis et al. claimed no detectable resistance observed in Staphylococci and Mycobacteria after 4 weeks of serial exposure to new molecule whereas the control antibiotic ofloxacin promote resistance in bacteria. Ofloxacin is a fluoroquinolone class of antibiotic that inhibits DNA gyrase thereby halting the DNA synthesis. Generally, it is known in the literature that antibiotics that directly act on gene material (DNA) would trigger resistance faster compared to the other classes of antibiotics due to genetic mutations (Reacticve oxygen species production). Here they claim that this molecule is cell wall biosynthesis inhibitor. For the resistance development experiment, they had used fluoroquinolones. They should have used one of the cell wall biosynthesis inhibitor such as vancomycin, methicillin etc. as a positive control. This probably limits their strong claim "no detectable resistance". Also they claimed this molecule binds to negatively charged pyrophosphate present in lipid II probably due to the presence of cyclic guanidine which becomes positively charged under physiological conditions. Another clinically approved antibiotic that acts on lipids (LPS of Gram-negative bacteria) is colistin. Initially, scientists thought that bacteria probably would be unable to develop resistance to colistin. But, before getting FDA approval bacteria acquired resistance to colistin by modifying their lipids from more negatively charged LPS to less negatively charged to further zwitter ionic and in some cases you find positively charged lipds in colistin-resistant bacteria. In my opinion, bacteria after exposing to teixobactin, if we analyze the lipid content of these bacteria we would definitely observe altering of lipids. And also, teixobactin is naturally occurring compound probably resistance might have been already existed in the environment. It just a matter of time (probably soon), pathogenic bacteria would acquire resistance definitely to teixobactin.
The effective way to tackle bacterial resistance is through multi-pronged approach. Not through just one single mechanism but through multimodal mechanism of action wherein bacteria really face a difficulty to acquire resistance.
http://pubs.acs.org/doi/abs/10.1021/jm500270w
All of you how can I purchase Teixobactin , any manufactures name, thank you a lot
Dear Yasar the antibiotic compound to be available in the market would take at least couple of years more.
It should be mentioned too that it is claimed that teixobactin has two or more mechanisms of action binding to lipid II and lipid III. It is argued that drugs with multiple modes of action will develop resistance more slowly that this with one. There is no evidence as yet that resistance won't develop against teixobactin, only time will tell although there is some data out there showing that resistance develops more slowly in drugs with a target other than a protein. It appears that lead optimisation is still ongoing with attempts to make a a more synthetically viable analogue so there is still a long way to go if it is to reach the clinic. Completely agree that the ichip is an equally exciting development.
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