Rather than withdrawal of these antibiotics from widespread usage, one way to approach this crisis is to introduce new antibiotics that kill the resistant mutants. Luckily, researchers in Hong Kong have recently synthesised a new antibiotic that aims to counter this problem.
Once glorious years of the antibiotic now in decline
The development of large numbers of antibiotics over the past few decades has caused much complacency over the looming threat of bacterial resistance. As a result of chromosomal changes or the exchange of genetic material, bacteria evolve naturally through the mechanism of natural selection and random mutation.
The paradox of the antibiotics regime is that Streptococcus pneumoniae, Streptococcus pyogenes, and staphylococci, which are the main organisms that cause the most common respiratory and cutaneous infections such as diarrhoea, urinary infection, and sepsis, are now resistant to virtually all of the older antibiotics. The extensive use of antibiotics in the community and nosocomial usage has fuelled this crisis.
Unfortunately, in recent years, the pharmaceutical industry has hardly been producing new antibiotics, particularly against Gram-negative organisms, to replace antibiotics that are no longer effective for many types of infection. This has been attributed to the lower profit margins for antibiotics as opposed to drugs for cancers or heart diseases.
However, this make the recent breakthrough by scientists in Hong Kong who have successfully synthesised a novel antibiotic known as teixobactin, which was discovered last year, all the more exciting and relevant.
Emergence of a novel antibiotic - Teixobactin
Teixobactin, which has been successfully isolated from uncultured bacteria, and contains promising properties has emerged as an alternative source of new antibiotics. It is currently being considered as a drug candidate for clinical development.
Teixobactin displays excellent activities against an array of the aforementioned Gram-positive pathogens. Given that the molecular target of teixobactin is not an endogenous protein, mutant strains of Staphylococcus aureus or Mycobacterium tuberculosis that are resistant to teixobactin have not been obtained despite repetitive treatments. Compared with other lipid II inhibitors, teixobactin has a less complex structure which binds to lipid II differently from others.
However, despite the potential that it has, teixobactin is not yet perfect, and the research team is keen to improve its clinical properties through structural modification, in partnership with a chemist from the University of Central Florida in the US.
The researchers utilised an efficient strategy to generate ten promising teixobactin derivatives in a fast and combinatory manner. Currently, a US patent has been filed for these derivatives. The scientists now aim to produce 100 different teixobactin derivatives within two years.
On a similar note, the genomics route has proven to have great potential; however it has yet to lead to the introduction of a marketed antibiotic. Developing new antibiotics which target non-multiplying bacteria is a key approach that may lead to drugs which can reduce the emergence of antibiotic resistance and increase patient compliance by shortening the duration of antibiotic therapy.
These new discovery routes have given rise to compounds that are in preclinical development, but, ultimately mechanisms such as antibiotic control programs, better hygiene, and synthesis of agents with improved antimicrobial activity need to be adopted in order to limit bacterial resistance. MIMS
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