BLOG: Is the iChip the new answer to antibiotic resistance?

Antibiotic resistance threatens to return us to the 19th century, where the smallest of cuts could be life threatening and the sterile environment required for surgery impossible.1,2

Antibiotic drugs are used to kill harmful bacteria that would otherwise cause infection. However, resistance arises when bacteria reproduce. The quick rate of reproduction often leads to mistakes when DNA is copied, resulting in mutations. Since DNA determines the physical and behavioural characteristics of bacteria, every so often the consequent mutation causes sufficient change such that an antibiotic is no longer effective. These resistant bacteria can then survive and so continue to reproduce, building a new population that will not be affected by the original antibiotic.

Following the discovery of penicillin in 1928,3 new classes of antibiotics were quickly discovered by analysing fungi and bacteria that produce their own antibiotics in the fight for survival.4 Unfortunately, the fact that the bacteria must be grown outside their natural (soil) environment has presented a major problem. Only 1% of all external species can be grown in the lab – leaving 99% that cannot be analysed.4,5

As it stands, only two new classes of antibiotic have been discovered since 1962,6 and misuse and lack of regulation has lead to more and more multi-drug-resistant bacteria.7 For these reasons, treatable diseases such as tuberculosis may once again become incurable.8 A study in the British Journal of Pharmacology estimates that we will need “a further 20 novel classes of antibiotics to support modern medicine during the next 50 years”.6 The challenge is in finding new ways that we can use the natural process of antibiotic production, employed by bacteria and yeast in the soil, to our advantage.

In one approach, researchers at Imperial College London have genetically engineered baker’s yeast to produce and secrete the antibiotic penicillin. Although the researchers are yet to discover a new antibiotic drug, the technique holds promise for future experimentation that could achieve this aim.9,10 However, this method is still in its infancy and as such there are likely to be obstacles that will need to be overcome before the approach can be realised.11

Genetic modification is also being implemented to sample existing organisms that secrete antibiotics, with the aim of identifying the section of DNA responsible for their production. Scientists intend to use this knowledge to engineer bacteria that can produce the existing antibiotics in the hope that they may evolve to make new ones. Although promising in theory, this too is far from yielding any viable results in humans. As such, years of testing are required to determine whether a new class of antibiotics can be discovered using this approach.<sup>12</sup>

A novel method of cultivation uses an iChip (i.e., isolation chip), which is placed in soil to trick bacteria into growing naturally despite being trapped: see Figure 1. The iChip allows bacteria to be grown in labs as a means to discover new classes of antibiotics.9 The technology offers a tangible method of antibiotic discovery that has not been possible with competing solutions as it grants access to soil bacteria that could not previously be grown in a laboratory setting.13 At the beginning of the process, the electronic chip is placed into water-saturated soil, allowing the tiny holes in the chip to catch individual bacteria. After the holes are secured with a semi-permeable membrane, the chip is placed back into the soil. This membrane traps the bacteria in place, but allows it access to the nutrients and water required for growth. Any antibiotic produced can then be removed and analysed for identification.4

The iChip has led to the discovery of teixobactin, which has proven to be effective against types of MRSA and tuberculosis that were previously considered drug-resistant. As published in Nature,5 teixobactin works by stopping the bacteria from making their protective cell walls, causing them to burst. There are limitations however; even with this technique, only 50% of natural bacteria are successfully cultured. Although this result represents a vast improvement on the previous 1%, there is still scope for development.

For now, sampling of new strains of bacteria using the iChip must continue. Further clinical testing with teixobactin is required to determine its efficacy and industrial viability as a prescription drug. This process is likely to take well over 10 years and require a lot of financial resources.14

Successful application of this technology may lead to the discovery of many new classes of antibiotic drugs, which could keep us ahead in the race against infection. This method will likely be optimised and scaled up to efficiently analyse larger amounts of bacteria in the coming years.

To conclude, the invention of the iChip has allowed us to grow and analyse bacteria that have never been cultured before. As a mechanism for survival, these bacteria often produce antibiotic chemicals, allowing us to extract them for identification. This has led to the discovery of a new class of antibiotic – teixobactin – which has been seen to successfully kill previously-resistant bacterial strains. Although the iChip may not be the golden bullet for antibiotic resistance, it offers a new technique that may yield many new antibiotic classes that could potentially save many lives in the future.

References

1. T. Sealey. Life before antibiotics (and maybe life after an antibiotic apocalypse). BBC [Internet].
2. J. Steenhuysen. Drug pipeline for worst superbugs “on life support”: report. Reuters [Internet].
3. A. Fleming. The discovery of penicillin. Br Med Bull. 1944;454–5.
4. A. Gründling. New class of antibiotics discovered – and why there may be more to come. The Conversation [Internet].
5. L. Ling. A new antibiotic kills pathogens without detectable resistance. Nature. 2015;0:1–4.
6. A. R. Coates, G. Halls, and Y. Hu. Novel classes of antibiotics or more of the same? Br. J. Pharmacol. 2011;163(1):184–94.
7. R. M. Anderson. The pandemic of antibiotic resistance. Nat. Med. 1999;5(2):147–9.
8. WHO. The world is running out of antibiotics, WHO report confirms. [Internet].
9. A. R. Awan, B. A. Blount, D. J. Bell, W. M. Shaw, J. C. H. Ho, R. M. McKiernan, and T. Ellis. Biosynthesis of the antibiotic nonribosomal peptide penicillin in baker’s yeast. Nat. Commun. 2017;8:15202.
10. LABMATE. Harvesting penicillin from yeast cells [Internet].
11. C. Smith. Scientists engineer baker’s yeast to produce penicillin molecules. [Internet].
12. A. Zipperer, M. C. Konnerth, C. Laux, A. Berscheid, D. Janek, C. Weidenmaier, M. Burian, et al. Corrigendum: Human commensals producing a novel antibiotic impair pathogen colonization. Nature. 2016;539(7628):314–314.
13. S. Knapton. First new antibiotic in 30 years discovered in major breakthrough The Telegraph [Internet].
14. U.S. Food & Drug Administration. Step 3: Clinical Research. [Internet].
15. D. Nichols, N. Cahoon, E. M. Trakhtenberg, L. Pham, A, Mehta, A. Belanger, T. Kanigan, K. Lewis, and S. S. Epstein. Use of Ichip for high-throughput in situ cultivation of “uncultivable” microbial species. Appl. Environ. Microbiol. 2010;76(8):2445–50.

About the Author

Books