Antimicrobial resistance is an emerging threat that has increased exponentially since penicillin resistance was observed in the bacteria Staphylococcus aureus in 1947. The overuse of antibiotics in both therapeutic and agricultural use, along with other environmental and behavioural factors have contributed significantly to the ever increasing antimicrobial resistance in the many different strains of bacteria. This has greatly assisted some strains of bacteria in becoming resistant to multiple classes of drugs. Among some of the most common of these are methicillin-resistant Staph aureus (MRSA) and multiple-drug or extensively drug resistant tuberculosis (MDR-TB and XDR-TB).
With the slowing discovery of new drugs, particularly antibiotics, and the lack of funding towards expensive research on alternative treatments, the options available for the treatment of antimicrobial resistant strains of infectious diseases are limited. This has led to an increase in morbidity and mortality for patients with advanced infections.
New, targeted treatments may soon be developed with the current studies involving clustered regularly interspaced short palindromic repeats (CRISPR) design in next generation antimicrobials. CRISPRs are DNA sequences which are a part of a naturally occurring bacterial defence system that allows bacteria to incorporate foreign DNA and even scavenge foreign DNA from their environment. The clustered repeats were first discovered in 1987 in the bacterium E.coli by a Japanese scientist who, at the time, did not know what the function was.
CRISPR was proposed to be responsible for the generation of adaptive immunity in microbes. It has since been observed that CRISPRs could be used to edit various genomes in order to edit out disease, or even wipe out disease carrying organisms such as the Malaria carrying Anopheles mosquito.
There are some exciting discoveries that are to be made with CRISPR. A study recently published in Nature Biotechnology by Bikard et al., (2014) explored the possibility of using the CRISPR- associated protein 9 (Cas9) as a sequence- specific antimicrobial, a tool that would allow selective killing of one or more bacterial species within a heterogeneous population. They conclude in their study that “their strategy has several advantages over both small-molecule antibiotics and phage therapy.”
Another study published by Citorik, Mimee and Lu, (2014) in Nature Biotechnology also covering sequence-specific antimicrobials concludes their report with “by repurposing parts developed by nature, synthetic biologists have designed artificial gene circuits for antimalarial production and engineered probiotics and phage therapeutics to eradicate biofilms or potentiate antibiotic activity.”
Even though CRISPR is still in its early stages of bacterial resistance research, it is looking to be quite promising towards treating MDR bacteria.
Bikard, D., Euler, C., Jiang, W., Nussenzweig, P., Goldberg, G., Duportet, X., Fischetti, V. and Marraffini, L. (2014). Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials. Nat Biotechnol, 32(11), pp.1146-1150.
Citorik, R., Mimee, M. and Lu, T. (2014). Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases. Nat Biotechnol, 32(11), pp.1141-1145.