CRISPR-based strategies in combating antibiotic resistance

Husna, Amity University Kolkata

What is Antibiotic resistance (AR)?

Antibiotic resistance (AR) is the biological phenomenon that occurs when germs like bacteria become resistant to an antibiotic and develop an ability to defeat the drugs that are designed to kill the bacteria. That means the bacteria continue to grow instead of getting killed by the antibiotic, causing severe infections which are sometimes impossible to treat. As the antibiotics become less effective, infections like pneumonia, tuberculosis, gonorrhoea, blood poisoning, and some food-borne diseases are sometimes impossible to treat. Hence, antibiotic resistance has become a big threat to global public health as it is rising to dangerously high levels in all parts of the world.

The Antibiotic resistance crisis

Recently, the application of novel CRISPR-based genetic approaches to reduce Antibiotic resistance (AR) in both environmental and clinical settings and prolong the utility of vital antibiotics has been examined. AR has become prevalent in medical facilities and the environment due to the widespread over-prescription of antibiotics and their misuse in animal husbandry. The environmental sources of AR are transmitted to human populations via bacterial intermediates which contribute significantly to the current health crisis of failure from antibiotic treatment. Health experts have predicted that AR threats, if left unchecked, could markedly worsen in the coming decades, leading to some 10 million AR disease deaths per year by 2050. 

Currently, antibiotic resistance (AR) is estimated to cost 700,000 lives annually.

CRISPR-Based Strategies to fight AR

CRISPR (clustered regularly interspaced short palindromic repeats) discovery has given rise to a revolution in precision genetic engineering in both prokaryotic and eukaryotic organisms. These sequences of CRISPR are derived from DNA fragments of bacteriophages that had previously infected the prokaryote so they have the ability to detect and destroy DNA from similar bacteriophages during subsequent infections. Some synthetic CRISPR systems have been developed to combat antibiotic resistance (AR). 

Two horizontal gene transfer (HGT) systems have been developed for spreading CRISPR-based anti-AR components. The first makes use of either phagemid, which is packaged with helper phages, or temperate phages inserted as prophages into the bacterial genome. These constructs displayed modest efficacy in reducing systemic bacterial load, eliminating bacteria from exposed surfaces, and topical treatment of bacterial skin infections in a mouse model. Embedding the CRISPR machinery in a phage-like pathogenicity island has also shown promising effort in blocking the event of subcutaneous or systemic Staphylococcus aureus infections by killing the bacteria or leaving them avirulent. 

The second dispersal approach makes use of conjugal transfer plasmids using type IV secretory systems (TSS4) to distribute CRISPR components to either Gram-negative Enterobacteriaceae or Gram-positive Enterococcus spp. determinants designed to obstruct the entry of the latest antibiotic-resistant factors (AR factors) into the agricultural environments.

Another potentially powerful drive-enabling tool has been derived from the discovery of RNA-guided transposon systems. If combined with other CRISPR tools, such as the pro-AG (Pro-active genetic) systems, the next-generation configurations of self-propagating elements might be developed to reduce AR prevalence in the environmental and clinical settings as Pro-AG systems target the genes in antibiotic-resistant bacteria, next-generation configurations of self-propagating elements might be developed to reduce AR prevalence in environmental and clinical settings.

Significance of the study

The reduction of antibiotic resistance (AR) is a complex and challenging problem that requires both societal and science-based solutions to preserve the most lifesaving pharmaceutical intervention that is known to medicine. It’s necessary to protect the clinical efficacy of existing drugs, in addition to developing new classes of antibiotics. This crisis can only be addressed by mutual efforts to develop strict new antibiotic management guidelines by the medical establishment; enacting laws to prohibit inappropriate agricultural practices, such as adding antibiotics in animal feed to enhance livestock growth; and robust partnerships between industry, philanthropies, and government agencies for the development of new natural or synthetic antibiotics, innovative immunotherapies, or novel antibacterial and anti-AR compounds to extend the endurance of existing antibiotics. The following significant conclusions could be drawn from the study in discussion:

(i) CRISPR-based technologies have demonstrated considerable promise as weapons in the recurring and escalating battle against multidrug-resistant bacterial infections. 

(ii) Phage and conjugative horizontal gene transfer vehicles can circulate the CRISPR anti-AR platforms throughout bacterial populations.

(iii)  Anti-AR CRISPR systems have the ability to reduce AR prevalence in experimental infection models. 

(iv) Self-amplifying proactive genetic systems enhance anti-AR efficacy approximately 100-fold. 

(v) Guide RNA–directed transposons should allow insertion of anti-AR CRISPR platforms into multiple defined genomic or episomal target sites.

Thus, the research in discussion holds great significance for the present as well as the future of medicine.

Also read: Increased Omega-3 consumption linked to cardio-protection

Source: Bier, Ethan, and Victor Nizet. “Driving to Safety: CRISPR-Based Genetic Approaches to Reducing Antibiotic Resistance.” Trends in Genetics, vol. 37, no. 8, Aug. 2021, pp. 745–57. www.cell.com, doi:http://10.1016/j.tig.2021.02.007

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About the Author: Husna is an undergraduate student of BTech Biotechnology at Amity University Kolkata. She is a research enthusiast in Immunology and Immunotherapy but she has a keen interest in various other Bioscience subjects as well. She is constantly focused on improving her knowledge and laboratory skills through various internships. She is a Scientific content writer who has knowledge in diverse backgrounds of Biotechnology.