BTEC 1322 (19190) Homework 1: CRISPR-Cas Technology Summary Analysis

This homework assignment summarizes the CRISPR-Cas system's biological function in microbes and its use in treating antimicrobial-resistant pathogens. The summary includes the background of antibiotic resistance, the advantages of CRISPR-Cas, such as its ability to guard host genomes and regulate bacterial functions, and its disadvantages, like packaging and delivery challenges. The impact of CRISPR-Cas on bacterial pathogenicity and the immune response is discussed, highlighting its role in regulating virulence. The conclusion emphasizes the importance of CRISPR-Cas in combating antimicrobial resistance, with examples of its application in creating resistant pathogens. The assignment is based on the review article by Shabbir et al. (2019), covering the CRISPR-Cas system's potential in addressing the global health concern of AMR pathogens.

Biotechnology
Background
Over the years, modern medicine has dramatically gained a lot of influence from antibiotic compounds.
Antibiotics can shield against many infections. However, their careless use in agriculture and veterinary
poses a significant environmental threat. Exposure to a variety of antibiotics in the environment causes
antimicrobial resistant genes in bacteria and selectivity (1). Antimicrobial resistance is still a threat
today. The resistance of these genes makes it possible for bacteria to defeat antibiotics through the
deactivation of bacterial enzymes, efflux pump, and chemical modification to shield the target cells (2;
4). In light of these mechanisms of resistance, the efficiency of antibodies comes under threat. CDC
approximates that by 20150, drug resistance will have caused 10 million fatalities. Drug resistance,
therefore, is facilitated by the ability of the bacteria to assume genotypic and phenotypic heterogeneity
in harsh environments.
Advantages
CRISPR-cas system guards host genomes against external invaders to maintain genetic balance. If
allowed into the genome, foreign materials might bring with them foreign genetic genes which might
end up being beneficial by enhancing bacterial resistance and fitness (3). Besides, it is also important to
note that the CRISPR-cas system regulates BLB, thus promoting envelop integrity of F. novicida.
Ultimately, resistance against specific membrane stressors is developed (3). Bacteria with CRISPR-cas
system have a higher ability capacity for resistance and fitness against bacteria.
Disadvantages
CRISPR-cas9 easily adapts to and can be programmed to alter RNA sequences. However, the methods
used to engulf sgRNS and protein lower their use because of their low packaging and loading
efficiencies. Besides, the need for more dosage increases its toxicity (4). Another major disadvantage
facing CRISPR-cas system is the complexity of the CRISPR-cas9 antimicrobial delivery systems (4; 2).
Delivering this complex substance into Gram-positive and Gram-negative bacteria is a significant
challenge. Using CRISPR-cas9 against non-laboratory resistance substances has been a significant
obstacle.
Impact
CRISPR-cas system has played a significant role in the regulation of bacterial pathogenicity as well as the
endogenous transcription of bacteria. For instance, when Francisella novicida bypasses the host immune
system and replicates, the body responds. However, several mechanisms can be used to defeat the
disease-causing agent. For instance, the presence of TLR2 detects bacterial lipoproteins (3). Ultimately,
the activation of TLR2 triggers pro-inflammatory immune responses that eventually destroy the bacterial
pathogen (3). Cas9 has significant inflammatory reactions and thus is suitable for the elimination of
bacteria. Therefore, the CRISPR-cas system is an excellent regulator of virulence by suppressing their
activities in the body of the host.
Conclusion
It is undeniable that the AMR pathogens have posed a global health concern. Of the many strategies
deployed to mitigate the development and use of AMR, new technology in the CRISPR-cas system has

been instrumental in fighting resistance against pathogens. Using the CRISPR-cas system, researchers
have succeeded in creating inter and extracellular resistant pathogens such as the MRSA infection and B.
pseudomallei pathogens, respectively. Regardless, applying CRISPR-cas9 antibacterial on pathogens in
the laboratory which are non-resistant remains a big challenge.

References
1. Kümmerer K. Signifcance of antibiotics in the environment. J Antimicrob Chemother. 2003;
52:5–7.
2. Wright GD. The antibiotic resistome: the nexus of chemical and genetic diversity. Nat Rev
Microbiol. 2007; 5: 175.
3. Jones CL, Sampson TR, Nakaya HI, Pulendran B, Weiss DS. Repression of bacterial lipoprotein
production by Francisella novicida facilitates evasion of innate immune recognition. Cell
Microbiol. 2012; 14: 1531–43.
4. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA—
guided DNA endonuclease in adaptive bacterial immunity. Science (80−). 2012; 337: 816–21.