Antimicrobial resistance (AMR) has been pegged as a significant threat to public health globally. It is making infectious diseases harder to treat, and in some cases, causing more deaths and illnesses. This also leads to higher healthcare costs for certain combinations of pathogens and drugs.
According to a study, in 2019, bacterial AMR was reported to directly cause 1.27 deaths while also contributing to an additional 4.95 million deaths.
That being said, in the face of this global crisis, biotechnology has emerged as a powerful tool to fight antimicrobial resistance pathogens.
In this article, we’ll explore the potentials of biotechnology in developing different antimicrobial resistance solutions.
What is AMR?
Antimicrobial resistance is the ability of pathogens (bacteria, viruses, fungi, parasites, etc.,) to grow and thrive in the presence of the antimicrobial agents developed to inhibit or exterminate them.
Genetic changes in pathogens over time can lead to AMR naturally. However, different factors and human activities act as catalysts to spur and accelerate it. The factors influencing microorganisms to get resistant to their antimicrobial agents include:
Natural Causes
Let’s go through the natural causes behind antimicrobial resistance.
Selective Pressure
Antimicrobial drugs, for example, antibiotics, are designed to kill the target microbe to control its population dynamics. However, if any of these microorganisms inherent a resistance gene, it remains unaffected, survives the antimicrobial treatment, and gets enough place to replicate and multiply.
This is how the progeny of these resistant microorganisms quickly becomes the dominant type throughout the population. The ability to survive treatment enables these resistant microbes to have a selective advantage over susceptible ones. Continuous consumption of the same drug can help resistant microbes thrive and increase their population dramatically.
Mutation
Mutation is a natural process that occurs when microbes replicate, causing alteration in the nucleic acid sequence of the genome of that microbe.
This genetic variability can result from errors during DNA replication or exposure to mutagens (radiation and chemicals). Since most pathogens have a high replication rate, they reproduce faster, resulting in a proliferation of mutations in their genome.
Some types of mutation can be beneficial to microbes implanting antimicrobial resistance properties into them.
When a specific antimicrobial drug is applied to target microbes with an AMR resistance-conferring mutation, the efan get deemed, or in some cases, are totally ineffective. The result is that the target microbe survives the treatment and spreads the resistant strains.
Gene Transfer
Genetic information can be transferred between two microorganisms that can disseminate the population of antimicrobial resistance-conferring pathogens.
As we have already stated, pathogens multiply in billions in a short time. It means that copies of genes encoding antimicrobial-resistant DNA can be spread out to billions of non-resistant microbes.
Thus, when the antimicrobial drug is applied, only the susceptible microbes get killed while the drug-resistant ones can reproduce even in the presence of drugs.
Now, let’s go through some human activities that may result in antimicrobial resistance in the human body.
Human-made Causes
- Overuse/Misuse of Antibiotics: Inappropriate use of antimicrobial drugs, such as overprescription or inadequate consumption, can exacerbate the selection of microbes. The Centers for Disease Control and Prevention (CDC) reported that during treatments, antibiotics are prescribed inappropriately roughly 30% to 50% of the time. Another study showed that around 30%-60% of drugs prescribed in intensive care units are highly unneeded, suboptimal or wrong.
- Limited Access to Clean Water and Proper Sanitation: It’s another leading cause that exacerbates antimicrobial resistance by helping infections spread and resistant pathogens spur. This is because unhygienic sanitation or environmental conditions can spur the growth, survival, and transmission of drug-resistant microbes.
- Limited Research on AMR: Lack of sufficient research to develop novel antimicrobials buoy AMR in pathogens. In addition, the slow pace of the development of effective AMR treatment increases the selective pressure for resistance, which helps resistant strains to survive and propagate even in an antimicrobial drug environment.
- Use in Agriculture: Overuse of antibiotics in agriculture can spur the penetration of antibiotics and antibiotic-resistant bacteria (ARB) in water and soil. Genetic elements like transposons and plasmids promote genetic evolution, and variability, further promoting antibiotic resistance genes within the pathogen population. All these factors – residues of antimicrobial drugs, integrated farming practices, accumulation of drug residues, etc.- play a key role in disseminating AMR and resistance genes (ARGs) in humans.
Biotechnology Solutions to Antimicrobial Resistance
Biotechnology, a fusion of “molecular biology” and “life science,” is a field of study that aims to help develop life-saving/improving therapeutics by manipulating microorganisms and living cells.
It has opened up new frontiers for facilitating the development of AMR solutions. Let’s go through some biotechnology solutions to AMR:
Genomic Analysis and Bioinformatics
One of the reasons behind AMR is the power of microbes to adapt and survive antimicrobial drugs through genomic changes. One of the key components of biotechnology, DNA sequencing, helps scientists decipher the entire genomic sequence of a pathogen. For example, next-gen sequencing (NGS), a type of DNA sequencing, comes with outstanding high-throughput capabilities to enable the rapid and parallel sequencing of large numbers of DNA fragments.
It helps determine low-frequency variants and genomic arrangements in microbial populations. Genomic analysis of an entire genome or a targeted part of a DNA helps experts identify the reason behind AMR. This knowledge helps modify existing drugs, and develop novel drugs and targeted therapies while also enabling them to implement surveillance programs to control the spread of resistant strains.
CRISPR-Cas9 Gene Editing
CRISPR-Cas9 Gene Editing has emerged as a powerful and targeted biotechnology tool to tackle AMR. It allows for selectively targeting and disabling virulence and resistance genes in a microbe. Thus, the microbe, once again, gets re-sensitised to existing antibiotics.
Phage Therapy
Phage, formerly called bacteriophage, is a type of bacterial virus that can selectively target and kill a bacteria strain.
Phages and their lytic proteins thus hold immense potential to tackle antibiotic-resistant pathogens. Phages therapy is thus a highly effective treatment that can be administered on the target infection through oral, intravenous, or topical applications.
CRISPR/CAS – a next-gen gene editing mechanism has revolutionised phage therapy. For example, phages altered biologically through CRISPR/Cas can be used to disrupt and kill antibiotic-resistant genes and plasmids. More research is yet to be conducted on bioengineered phages to harness their full potential in fighting off AMR.
Antimicrobial Peptides
Antimicrobial peptides are naturally derived small molecular peptides that show broad-spectrum activity against pathogenic microorganisms. These oligopeptides with low molecular weight are part of the innate immune system found among all classes of life and are now being commercially synthesised and modified using chemical synthesis or recombinant DNA technologies for their antibacterial properties.
In addition, the capability of selectively targeting a specific strain, including a drug resistance strain, can be used against invading pathogens.
Their cell-membrane permeabilisation activity is used here to make multi-drug resistant bacteria become sensitive to antibiotic agents again.
Furthermore, biotechnology processes can be used to modify the AMP sequences for stabler, enhanced, and specific therapeutic properties.
Vaccines and Immunotherapies
Different biotechnological processes such as recombinant DNA, viral vector technology, monoclonal antibody technology, messenger RNA (mRNA) technology, T-cell receptor engineering, etc., are widely used to produce vaccines and immunotherapies that target specific pathogenic organisms and prevent bacterial infection. It minimises the need for antibiotic intervention, thus preventing AMR.
Challenges in Biotechnology and Antimicrobial Resistance Solutions
With over 2.8 million cases of antimicrobial resistant (AMR) infections being reported annually in the USA alone, there is an increased focus on biotechnology to develop effective strategies for mitigating its impacts.
While biotechnology holds immense potential to battle AMR, it also comes with a slew of challenges. For example, researching, experimenting with and developing biotech solutions is a time-consuming and expensive process. This challenge is doubled down by the regulatory hurdles – once you develop a therapeutic, it needs to be approved by the regulatory authorities before being rolled out in the market.
However, different life science and biotechnology companies are frequently collaborating to pave the way for combatting this issue. For example, plazomicin, a broad spectrum aminoglycoside and parenterally administered antibiotic, was developed by a biotech company, Achaogen. This FDA approved drug has been identified as highly effective in treating infections caused by multi-drug resistant Enterobacteriaceae.
Wrapping Up with Future Prospects
Experts predict that biotechnology, in tandem with high-end technologies, such as machine learning, omics technology, etc., can accelerate research and development of highly effective therapeutics while expediting product-to-market.
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