Antibiotic Resistance - Causes, Prevention and CRISPER Technique
Authors: Batthini Sai Pranank

1) Introduction


The term antibiotics is derived from the Greek word “anti” means against and “biotikos” means is concerning life. There are many types of antibiotics such as antibacterial, antivirals, antifungals and anti-parasitic’s. Some drugs are effective against many organism; these are called broad-spectrum antibiotics. Others are effective against just few organism; these are called narrow-spectrum antibiotics. The most commonly used antibiotics are anti-bacteria’s. These are used to treat infection caused by bacteria and certain parasites ( Antibiotics eradicate bacterial infections by bacteriostatic or bactericidal effects (Briand 1978). Bactericidal drugs are those that kill target organisms. Example of bactericidal drugs includes aminoglycosides, cephalosporins, penicillins and quinolones. Bacteriostatic drugs inhibit or delay the bacterial growth and replication. Example of bacteriostatic drugs includes tetracyclines, sulfonamides and macrolides (

Antibiotic Resistance

The ability of bacteria and other microorganisms to resist the effects of an antibiotic to which they were once sensitive. Antibiotic resistance is a major concern of overuse of antibiotics. Also known as drug resistance. The indiscriminate use of antibiotics led to the emergence of antibiotic resistant bacteria that caused the treatment

complications. Nowadays, the problem of antibiotic resistance has become one of the biggest threats to global health, food security, and development (WHO 2016). A recent report from WHO revealed the pervasiveness of antibiotic resistance across many infectious agents, especially bacteria responsible for common serious diseases such as bloodstream infections (sepsis), diarrhea, pneumonia, urinary tract infections and gonorrhea [WHO, 2014]. WHO recently reported the widespread of resistance in E. coli to one of the most widely used medicines for the treatment of urinary tract infections (fluoroquinolone antibiotics). The ECDC (European Centre for Disease control and prevention) says that antibiotic resistance continues to be a serious public health threat worldwide. In a statement issued in November 2012, the ECDC reported an estimated death of 25,000 people each year in the European Union due to antibiotic-resistant bacterial infections.

2) Some causes of Antibiotic Resistance

  1. Overuse The rapid emergence of resistance resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics which have saved millions of lives. As early as 1945, sir Alexander Fleming raised the alarm regarding antibiotic overuse, when he warned that the “Public will demand (Drug), then will begin the era of Abuse”. The overuse of antibiotics will clearly drives the resistance of bacteria. Epidemiological studies have demonstrated a direct relationship between antibiotic consumption and the emergence and dissemination of resistant bacteria strains. In bacteria the gene transfer can be done through various mobile elements. For an Ex. Horizontal gene transfer can be used to transfer gene from one species to another. The number of antibiotic prescriptions varies by state, with the most written in states running from the Great Lakes down to the Gulf Coast, whereas the West Coast has the lowest use
  1. Inappropriate Prescribing Incorrectly prescribing antibiotics will also lead to the “Resistance”. Studies have showed that, 30% to 50% cases of antibiotic resistance were due to incorrect prescribing. Incorrectly prescribed antibiotics have questionable therapeutic benefit and expose patients to potential complications of antibiotic therapy. Inappropriate prescribing can promote the development of antibiotic resistance by supporting genetic alterations, such as changes in gene expression, HGT, and mutagenesis.
  2. Extensively used in the Animal Husbandry and Agriculture Animals are treated with antibiotics and they can therefore carry antibiotic resistant bacteria with them. Eventually vegetables are contaminated with this antibiotic resistant bacteria from animal manure used as fertilizers. Antibiotic Resistant bacteria can spread to humans through food and direct contact with animals.
  3. Environmental Factors Natural disasters or calamities like earthquack, tsunami, or political situations like civil war where the medical conditions are heavily weakened can also lead to the high case fatality rates due to the thriving Drug resistant bacteria. Many drugs such as antibiotics, antidepressants, chemotherapeutics and their residues often escape purification by water treatment plants and, therefore, contaminate drinking water supplies. Considerable amounts of these antibiotics are released into the biosphere by hospitals, research laboratories, pharmaceutical industries and domestic use. It is not surprising that the microbial world in soil, water and food has to resort to myriad resistance determinants to avert the catastrophe due to these contaminants

3) Strategies to Minimize Antibiotic Resistance

Antibiotics have been greatly important keystone of Clinical Medicine since mid-20th century and have saved millions of people from life-threatening disease. But, 21st century have witnessed for the development of antibiotic resistant agents. The gradual increase in resistance rates of several important pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), multidrug-resistant (MDR)Pseudomonas aeruginosa, imipenem-resistant Acinetobacter baumannii, and third-generation cephalosporin-resistant Escherichia coli and Klebsiella pneumonia, poses a serious threat to public health (Chang-Ro Lee 1,†, Ill Hwan Cho 2,3, Byeong Chul Jeong 1 and Sang Hee Lee “Strategies to Minimize Antibiotic Resistance” International Journal of Environmental Research and Public Health, Public Health 2013).

  1. Appropriate Antibiotic Prescribing Since the resistance to the first commercial antimicrobial agent (penicillin) was identified in 1948, almost every known bacterial pathogen has developed resistance to one or more antibiotics in clinical use. As antibiotic-resistant pathogens are observed almost concurrently with the use of new antibiotics in hospitals, one can easily suppose that wherever antibiotics are used, antibiotic resistance will inevitably follow. Unfortunately, although antibiotic resistance has increased, the development of novel antimicrobial agents has dramatically declined over the past 30 years. Therefore, to prevent the return of the pre-antibiotic era, one must use existing antibiotics more judiciously. Proper Knowledge of Disease and Antibiotics should be there.
  2. Antimicrobial Awareness Program Various awareness program should be carried out for creating awareness of this major problem in the society. Many institutions conduct Antimicrobial Stewardship Programs (ASPs) to optimize antimicrobial therapy, reduce treatment-related cost, improve clinical outcomes and safety, and reduce or stabilize antimicrobial resistance. Typically, ASPs are executed by multidisciplinary antimicrobial utilization teams comprising physicians, pharmacists, microbiologists, epidemiologists and infectious disease specialists, with adequate experience in their respective fields.
  3. Hygiene and Disinfection Resistant Pathogen can easily survive where there is lack of hygiene and often causes hospital infections. In the United States (U.S.), 1.7 million hospital-acquired infections are recorded each year, which result in about a hundred thousand deaths (WHO). Therefore, appropriate hospital disinfection and personal hygiene of healthcare workers are required to prevent hospital-acquired infections.
  4. Development of Novel Antibiotics Antimicrobial drugs such as antibiotics are a unique class of drugs that does not directly target human biochemical processes but instead affect the growth of invading pathogens and commensal microbiota. Bacteria can easily adapt to their environmental changes and decrease their susceptibility to antibiotics by several mechanisms, including mutation and horizontal gene transfer within and between species. Therefore, new weapons are always indispensable for combating bacterial infections. Nevertheless, most of the antibiotic classes being used today were discovered during the period 1930–1960. Besides, during the past 30 years, only two new systemic classes of antibiotics (oxazolidinones in 2000 and cyclic lipopeptides in 2003) and two topical classes (pseudomonic acids in 1985 and pleuromutilins in 2007) were introduced in the market

4) Presented Work

Even since Alexander Fleming stumbled across penicillin—the first antibiotic drug—scientists knew our fight with evolution was on ( Most antibiotics work by blocking biological processes that allow bacteria to thrive and multiply. With prolonged, low-dosage use, however, antibiotics become a source of pressure that forces bacteria to evolve—and because these microorganisms are extremely adept at swapping and sharing bits of their DNA, when one member becomes resistant, so does most of its population. Even more terrifying is this: because the same family of antibiotics generally act on the same biological pathways, when bacteria generate a mutation that resists one type of drug, it often renders that entire family of drugs useless. The arms race with increasing high rates of antibiotic resistance has forced scientists to think outside the box. Although still a work in progress, teams of scientists are now working on a truly creative strategy: a pill carrying the genome-editing power tool CRISPR that instructs harmful bacteria to shred their own genes to bits.

CRISPER Technique to prevent Antibiotic Resistance (CRISPER Antibiotic)

CRISPER is the abbreviation of Clustered Regularly Interspaced Short Palindromic Repeats. In essence, scientists are returning CRISPR to its roots. While best known as a handy way to manipulate DNA in mice and humans, CRISPR is actually a part of the bacteria’s immune defense system. Just like our immune systems can turn against ourselves, scientists are now hoping to give harmful bacteria a destructive autoimmune disease. When optimized, a CRISPR pill could have the ability to precisely target single strains of harmful bacteria, while leaving other types—including beneficial bacteria in the gut—intact.

The slow and obsolete

We are rapidly losing our war on microbugs, and if things don’t change we’re heading full throttle into an antibiotic apocalypse. Part of the bacteria’s survival prowess comes from their ability to rapidly multiply. Under the right conditions—a damp, nutrition-packed human cell, for example—the common gut bug E. Coli multiplies exponentially, doubling every thirty minutes. This gives their DNA plenty of chances to mutate and for the species to adapt. What’s more, bacteria aren’t stingy about sharing their DNA. Antibiotic-resistant genes are often carried on snippets of genetic material that floats around in the bacteria’s innards. Microbugs can literally extend a tube out to their neighbors to inject these genetic pieces, thus sharing their resistant genes far and wide. Most of our current antibiotics work in one of few ways: interfering with the bacteria’s DNA repair system, stopping the bacteria’s ability to reproduce, or weakening the bacteria’s cell wall—something our cells don’t have—until it explodes.

The new CRISPR pill eschews all traditional ideas, instead relying on the bacteria’s mortal enemy: a type of virus called bacteriophages (or, more endearingly, “phages”). Like all viruses, phages can’t reproduce on their own. Instead, they constantly invade bacteria and inject viral genomes into the hosts, hoping to co-opt bacterial machinery to make armies of phage replicas.

This onslaught of foreign genetic material has spurred bacteria into developing a sophisticated defense system. When bacteria detect viral DNA, they store bits and pieces of it into their own genome to form a genetic sequence that we call CRISPR—a molecular “memory” of the phage, so to speak.

When the bacteria detect a matching viral DNA sequence, they activate CRISPR and, together with a pair of protein scissors called Cas-9, the system destroys the viral DNA. Voila, invasion blocked.

CRISPR antibiotics

Scientists have found that the CRISPR system doesn’t cut the bacteria’s own DNA under normal circumstances; when it does, the result is lethal. This spurred an ingenious idea: scientists could use phages to inject custom Trojan horses that trick the bacteria into cutting its own genes. Bacteria cells without the resistant gene didn’t sound their alarm bells, and in turn were spared and ended up dominating the population. C. diff is an infection that is notoriously difficult to treat, causing long-term gastrointestinal distress in nearly half a million Americans in a single year, resulting in at least 15,000 deaths. The current best treatment—when antibiotics fail—is a faecal transplant from healthy donors, but the method is still considered experimental, and long-term effects are unclear.

5) Conclusion

With the advancement of technology in health care system, the more number of resistant strains are produced. There will be a situation where, new and novel antibiotics won’t be made due to solemn multifaceted resistant bacteria. The possible way to reduce this resistance is by using some techniques, which will eventually attack on bacteria itself.

About Author / Additional Info:
Student of Biotechnology. An Enthusiast in finding new things.