UConn scientists have engineered antibiotics that target MRSA, a deadly bacterium that causes skin, lung, and heart infections. Their success lies in the technique they utilized that makes it difficult for the bacteria to counteract. the research was published in the 22nd December issue of Cell Chemical Biology.
MRSA, which stands for Methicillin-Resistant Staphylococcus Aureus, are increasing and many patients have shown resistance to common antibiotics. trimethoprim-sulfamethoxazole which is a relatively safe and cheap solution to MRSA, but many patients have become resistant to trimethoprim-sulfamethoxazole, and resistance is spreading across the globe.
Up to 30% of sub-Saharan population infected by the condition, does not respond to the treatment, and the number is increasing in many Asian and European countries as well.
UConn chemical scientists Dennis Wright, Amy Anderson and Ph.D. student Stephanie Reeve have been developing a drug that will be difficult for MRSA to form resistance against.
The scientists had different candidates in the making when they asked colleagues at UConn Health and Hartford Hospital to start extracting trimethoprim-resistant strains of MRSA as test cases.
Dr. Michael Nailor, a UConn pharmacologist co-funded with Hartford Hospital had this to say,” Although resistance [to trimethoprim] in the community is generally less than 10% in our local area, resistance elsewhere is climbing. Additionally, many vulnerable patient populations cannot take trimethoprim-sulfamethoxazole or other generic drugs because of side effects they may cause, and new agents are needed.”
The samples they observed, showed how rapidly the bacterial resistance was spreading. Six of the nine bacterial strains extracted had trimethoprim resistance genes that were never previously identified in the US.
The strains were also resistant to several other antibiotics such as erythromycin and tetracycline, which are common antibiotics prescribed by doctors.
But the samples were no match for the bioengineered antibiotics that the scientists had developed in their lab. Stephanie Reeve remarked that their strategy had worked and was happy to know that their antibiotic performed great.
Wright further added, “One of the most exciting aspect of this work was that we had worked hard to design broadly acting inhibitors against many different resistant forms of the enzymes and these designs proved very effective against two new enzymes we had never considered or previously studied.”
The strategy, the scientists adopted, was to hit the bacteria’s utilization of Vitamin B9. Also known as folate, b9 is as essential to MRSA bacteria as it is to humans. If the vitamin’s effects are blocked off, then a vital enzyme’s essential express is turned off and the bacteria die.
Trimethoprim is currently the only antibacterial antifolate available, the biggest shortcoming of this is that bacteria have developed different versions of the folate enzyme that are not affected by it.
Though Anderson, Wright and Reeve believed they should be able to develop other, more improved antifolates, to counter the antibiotic resistance. They carefully analyzed the molecular structure of the enzyme they were trying to study, and tried to figure out how it needed to interact with other molecules to perform correctly.
According to Wright, only by comprehending its purpose, shape and functionality could they understand versions of the enzyme they’d never observed before.
After gaining much knowledge, and utilizing their researched the scientists designed new antifolates. These drugs are engineered to bind the enzyme in such a way that if the enzyme changes enough to elude them, it won’t be sufficient enough to do its job properly with vitamin B9, either. That will hopefully make it difficult for bacteria to invoke antibiotic resistance. The drugs’ success against the trimethoprim-resistant strains of MRSA sampled so far bodes well.
Most MRSA infections originate in hospitals and clinic settings. MRSA infections occur due to invasive procedures or devices, such as surgeries, intravenous tubing or artificial joints. MRSA infections start out as painful boils and can spread through skin contact.
Since they start as painful red bumps, over time they may spread out to form painful abscesses, and therefore can require surgical draining. But in many cases, the bacteria aren’t completely removed and can stay in the skin, and may even penetrate deep below to other organs causing potentially life-threatening infections in bones, joints, flow into the bloodstream, and reach heart valves and lungs.
Bacteria develop antibiotic resistance in two ways. Many acquire mutations in their own genomes that allow them to withstand antibiotics, although that ability can’t be shared with pathogens outside their own family. The other way is when the superbug reproduces by manipulating plasmids.
Microorganisms develop resistance when they replicate and exchange genes in between them. However, prescribing antibiotics for the smallest of infections and over-prescriptions by many medical professionals over the years may also have been a reason for microorganisms to develop such hard resistance.
The Centers for Disease Control and Prevention (CDC) has estimated more than 2 million people contract infections from pathogens with antimicrobial resistance, which leads to more than 23,000 deaths every year.
Although antibiotics are also one of the most prescribed drugs used for lifesaving conditions in the US, 50% of the time the drugs are given to patients unnecessarily.
Antimicrobial resistance can be developed in microorganisms such as bacteria, fungi, virus, parasites and all microbes which are pathogenic in nature.
Even common infections like flu, pneumonia, urinary tract infections etc. can become lethal. Other infections of increasing concern all over the world are caused by bacteria such as Methicillin-Resistant Staphylococcus Aureus (MRSA) or multidrug-resistant Gram-negative bacteria.
Given the high-risk factor of getting infected, proper measures are needed and quick. There have been numerous efforts by several government agencies.
The National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS) is working to keep an eye on the changes in the antimicrobial susceptibility of certain enteric (intestinal) bacteria found in ill people, retail meats and food animals in the United States.
Fortunately for us, if similar medical breakthroughs continue, antimicrobial resistance will be a thing of the past. Genetic engineering and latest analysis tools to monitor the physical characteristics and genetic expressions will play a vital role in the key to fight antibiotic resistance. Therefore, the next few years will be crucial in this fight.