The Threat of Antimicrobial Resistance

“Opportunistic” Bacteria and the Role of Antibiotics
Despite their importance, some bacteria can also make us sick. Bacteria like E. coli are found naturally as part of a healthy intestinal tract in humans and animals, we well as in the environment. Unfortunately, some strains of this bacteria can cause foodborne illness and are periodically responsible for the recall of products like ground beef, onions, and spinach. Other bacteria are only known to cause disease, with no known commensal benefits. An example of this is Yersinia pestis, which in humans is always going to cause plague, a potentially life-threatening disease that has been the cause of several major epidemics the past few thousand years. Another pathogenic species, Bacillus anthracis, causes anthrax, which can also be dangerous or life-threatening when humans come into contact with it.  

In other situations, there are bacteria that are what we call “opportunistic.” These are often present on our skin or in our body, but they only become a problem in certain situations like when our immune systems are compromised or if they gain access to a different part of our body, like through a cut in our skin. They take advantage under the right (or if you’re the impacted individual, wrong) circumstances. These can include Clostridioides difficile (formerly called clostridium difficile), which is typically found in everyone’s gut. Under the wrong conditions when other “good” bacteria are depleted, it can become overabundant and cause diseases like irritable bowel syndrome and other terrible symptoms.  

As a result of these opportunistic and potentially harmful bacteria, there is sometimes the need to remove them for our own health and safety. This can be done by using products like bleach, isopropyl alcohol, or hydrogen peroxide. These are sterilizing chemicals, and they do a great job at killing off all the microbes present where they’re applied. However, these chemicals are also quite toxic, and we can’t apply them in certain scenarios, like for instance, inside the human body. In those cases, we use selective chemicals called antibiotics. These compounds are designed to specifically target the bad bacterium acutely impacting our health while not hurting their host, whether human or animal, though they can also kill off the good bacteria in the body.   

The Issue of Antimicrobial Resistance
The issue presents when resistance to these antibiotics, antivirals, antifungals, and antiparasitics develops, which is called antimicrobial resistance, or AMR for short. At MRIGlobal, a portion of our work is focused on antimicrobial resistance to bacteria, addressing this problem as it relates to Mycobacterium tuberculosis (Mtb), specifically, which is the causative agent of tuberculosis. In Mtb and other pathogenic bacteria, there is concern that today’s antibiotics will no longer be effective against their bacterial targets in the future, based on mutations in a minority of cases. If these cases became a majority of bacterial infections, this could potentially upend our day-to-day lives as we know them and have really dire healthcare consequences. Things such as scratches, surgeries, and organ transplantation would suddenly present greater risk than they do with our current antibiotic safety net. Read about a current outbreak of tuberculosis in the United States and why it prompts concern for antimicrobial resistance at “Should I Be Concerned About Tuberculosis?”. 

AMR is a consequence of human actions, and as such, it is something that can be overcome through action. Typically, we cite the misuse and overuse of antibiotics as being responsible for driving antimicrobial resistance. This can be due to not finishing a prescribed treatment of antibiotics for the full course according to your doctor’s instructions, which results in not killing all the targeted bacteria, leaving some to survive to develop resistance to the antibiotic they encountered. It can also be due to the use of antibiotics in farming that we rely on to keep animals healthy and disease free. As a result, some diseases are now requiring a multi-drug regimen to try and combat them, which is what we see in our work with Mtb. Read more about how to address antimicrobial resistance through use of a multi-drug regimen at “Battling Antimicrobial Resistance.”  

MRIGlobal’s Work to Support Improved Diagnostics
Clinicians rely on diagnostic tests to assess the antibiotic susceptibility of a patient’s disease. The results provide the necessary information to determine which antibiotics to prescribe in the treatment of that patient’s individual case. MRIGlobal works on this in two main ways:  

1. We perform research and development with diagnostic companies to make their diagnostics more accurate, informative, quicker, and easier to use. Sometimes these products are very rapid diagnostics that can provide partial resistance information to what we call “first line drugs” in under two hours. To go from sample to disease detection and AMR determination that quickly has been an incredibly important development in fighting tuberculosis and antibiotic resistance. Because these diagnostics must be accurate, it is very important that we do our job well. For instance, there’s an outbreak on the other side of the world right now, where the use of a single rapid test that is incorrectly diagnosing antibiotic resistance is resulting in the persistence of a TB resistance strain that is now spreading widely throughout a subpopulation. In this case, there needs to be an update to this diagnostic test, or an accessory test deployed to detect this particular strain so it can be addressed.
2. In those cases where a rapid test cannot identify the resistance, clinicians typically perform antibiotic susceptibility testing by growing the patient’s specimen in the presence of different antibiotics to see what is effective and what isn’t. Unfortunately, this can often take 2-3 weeks to perform, and patients must wait while this occurs. More and more, clinicians are turning to genetic analysis of a patient’s disease to get antibiotic susceptibility results in 2-3 days or less. At MRIGlobal, we study and perform full genetic sequencing of TB isolates, comparing the bacteria’s genetic sequence against what we see when we grow that isolate in a culture that contains antibiotics at different concentrations. This is akin to a “know your enemy” approach. By knowing the genotype, which is the genetic sequence, and linking that to the phenotype, which is how the bacteria actually grow or don’t grow in the presence of antibiotics, we contribute to a growing body of work linking genotype to phenotype to make rapid diagnostics more accurate. In this case, we could sequence that strain that is evading detection by the rapid diagnostic to know what particular mutation is causing that outbreak and then adjust either the original diagnostic assay or add a second test to cast a wider net. Sequencing data from diverse, global strains is being compiled by researchers to create a comprehensive list of mutations in the TB genome, which are known to cause resistance in patients. That information can be used to create better diagnostics. 

Holding Out Hope
It’s safe to assume that AMR is going to continue its impact on diseases like TB and may even get worse. By supporting public awareness and education about the problem, including the importance of finishing antibiotic prescriptions and not using antibacterial hand soap when it’s unnecessary, we can each take steps in the right direction. Ultimately, we’re also going to need broader changes, including new and better antibiotics, as well as systems to limit their immediate use in human and animal care. Longer term, new vaccine development to address current AMR pathogens will go far toward making sure that we have these vital antibiotics when we really need them. And that’s reason for hope.