• Jonathan Kabiito

Microbes, Man & the Zoonotic Spillover

Updated: May 9, 2021

We spoke to Maureen Chinwendu Onyeziri, a microbiologist ,Ph.D. Candidate at Indiana University Bloomington and currently a Crop Genome Engineering Intern at Corteva Agriscience on Microbes, Man & The Zoonotic Spillover

Perhaps the most important biomedical discovery around man's coalition with microorganisms is the phenomenon of the microbiome; the fact that there are various communities of good bacteria which occupy specific parts of our bodies and form an inseparable functional unit with us: gut bacteria, for instance, help us with digestion. How have the rapid mutations in the microbial world affected this coalition?

Rapid mutations in microorganisms tend to have small or large effects depending on what genes are mutated, and our microbiomes are not left out. In our gut for instance, where there are several different species of microorganisms that live and function, there is constant and extensive genetic recombination occurring among these organisms. Consequences of this phenomenon include changes in the way these organisms extract nutrients, evade antibiotics, or interact with our immune systems.

Almost like the human genome, studies have shown a diversity in human microbiome across populations, and their roles in health. Do you think there is some kind of correlation between genetic diversity and the diversity in microbiota?

Yes. Studies have shown that vaginal, gut, skin and oral microbiomes differ among different races and ethnicities, with specific races or ethnicities having certain microorganisms dominate their microbiomes compared to others. Now, you have to understand that we humans are not as genetically diverse as we like to think. In fact, human genomes are 99.9% the same among any two people regardless of race. However, seeing as there are marked differences in our microbiomes based on race and ethnicity, it suggests that something in our 0.1% genetic variation also influences our microbial composition.

The mechanisms of action of most antimicrobials often mean that both the good bacteria in the human microbiome and the target pathogenic ones are affected. How do we manage the effect and what implications might this hold for human health?

Unfortunately, you are correct. Many of our antimicrobial drugs are able to cause harm to our “good” bacteria even as they target the “bad” ones. This is why medicine in combination with a good diet are essential in ensuring that the body bounces back from illness. Some people advise taking probiotics to quickly replenish the diminished microbiota following a rigorous course of antibiotic treatment, but more and more scientists are looking into “smart” antibiotics: antibiotics that essentially kill the bad bacteria while sparing the good ones. Obviously, this targeted approach will require drugs that deviate from the more common modes of action of our regular antibiotics, and work to silence genes specific to the “bad” bacteria only. This is still an active area of study, but will have tremendous positive implications in how we currently manage infections.

Antimicrobial resistance has been declared a global public health crisis. This, of course, is due to the emergence of resistant strains of microbes. Experts fear that we may never be able to race microbes to it by developing new antibiotics. What do you think we should be doing differently?

We are already starting to do things differently with combination therapy to deal with increasing antimicrobial resistance. However, it is only a matter of time before “super bugs” that are resistant to various antimicrobial combinations become a beast too large to control. Scientists are starting to look at alternatives to antibiotics that include utilizing antibodies, outcompeting the pathogen with the body’s good bacteria (using probiotics), smart antibiotics as I’ve mentioned before that target specific genes instead of general metabolic and synthesis pathways, and utilizing bacteriophages to attack the pathogen. These are all in the pipeline as future alternatives to antibiotic use.

Do you think antimicrobials should be regulated in some way to check abuse?

In developed countries, antimicrobials are already pretty heavily regulated. For one, you cannot simply walk into a pharmacy and get them over the counter. You need a doctor’s prescription. And you are only sold the exact dosage stipulated in that prescription. If you complete the dosage and symptoms persist, another doctor’s visit to get a new prescription or to authorize a refill of the old one is necessary. In developing countries, the situation is very different, self-medication is rampant and with that comes drug abuse. It is easy to walk into a pharmacy, “chemist” shop or even a road-side kiosk to buy antibiotics that should normally only be sold with a doctor’s prescription and certainly not in street kiosks by semi-illiterate traders. I would say more regulation is needed in developing countries to combat antimicrobial resistance.

Genetic modification has played important roles in the improvement of food security and healthcare. What regulations are in place to check the horizontal transfer of traits from genetically modified microbes used in these industrial processes into unmodified ones in our natural environment?

The short answer: A ton. Contrary to what a lot of people think, there are myriad regulations in place to ensure the safety of so-called GMO products, and companies who produce GMO goods make sure that their products go through rigorous testing at each stage of the production pipeline before they hit the market. Even after internal testing, these goods are typically subjected to another round of testing by government agencies such as the U.S. Food and Drug Administration (FDA). And even after this, there are policies in place that restrict unmonitored selling of GMO products in many countries. So, it is a hassle and companies in the business have to jump a lot of hoops just to get their products into the market.

The disruption of ecological balance has been cited as the major cause of most of the diseases we battle today, as microbes cross the species lines from displaced tropical animals to ours. How do you think we can manage the situation?

Simple, stop encroaching on natural habitat. Industrialization has seen us encroach more and more into our natural spaces that should otherwise be left untouched thereby disrupting ecological balance and increasing our proximity to wild animals that are reservoirs for many pathogens. Of course, simply saying we need to stop altering natural environments is wishful thinking since there are often socioeconomic and political factors involved. In the end, it will require a concerted global effort to manage the situation.

Efforts to create some kind of biological alarm systems to help predict hotspots for Emerging Infectious Diseases meet with the problem of parameters. Do you think there are parameters in microbial behaviour scientists can use as metrics in the development of predictive models?

Not really. Microbial behavior can change very quickly as these microbes adapt to swiftly changing environmental conditions. They are also small enough and replicate fast enough that adaptation, jumping, and spread can happen in a short time, way before we know what is going on. And if we aren’t monitoring for these adaptations to begin with (because we don’t know what they are or how they will occur), then it will be very hard to create the kind of alarm system that will allow us accurately predict emergence of new diseases.

Nonetheless, there are many things we can do once we identify a potential outbreak that can eliminate the lengthy delay in information transmission between the multi-level public health infrastructure we currently have in place globally. It is this delay that often stalls epidemiological surveillance with occasional catastrophic results. I believe that improving our current investigative infrastructure and improving our control strategies will help us tackle emerging infectious diseases better. This does not mean that modeling shouldn’t be part of an epidemic or pandemic emergency response. It is just very daunting, and not always as clear cut, as the 2009 H1N1 pandemic proved.

Do you think things will ever go back to the way they used to be?

Time never really moves backward, and nothing really goes back to the way it was. The world (including those of us in it) are always in a state of flux. Regarding the current pandemic, I do not think things will go back to what they used to be. If anything, this pandemic continues to teach us lessons about how we live and how our actions affect our planet that I hope we learn and implement moving forward. If we do, then our world will be nothing like it was pre-covid19.

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