Erin Merritt
There are potentially billions of different types of bacteria, and they’re found almost everywhere. Some are friends while others are foes. Kitchen sponges? Studies show that they contain 45 billion bacteria per square centimeter.
Another study suggests that your desktop has 400 times more bacteria than your toilet seat. And did you know that the average belly button is home to 67 different types of bacteria? For the few microbes that have the potential to make you sick, you can try to kill them with an antimicrobial cleaner or soap, or an antibiotic. But those that survive, they may actually become stronger.
Ryan Howard is a senior scientist working to detect pathogens and link genetic mutations and bacteria to antimicrobial resistance to improve diagnostic tests and ultimately help clinicians provide better care. On this episode, antimicrobial resistance, the threat it presents, why it’s becoming more of a problem and why there is reason for hope.
I’m Erin Merritt and this is Science Diction from MRIGlobal.
Ryan Howard
At the outset here, I think it’s important to mention that bacteria are incredibly important to the complex environment we’re a part of, and that without bacteria, we’d be in a lot of trouble. From aiding your digestion to nitrogen fixation, bacteria are really important.
Erin Merritt
What’s the most interesting thing about bacteria?
Ryan Howard
So to me, I think what’s interesting is that we can’t really live without bacteria despite all our efforts otherwise. And the reputation that bacteria may be unfairly had amongst the general public.
Among many, many benefits, bacteria aid in digestion, destroy disease causing cells, break down waste products, and even actually prevent against infection.
Erin Merritt
So how many bacteria are out there?
Ryan Howard
So this turns out to be a very simple question with a lot of different really complex answers, most of which are back of the envelope with pretty sizable error bars. In terms of biomass, it’s estimated there are approximately 70 gigatons of carbon worth of bacteria on planet Earth.
That’s 70 billion tons of carbon, and the scientists chose to use those units because it’s independent of water mass, and also those units are used to compare with other types of life on Earth such as plants.
Another way to think about the sheer number of bacteria is to be a little more introspective. For instance, dental plaque is so dense that it’s estimated that a mere one gram of plaque, maybe a little more than what might be removed at your next teeth cleaning, contains approximately a hundred billion total bacteria, which is roughly… the same number of humans to have ever lived, and that includes more than a thousand unique species of bacteria as well.
Erin Merritt
So in brief, there are a lot of bacteria out there, many of which haven’t been discovered.
Ryan Howard
Yeah. So while we have a pretty good sense of bacteria in our mouths or on our kitchen countertop, there’s an untold number of bacteria, mostly species we’ve never encountered or are currently unable to culture in a lab that are in the sediment of the ocean floor or living deep below the surface of the earth, where here deep below is greater than eight meters below the surface and doesn’t include soil.
These “deep subsurface” bacteria are estimated to make up the large majority of all the bacteria on planet Earth.
Erin Merritt
And then how many of these bacteria actually have the potential to make us sick?
Ryan Howard
This also turns out to be a simple question with a tough answer.
There are a number of bacteria that make us sick, and we recognize that they’ll always make us sick, and therefore we work to make sure that they don’t have the opportunity to do so.
For instance, bacteria like yersinia pestis or bacillus anthracis are always going to cause plague or anthrax respectively, and there isn’t much ambiguity in the literature there. However, in other situations, there’s bacteria that are what we call opportunistic.
That is they’re 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.
Erin Merritt
And how many of those bacteria are there?
Ryan Howard
So with those, it’s hard to truly get a count because the answer is there’s a lot of bacteria that can get you sick under the right or wrong circumstances.
For instance, clostridium difficile is typically found in everyone’s gut, but under the wrong conditions when other “good” bacteria are diminished, c-diff can become too over abundant and cause diseases like irritable bowel syndrome and a lot of other really terrible symptoms in people’s guts.
Erin Merritt
What happens when we try to kill them?
Ryan Howard
We often need to remove bacteria from places for our own safety. We do this using things 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 really toxic and we can’t apply them in certain scenarios, like for instance, inside the human body. In those cases, we really use selective chemicals called antibiotics.
These compounds are designed to target only a very specific part of a bacterium while not hurting their human host. That’s kind of the magic of antibiotics. You can ingest them and they won’t kill you while also killing off the… bacteria that’s in, for instance, your gut or your lungs.
Erin Merritt
Antibiotics are pretty incredible. So where’s the issue?
Ryan Howard
Well, the issue comes when we develop resistance to these antibiotics, which we call antimicrobial resistance or AMR for short.
Erin Merritt
What is the threat with antimicrobial resistance?
Ryan Howard
Antimicrobial resistance refers to resistance to antibiotics, antivirals, antifungals, and antiparasitics. My work focuses on antibiotic resistance and bacteria, and so this conversation will be biased towards resistance that occurs in bacteria.
When we talk about AMR, we’re talking about both the present as well as drawing a straight line towards the future based on what we’re seeing today.
Ultimately, we’re worried about scenarios where our antibiotics are no longer effective against their bacterial targets. On a broad enough scale, this would 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 be a lot more risky than they currently are with our antibiotic safety net.
Erin Merritt
And why is this becoming more of a problem today?
Ryan Howard
AMR is a consequence of human actions, and as such, it’s something that can be overcome through action.
Typically, we cite the misuse and overuse of antibiotics as driving resistance. This can be from not finishing a prescribed treatment of antibiotics for the full course according to your doctor’s instructions. It can also be from the use of antibiotics in farming that we rely on to keep animals healthy and disease free as they’re grown for food.
Further, some diseases are now requiring a multi-drug regimen to try and combat them. We see this in our work with tuberculosis. Taking the right antibiotics at the right time can be particularly challenging, Erin, so we work together on TB and I know this is a topic that we’re both passionate about.
Erin Merritt
Understanding the difficulty in maintaining the necessary antibiotics regimen, especially a multi-drug regimen like with TB, as you mentioned, what are the risks associated with not completing it?
Ryan Howard
The issue with not fully finishing an antibiotic regimen is that the antibiotics aren’t able to kill off all of the bacteria as intended. This leaves behind surviving bacteria that now have encountered evolutionary pressure that is half a treatment of antibiotics that have killed off their weaker neighbors.
From this, these stronger bacteria are able to persist and continue growing inside the patient. Eventually they become strong enough to cause symptoms again, and because they’ve already encountered the antibiotics previously, the exact same prescription won’t necessarily have the same effect.
And it’s possible that you’ve created genetic pressure that can potentially lead to a resistant strain.
Erin Merritt
And what specifically is the genetic basis of AMR?
Ryan Howard
AMR can arise through slight mutations in bacterial genes that code for proteins that the antibiotics target for inhibiting bacterial growth. These mutations are typically a result of random replication error that turns out to be beneficial for the bacterium. In another way, bacteria sometimes transfer resistance genes between one another on plasmids.
Erin Merritt
Ryan’s work with TB serves as a case study for future AMR and how to beat it. But that work is also accompanied by warning signs for the future of antibiotic use.
Ryan Howard
TB provides an interesting case study for AMR. Originally, TB was treatable with just one or sometimes two antibiotics in the mid 20th century. However, as we started using these antibiotics and perhaps also as a function of the incidence of TB globally, we started to see resistance to these antibiotics pretty quickly.
Erin Merritt
But how does AMR impact global efforts to end TB?
Ryan Howard
As the years have gone on, it’s become a cat and mouse game with some of these strains of TB. Today, there are roughly 15 different potential antibiotics that can be used in a TB treatment regimen. And the most common regimens use a four drug combination.
Erin Merritt
And what is the benefit and why use multiple antibiotics in a treatment regimen?
Ryan Howard
Well, by including multiple antibiotics in TB treatment, doctors can reduce the overall treatment time, increase effectiveness, and reduce the chance of relapse.
For instance, in multi-drug resistant TB, a treatment using Bedaquiline, Pretomanid, Linezolid and Moxifloxacin has been shown to be effective while also reducing treatment down to six months compared to the previous treatments, which would last up to 20 months and included other antibiotics which have much more severe side effects.
With respect to AMR, using four drugs really helps make sure that you’re eradicating all the bacteria causing disease.
Erin Merritt
So with so many different antibiotics and different possible resistances and treatments, how do clinicians decide what to give a patient?
Ryan Howard
Yeah, this is really where our work comes in. Clinicians rely on diagnostic tests to assess the antibiotic susceptibility of a patient’s disease, in this case pulmonary TB, to get information on what antibiotics to prescribe to treat that patient’s individual case.
We work on this in two main ways. In the first way, we do 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.
Erin Merritt
That’s pretty amazing that you can go from sample to disease detection and AMR determination that quickly.
Ryan Howard
Yeah, but it’s also really important to get it right if you’re relying on these rapid diagnostics. For instance, we’re seeing an outbreak on the other side of the world where due to selective pressures from the ubiquity of a certain rapid test, TB has evolved resistance outside what the test can detect and is now spreading widely throughout a subpopulation.
I think in this particular case, there needs to be an updated test or an accessory test deployed to detect this particular strain.
Erin Merritt
So if the rapid test can’t identify the resistance, how would you find out what to change to make sure you can identify it?
Ryan Howard
So that brings me to the second way in which we work on this problem, which is by doing full genetic sequencing of TB isolates and 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 kind of a “know your enemy” type thing.
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 to make rapid diagnostics more accurate.
So in this case, we could sequence that strain that’s 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.
All of the sequencing of mutant strains is being compiled by researchers globally 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.
Erin Merritt
So what does the future hold and is there any reason for hope?
Ryan Howard
Well, I think it’s safe to assume that things are probably going to get a little worse before they get better with AMR, but I’m an optimistic person and I know that we can figure this out.
I think making people aware of the problem and educating the public on the importance of finishing their antibiotic prescriptions and maybe not using antibacterial hand soap when they don’t need it are steps in the right direction.
However, ultimately, we’re going to need larger changes, including new and better antibiotics, as well as systems to limit their immediate use in our healthcare system.
Longer term, things like new vaccines to current AMR pathogens and changes in how we use antibiotics in agriculture will go a long ways towards making sure that we have these vital antibiotics when we really need ’em.
