Bacter to the Future

Wee Beasties

Time to talk about the most widespread infection in the world, Helicobacter pylori. Following the accidental abandonment of incubated plates, H. Pylori colonies were discovered, launching a larger investigation into the microbiology of the human stomach. More research is needed on this disease-causing gram-negative bacterium, but our hosts provide the basics of its characteristics, transmission routes, and prevention in this episode.

More about Helicobacter pylori:

• Persistence strategies of the bacterial pathogen Helicobacter pylori
• Gastroenteritis and Transmission of Helicobacter pylori Infection in Households
• Nobel prize is awarded to doctors who discovered H pylori
• Pathogen Safety Data Sheets
• Trends in Hospitalizations for Peptic Ulcer Disease
• H pylori finds its home

Stay tuned for more episodes, posting on the first Thursday of each month. Subscribe to our show wherever you get your podcasts and find more info at weebeastiespodcast.com  

The Wee Beasties podcast is a production of Nephros, Inc., a company committed to improving the human relationship with water through leading, accessible technology.

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SHOW TRANSCRIPT:

Christian: I am back with Dr. Kimothy Smith. Kimothy, welcome back!

Kimothy: Thanks, Christian.

Christian: All right…how are we doing today Kimothy? How’s life?

Kimothy: I’m feeling a lot of stress, and I’ve got a pain in my stomach. I think I’m getting an ulcer.

Christian: Today’s the right day to have this conversation, I think. We’re talking about pathogens on this podcast, so I hear?

Kimothy: Cool! Let’s go.

Christian: I was watching that documentary, Human Nature, last night. Have you seen it yet? It’s about genomics, personalized medicine using CRISPR cas9 and the scope of genetic and molecular engineering to cure disease, but also do wild projects like bringing back a wooly mammoth. Cool stuff. Worth a watch if you have some time.

Kimothy: I’ll check it out, but I tend to be a bit old school. And, I don’t mean to go too deep on the old school stuff here, but, have you seen Jurassic Park? Do you really want to bring back a wooly mammoth?

Christian: What is that line from Jeff Golblum in Jurassic Park? “Your scientists were so preoccupied with whether or not they could, they didn’t stop to think if they should?”

Kimothy: Yeah, definitely.

Christian: Well, what’s our next waterborne pathogen?

Kimothy: Apropos to my ulcer generation, it is Helicobacter pylori.

Christian: H. pylori, I’m not super familiar with this one, but if memory serves this is spiral-shaped bacteria that makes a home in your stomach and can cause ulcers and even stomach cancer in some cases, right?

Kimothy: Yeah, you’re on the right track, Christian. According to a 2013 report1 in Nature, H. pylori is the most widespread infection in the world, infecting at least half of the global population. The World Health Organization (WHO) recognized H. pylori as a group 1 carcinogen in 1994, but the backstory on this little bug isn’t that straight forward. H. pylori was discovered more recently, in comparison to the other microorganisms we’ve discussed – it was discovered in 1983 – and, interestingly enough, it was first found as a colony in the human stomach in a really unexpected stroke of luck after two doctors were trying to demonstrate a connection between the severity of gastric distress experienced by their patients and the number of bacteria present. In part, this discovery prompted scientists to begin a larger investigation into the microbiology of the human stomach using 16S rRNA analysis – and now we know that the stomach and the rest of the human gut has an extraordinarily diverse microbiome of bacteria which is critical to our immune response and other autonomic faculties. And I must tell you, Christian, as a side note, I’ve heard an urban legend that your microbiome can determine if you have a sweet tooth or not. Have you heard that?

Christian: I have not, but I’ve got a horrible sweet tooth. I’m always wanting sweets. So, I’m sort of wondering if we should run a 16S rRNA analysis of my gut biopsy.

Kimothy: Keep your microbiome to yourself, please.

Christian: Yeah, so this was part of what catalyzed the gut microbiome frenzy in the 90’s. But wait, what was the stroke of luck? And, if good bacteria is so critical to our gut and immune response how is H. pylori, a pathogenic bacterium, able to stay alive in there?

Kimothy: Yeah, Christian, I’m glad you asked. So, the stroke of luck was in the successful culture. The two Australian doctors credited with the discovery just mistakenly left a plate in the incubator a lot longer than they had intended, and they just happen to get H. pylori colonies on it. Those that have worked with H. pylori before will know just how persnickety the bacteria is – it is exceedingly difficult to grow outside of its habitat.

Christian: And why is that?

Kimothy: Well, let me get into the weeds a bit here. So, like many of the other pathogens we’ve discussed, H. pylori is a gram-negative bacterium, which means it has that extra LPS (lipopolysaccharide) barrier on its outer membrane. So, for starters, its more protected simply by its composition as a gram-negative bacterium. However, H. pylori has a really cool mechanism that allows it to transform its shape when it’s under stress – examples of stress may include a change in pH or salinity, or an increase in the gases present – like nitrogen, carbon dioxide, and oxygen.

Christian: Uh huh…so what does it change its shape to?

Kimothy: Well, as I was saying a moment ago, H. pylori is hard to grow on a plate outside its ideal habitat. It turns out that even in its ideal habitat, the stomach, the bacterium only thrives in these really specific conditions of pH and gas and any deviation from those conditions will cause the cells to become dormant and actually change shape. So check this out: H. pylori is spiral or helix-shaped (that’s where the name comes from, Helico-bacter) and form follows function here, so it needs to burrow into the epithelium in the stomach lining in order to survive, so it uses its spiral shape and several flagella to literally corkscrew itself into our stomach to take residence. But, if the cell becomes stressed because a change in any of those conditions – pH, salt, gas, or temperature – it will slow down its metabolic machinery and change from its spiral shape and into a coccoid form. It’s still unclear if this transformation under stress is a selected adaptation or something else. Several studies point to H. pylori’s transformation as an evolutionary adaptation to cope with stress and others show no relationship. There need to be more experiments to tease this out, but it is clear that a VBNC state is common with H. pylori, which again makes this a very, very difficult organism to culture from biopsies.

Christian: OK, we did get pretty deep there, let me just recap real quick: H. pylori is a gram-negative pathogen that is spiral (helix-shaped) with several flagella, which make it very motile; it is really selective about its environment (which is the stomach) and it doesn’t grow well at all outside of that environment, in fact it usually enters a VBNC state if it becomes stressed in any way and when it’s stress it changes shape into a coccoid form – this is a smaller spherical shape, right? I think the etymology of coccoid is actual berry in Greek, right? So, it transforms from a rod-spiral to a berry-shape? Lastly, and most importantly H. pylori results in the host ultimately getting stomach ulcers and even cancer, right? OK, but we’ve been talking a lot about this pathogen living in stomachs, H. pylori is also in bulk water, though.

Kimothy: Yes, so the route of infection for H. pylori is still a bit mysterious and not always well-characterized to researchers. Contaminated water sources are certainly a means of infection, but so is fecal-oral and mucous-oral routes. This can result from living in close quarters with a large community and just not have access to proper disinfectants on touchable surfaces. Once one person in a close-quarters household acquires H. pylori the R0 in that sample size will increase over time according to a Stanford Medical School manuscript in 2006. R0 is just a term we use to describe the rate of infection to other individuals.

Christian: So the good news, if there is good news, is that educating people on transmission routes and increasing access to disinfectants can likely really disrupt or lower the R0.

Kimothy: That’s right, Christian. I’d like to come back to bulk water and liquid biopsies though if I may for a moment. Because H. pylori is so challenging to culture one of the best and most reliable ways to detect and study H. pylori is by using molecular diagnostic tools such as NGS using 16S rRNA and qPCR. We’ve talked about pathogens that cause pneumonia and acute respiratory infections, we’ve talked about pathogens that infect the blood, and now we have a pathogen that infects your gut with little to no indication of infection in most patients. And although worldwide infection rates are going down, largely because of what you mentioned – access to clean water and surface disinfectants, the best way we can track and surveil this bug is by using these new diagnostic tools. Culturing for this bug is just too time consuming, unreliable, and not specific enough. It’s analog in a digital world.

Christian: All right, well H. pylori…the peptic ulcer disease-causing gram-negative bacterium. One more thing before we go – I know you’re not a medical doctor, but how is H. pylori usually treated? Just a super dose of antibiotics?

Kimothy: Yeah, bacterium is very susceptible to antibiotic regimens, so it can usually be eradicated with a high-powered antibiotic.

Christian: Well, cool deal. We’ll put some links in the show notes to some of these manuscripts we’ve mentioned in case you’re interested. Kimothy, as always, thanks so much for the chat today.

Kimothy: You bet, Christian.