Dr. Scot Dowd, PathoGenius

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    Harrison
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      Next in our series of completed interviews is a video distillation from our meeting with Dr. Scot Dowd. Our interview illuminated some of their “game changing” diagnostics in the areas of chronic bacterial infections and “biofilms.”

      See the interview here, an excerpt is below.
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      PathoGenius, Lubbock, Texas
      Interview with Scot Dowd, PhD

      RL: So what is the “specific problem” that you are working on currently?

      SD: We are at the cusp of what we set out to do: find out what was creating the recalcitrant chronic wounds. What we found is that it’s a very definitive universal boundary to this healing process and that being the biofilm, the bacteria, the fungi, the yeast, that are in these things. So our first goal there was to identify what’s there. What’s there and how much. And then ultimately how can we apply both the biofilm based wound care, develop new diagnostics to tell us what’s there, and then identify therapies that would combat what we are finding in those wounds.

      And again, long story short there, the biofilm-based wound care principles worked very nicely and by themselves improved the healing trajectory of chronic wounds. Then when we applied diagnostics and were able to actually see and know what the bacteria, what the fungi area in each individual wound, then we can target say systemic therapies and specific therapies toward that. And then cut to where we are now, we have targeted therapies that are patient specific and so we identify what’s in the wound, what ratio the bacteria, the fungi are in, and then we can have a targeted therapy for that. So we’ve gone from, and these are very good numbers actually, a wound that would have otherwise taken 166 days to progress toward healing we can now get healed in about 46 days. That’s a dramatic improvement and that just goes to show what biofilm-based wound care accurate diagnoses of a biofilm infection and patient specific targeted therapies can do. That’s tremendous..would you rather have a chronic wound for 166 days or would you like to get rid of it in 46 days?

      RL: What can you tell us about pathogens that are infecting patients? Is there any commonality among them?

      SD: Certainly there are what we would consider major pathogens that occur, and let’s take chronic wounds as an example. What we find there is that there’s your Staph aureus’, your Pseudomonas aeruginosas, there’s your major pathogens. Is there a commonality among chronic wounds…

      Well the opposite is just the case; every chronic wound we looked at has a different profile, a different set of pathogens, different organisms that group together in these chronic wounds, and we’ve kind of simplified that. Because it’s a huge diversity. And we’ve put it into what’s called a functional equivalent pathogroup. So what we are considering there and building the cases for these things is that groups of pathogens can get together and as a consortium, as a synergistic group they can create a pathogen, pathogen-like system with the host. And so, you might have four or five different bacteria, one of which is a common pathogen. The others which are anaerobes and other groups that can all combine together and they all occur together in this chronic wound and that chronic wound is just as chronic as another one which has a completely different group.

      So, ultimately what you are getting is different types of organisms grouping together and their genetic content contributes or equals to a functional pathogen. And that’s kind of the very nebulous futuristic approach we are taking is that you can’t just look for the one thing in many types of chronic infections because they are multiple organisms. . So, you really have to take the whole into account and you can’t discard one member of the group because a textbook somewhere has defined it as a commensal organism. Well, most of the pathogens that we know of were at one time considered commensal. And then they were considered, considered opportunistic pathogens and they slowly became known as pathogens, primary pathogens. And there are many examples of this. And so as an example and probably answering one of the future questions, we are coming to find that Corynebacterium, which is often considered a, what, traditional diagnosis may consider a contaminant or a commensal flora, we are finding that these are very predominant in chronic wound infections. The biofilm infections of chronic wounds. And if we can knock down the Corynebacterium the wound gets better…

      RL: While we are on the structural aspects of biofilms, can you talk a little bit about how genes can be conferred regarding antibiotic resistance within the biofilm. What is actually happening inside a biofilm community?

      SD: Any time two bacteria come into proximity that have a compatible genetic makeup, there is the potential for genetic exchange, be it through phage or through conjugation or through the basically the uptake of environmental DNA fragments. Bacteria in general have a very plastic genome. They, for want of a better word, they evolve very rapidly; if you have a plasmid and it has an antibiotic resistance gene and that bacteria that has that plasmid comes into close contact proximity to another organism which has a genetic makeup compatible with that plasmid, that plasmid can be transferred and that secondary organism can then propagate with that plasmid and thereby benefit from the resistant genes which were contained within that plasmid.

      So that’s a very simplistic type of description of how this can occur. So you are talking proximity and genetic compatibility and ergo in a biofilm you might improve that proximity. But I don’t think, and this is speculation and just opinion, I don’t think a biofilm itself is going to foster or increase the transfer of genetic information between organisms, anymore than growing it in a broth in the laboratory would allow that to happen.

      RL: Can you comment on any of the statistics we talked about earlier? It’s really hard to get facts and figures on the number of people affected by chronic biofilm infections. For example, HAI’s, there is over 100,000 people that die each year. Well over 500,000 almost 600,000 that get infections themselves that become chronic and probably close to 1 million that suffer from some kind of bacteremia. So, any comments on this 17 million number across 10 different specialties or 17 million people that have been infected by chronic infections?

      SD: 17 million is a conservative estimate based upon what we could find in the literature. And that’s kind of a number that’s now tossed around quite a bit. If you think in terms of what infection is and what bacteria do, essentially a bacteria wants to attach to a surface. It, in clinical training we are given this vision of bacteria as these very, they are basically swimmers. And they swim around in this liquid pool and they are happy and that’s the only form they come into. But, by nature, bacteria want to attach to a surface. And indeed, in the body, apart from the blood, apart from actively flowing channels of fluid, the bacteria, when they cause an infection are, by nature going to attach.

      And this could be as simple as attaching to the surface of the intestine. And so bacteria by nature are going to attach and bacteria by nature are going to secrete extra-polymeric substances that allow them to better attach. And therefore, you have two things, bacteria want to attach, bacteria want to secrete substances to help them stay attached.

      So I think the, the statistics around how many infections are caused by biofilm bacteria, I think it’s a very conservative estimate. I think most infections have a biofilm component in one shape form or another. That’s of course speculation. It’s me being a biofilm scientist and wanting this obviously, but not wanting it for the patient but certainly wanting to apply it to every system. Certainly there are planktonic infections and bacteremia. But if you think in terms of what an infection is, what it’s causing, then we are typically dealing with attached bacterium, attached microorganisms and, by nature, bacteria fungi are going to want to become biofilm phenotype. And certainly when we apply therapies, say sub-therapeutic dose of antibiotics hits a bacteria, it’s going to force it more into that biofilm phenotype. of how many infections are caused by a biofilm related phenotype organism. That’s very speculative.

      RL: We’ve been talking a lot about bacterial microbes but certainly viruses, fungi and all these other microbes work together or are found in biofilms. For example, there was one study that showed how Candida significantly increased the antibiotic resistance of a biofilm. So can you talk a little bit about all of these other little friends that sort of cooperate together within the biofilm community?

      SD: So again, taking it back to chronic wounds which has for the past two years has been our primary and indeed only focus. What we have found and we screened maybe a thousand different wounds I think the number was 915 different chronic wounds, and 23% of those had a very significant yeast component. And so that fungi are important components of the polymicrobial makeup of biofilm infections and indeed in wounds. 23% of the 915 we looked at had a fungal component. And this is 25% of the total microbial composition and above.

      Many of these chronic wounds had 95% yeast versus bacteria. So, we can’t really assume that bacteria are causing chronic wound recalcitrance. We have to take into account that fungi can be a major component of those. And essentially what we have found is that if you ignore the fungi before the diagnostics came online and were validated for fungi, those wounds which were not responding to therapy, many of those (and it’s a higher percentage) had a fungal component. But then when we were able to identify that fungi were associated with those infections, those wounds get better. And so ergo we target the fungi; that wound starts getting better immediately. So fungi are a major component of the recalcitrance of these chronic wounds.

      RL: We haven’t really talked about virulence. Again, focusing on the uninitiated, I include myself in this group, can you talk a little bit about virulence and how that plays into your diagnostic and treatment processes?

      SD: Virulence is a very subjective word and many times we want to correlate virulence with a specific gene. And so you have toxin genes which ergo cause a cell death. And so this toxin gene creates this effect. Ultimately what we are talking about when we are talking virulence is, and take it back to chronic wounds again, is it virulence that a group of organisms gathers together their genetic content, which may not have a notable virulence factor associated with it, creates chronicity in this wound. Basically develops a relationship with the host such that the host cannot heal itself. So we have a group of organisms with a genetic makeup which creates chronicity. Does that equate with virulence?

      And that’s, that’s kind of where I struggle with the concept of what virulence is and is not. And so certainly we have microorganisms that have notable virulence factors. Bacillus anthracis. And so we know if it has the X plasmids Bacillus anthracis is highly pathogenic. Without those plasmids it’s not as pathogenic. And so we know that there are virulence genes that influence the progression of disease. But what we don’t have a full grasp on, what I think miss…what I think is missing from our understanding is how organisms can gather together and synergistically (although they may not have a traditional highly publicized virulence factor) they can have the same impact on the chronicity of the infection that a single pathogen that has several virulence factors, publicized virulence factors can have. And so that’s where the concept of functional equivalent pathogroups comes in…

      RL: So, let me get this straight — your new diagnostic approach technology can detect and characterize up to 90% of all microbes?

      SD: Bacteria and fungi.
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