Episode 48: Staph’s secret superpower and their accomplice Streptococcus
Two new studies from the Society for Investigative Dermatology (SID) conference reveal how staph bacteria use clever strategies to disarm the skin's barrier maintenance function and work with other bacteria to amplify inflammation. Join us for an interview with Dr. Nathan Archer and Dr. Laine Feller from John Hopkins School of Medicine who explain how Staph aureus bacteria uses its superantigen superpower to hinder lipid production ... and more new research from this year's SID meeting. If you like our podcast, please consider supporting it with a tax deductible donation. Read the transcript.
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Korey Capozza: Hi there. I'm Korey Capozza, Executive Director of GPER, and I just returned from the Society for Investigative Dermatology meeting in San Diego. This is the annual meeting for people who study the skin and skin conditions, and there tends to be a lot of research presented on basic science questions about how the skin works.
I was intrigued by several studies that investigate the curious role of Staph bacteria in eczema development and flares. We know that this bacteria tends to overgrow and dominate on the skin of people with [00:01:00] eczema. And it can start to show up even before there's an outward sign of the condition. But there's been a longstanding question about what its role is. For example, is it a bacteria that just prefers the environment seen on eczema affected skin, an environment where there's a weakened barrier and higher pH? Or is the Staph actually causing the damage to the skin in the first place and adding fuel to the fire of the eczema flare? Or both?
One thing we do know is that this bacteria has evolved to be exceptionally clever at using various strategies to manipulate the skin environment to create a favorable niche for itself. A case in point is a study that was presented at the meeting by a team from Johns Hopkins University that looked at how Staph bacteria produces a toxin that stimulates the immune system to overreact. And this group found something new that this toxin Staph super antigen also interferes with the skin's ability to make [00:02:00] lipids. These are fats that are important to strengthening the skin barrier. Here they are being interviewed a few days after the conference by our podcast producer, Lynita Howie.
Lynita: I'm here with Dr. Archer and Dr. Feller who were at the Society for Investigative Dermatology Conference in San Diego last week. I know you caught up with our Executive Director. Korey Capozza at the conference. So first up, can you please introduce yourselves?
Dr. Archer: I'm Dr. Nathan Archer. I'm an Assistant Professor in the Department of Dermatology. We're at Johns Hopkins School of Medicines.
Dr. Feller: And I am Dr. Lane Feller. I am actually a veterinarian and I'm doing my PhD and I'm a graduate student in Dr. Archer's lab.
Lynita: Tell us now a little bit about the study that you presented at the SID conference and what you discovered in that study.
Dr. Archer: The study was to understand how Staph aureus, colonizes the skin. And that's [00:03:00] because Staph aureus is almost universally colonized on the skin of patients with atopic dermatitis. And the abundance of Staph aureus on the skin correlates with disease severity. And so ultimately if we can eliminate Staph aureus colonization on the skin, we can reduce the severity in patients with atopic dermatitis.
And so we were really interested in studying a Staph aureus protein family called superantigens. And it's been previously shown that superantigens correlate with disease severity in atopic dermatitis patients. But we were interested in understanding how it might affect the colonization of Staph aureus on the skin.
Dr. Feller: There's several very famous superantigens. Probably the most famous superantigen is called toxic shock syndrome toxin. Associated with like tampons, but they're actually produced by many different Staph aureus species, and there's a family of about 26 of them.
So it's a pretty large protein family. We were actually looking [00:04:00] initially at toxic shock syndrome toxin and how it affects Staph aureus colonization on the skin.
Dr. Archer: And so what we found in this study is that super antigens were affecting this gland in the tissue called sebaceous glands. And we know that sebaceous glands are important for producing lipids on the skin. And these lipids are important for keeping the skin hydrated as well as controlling the bacteria that grow on the skin.
And so we hypothesized that perhaps Staph aureus is trying to reduce the amount of sebaceous glands in the skin and the amount of lipids that they produce to help it colonize and help it overcome these antimicrobial lipids that the, the skin normally produces.
Lynita: Okay, so sebaceous glands are like microscopic pockets, I guess, in our skin. Is that right? And they produce lipids and things that might help control the overgrowth of Staph on the skin. And so in a way, Staph is trying to circumvent that process. [00:05:00]
Dr. Archer: What's really fascinating is children have smaller sebaceous glands than adults. And when Children go through puberty, their sebaceous glands expand. We think this might help to explain why children are so much more susceptible to developing atopic dermatitis than adults, is that they have smaller sebaceous glands that produce less lipids.
And this might make it easier for Staph aureus to colonize the skin in children than adults.
Lynita: What I'm understanding, these sebaceous glands are really one of the weapons that our body has against Staph aureus, but when we're young, they don't have the same fighting capability that they do when we hit teenagers. When people often discover things like pimples when they get a bit overactive, possibly, is that right?
Dr. Archer: Right. Yeah. So this is what we're working on now, is to make that connection, that link, which, don't fully know.
Lynita: What can we do with this information? Can we add some of these lipids that are normally in sebaceous glands?
Dr. Archer: Yeah, that's exactly right. So, you know, we can think about, can we target. [00:06:00] And neutralize superantigens. Can we restore lipids that might not be produced at the right amounts on the skin of children? And can that help to control Staph aureus colonization? Yeah, I think you absolutely nailed it on that.
And so what I think what's even more interesting is that Staph aureus colonization doesn't only affect atopic dermatitis patients, it also affects other skin disorders. Such as cutaneous T-cell lymphoma, bolus pemphigoid. What am I missing… psoriasis. Yeah. And maybe even psoriasis as well.
So, hopefully what we find in these studies in atopic dermatitis can be more broadly applied to other skin disorders as well, that involve Staph aureus colonization.
Lynita: Fantastic. How does this add to our existing knowledge, do you think? Is this new that the superantigen in trying to fight the effect of lipids in the sebaceous glands.
Dr. Feller: Yeah, it's actually something we're very excited about because there hasn't really been a lot examined with how superantigens actually are involved in atopic [00:07:00] dermatitis pathogenesis, but even more so, like we do not really understand how Staph colonizes the skin.
So understanding those initial mechanisms for how it's able to initiate that colonization is really important. And it was interesting 'cause we realized that, patients with atopic dermatitis can have abnormal lipid composition on their skin and have this abnormal sebum secretion. But there really has not been a lot into why that is, or how that makes disease worse. So we really think this could be a really exciting new area to explain that.
Lynita: That's really cool. And then… Maybe we can treat by replacing these lipids.
Dr. Feller: Exactly something that's already in the skin that might just be depleted.
Lynita: So what can we, as parents do with this information?
Dr. Archer: Is a great question that I don't have an answer for right off the bat. But maybe just be mindful that there are gonna hopefully be new therapies down the road that we can help with.
Dr. Feller: We're still in the early stages of this [00:08:00] project, but I do think it's exciting that there is still a lot of continued research into this area, so I think for patients there are new therapeutics that are in the process of being developed, so there's a lot of hope on the horizon I thin.
Lynita: Oh, great. Hope, hope is good… Leading really onto the next question is what's the future for your research?
Dr. Archer: As Laine mentioned earlier, Staph aureus isn't the only bacteria that produces these superantigens. So we're really interested in exploring what other pathogens are producing super antigens, number one. And number two, the ones we do know that produce superantigens are generally all skin pathogens. So is this just a very broad common mechanism for pathogens to overcome our skin barrier and colonize the skin and then lead to skin disease?
Dr. Feller: I think also we're hoping to understand how they're affecting sebaceous gland maturation, we can maybe specifically therapeutically target that. And so I think those are all of our hopes going forward.
Dr. Archer: Yeah. And as well as like get sebaceous glands to produce more of these [00:09:00] antimicrobial lipids. And so can we get maybe better fine control of these sebaceous glands that we don't know as much about as we do of other structures in the skin.
Lynita: Sure, my brain's racing with all your research. I normally, when I interview people, I have read their papers, but because you presented at a conference, I really was coming into this quite blind and not knowing what we were gonna talk about. But it's really got me thinking, you know, that not everybody has Staph aureus on their skin, and not everybody that has Staph aureus on their skin has eczema. So why is it that some people have Staph but not eczema and other people don't have it and do have eczema? But maybe the sebaceous glands and their ability to produce lipids to counteract the superantigen… Dunno, maybe there is a role in there that we haven't really got a handle on yet, that your work might reveal what's going on.
Dr. Feller: We do know that, you know, Staph in and of itself is extremely heterogeneous and the variance factors it's able to make. So not all [00:10:00] Staph make superantigens. Some make different combinations. So that is one potential variable. But then also, you know, the proteases they make, the other kind of toxins that they produce and how they affect the skin, all of that definitely probably ties into why some people develop eczema and some people not. And honestly, we really don't understand. Some people are colonized asymptomatically by Staph aureus, and we don't really know when it becomes pathogenic. And those are a lot of things that are being researched in the field, and hopefully we'll get a better handle on.
Dr. Archer: Yeah, atopic dermatitis, you know, is itself a heterogeneous disease. You know, some patients have genetic mutations in their skin barrier, right? That might make them more susceptible or not. And there's a lot of, you know, complex interactions happening between the environment, the skin, the bacteria that all, I believe, come together to lead to inflammation or not.
Lynita: So, what I'm hearing is we are working with a, a heterogene..that word. We are working with a very [00:11:00] diverse disease.
Dr. Archer: Yeah. yes. yes.
Lynita: and we're working with a pathogen, Staph, that is also quite diverse. So there might be subtypes that are more pathogenic than others. It makes your job pretty challenging actually.
Dr. Archer: Yeah, but we love it. We enjoy it. Yeah. And knowing that, you know, we can hopefully, you know, help patients someday, I think is, is a great motivating factor as well.
Lynita: Well, we appreciate the work you're doing. One thing for sure, you've put your research on our radar, so we'll be following what you come up with and hoping that it leads to easing the suffering of our kids. Thank you so much for the work you do and for your time today talking to us.
Dr. Archer: Great, and thank you for having us.
Dr. Feller: Yeah, it was so nice talking to you.
Korey Capozza: A second study that was presented at the meeting from Dr. Richard Gallo's lab at the University of California, San Diego investigated a different strategy that Staph bacteria used to manipulate the skin immune response. The team led by Teruaki Nakatsuji found that there is [00:12:00] an increase in a second kind of bacteria, Streptococcus or Strep species on the skin of children with eczema. The investigators wondered why these two bacteria seem to coexist together in greater abundance in an eczema skin environment.
Using different models, including a mouse mode, they found that when the Staph aureus bacteria was combined with a common Strep bacteria found on children's skin, the inflammatory effects were greatly amplified, suggesting that these two bacteria work as a kind of dynamic duo to cause greater damage to the skin barrier.
These two studies start to show the surprising ways that Staph bacteria has evolved to be a particularly troublesome pathogen for children with eczema. An ongoing research is looking at new strategies for controlling the bacteria, including new types of creams that may restore the balance in the delicate skin microbiome.
We're looking forward to learning more about [00:13:00] this topic, which we'll share on our podcast, and I'm looking forward to sharing more interesting breakthroughs with you from the upcoming allergy research meeting in Glasgow, Scotland in June. Thanks for joining us.
