Microbiology Ph.D. Thesis Defense- Veda Khadka (Lieberman Lab)

Monday April 22, 2024 11:00AM Room E25-119/121

Abstract:

The skin is the body’s largest barrier organ, and as such hosts roughly one million bacteria per square centimeter over its 1.8m2 surface area. As a barrier organ, the skin not only provides a physical layer of defense against these microbes but an immunological one as well. Immune cells present in deeper layers of skin are in constant dialogue with the microbes present on the surface, and these interactions have far-reaching consequences for host health. Here, I interrogate the dynamics of the skin microbiome and consequences of host-microbe interactions when the skin barrier is damaged.

The skin as an external organ is subject to frequent stressors encountered in daily life, and can also be compromised due to genetic factors that weaken the barrier and predispose the host to inflammatory skin diseases. On healthy adults with an intact skin barrier, the skin microbiome is relatively diverse and stable. When the skin barrier is disrupted — either by daily stressors or genetic factors — the composition of the microbiome abruptly shifts to a less diverse state with an abundance of Staphylococci. Staphylococci have been shown to be important modulators of the host immune response and can improve host barrier repair from damage by wounding or parasitic infection during health. Much less is known about immune interactions with skin resident microbes like Staphylococci during barrier damage, however.

In this work, I investigate the skin microbiome dynamics underlying a common inflammatory skin disease, atopic dermatitis (AD). During flares of AD, the pathogen Staphylococcus aureus rises to dominate the skin microbiome, and I show that relative abundance of S. aureus decreases in patients who are treated with a combination of conventional therapies and dilute bleach baths. Next, I use an animal model to interrogate how the host responds to skin resident microbes when the skin barrier is damaged. Although the protective effect of skin resident microbes like S. epidermidis during health have made members of the skin microbiome attractive targets for development into probiotic therapies, I show that common skin microbes ubiquitously delay skin barrier repair.

Together, these works suggest a mechanism by which the skin microbiome can exacerbate disease during barrier damage, such as during AD, and describe the underlying dynamics of the skin microbiome during treatment for AD.