The skin microbiome and fungal infections of indigenous Malaysians

Abstract The Orang Asli are indigenous people of Peninsular Malaysia, still leading semi-nomadic lifestyles, with a high prevalence of the skin disease tinea imbricata which is caused by Trichophyton concentricum fungal infections. The relationship between skin fungal infections and the skin microbiome is poorly understood, particularly in these indigenous populations that represent underserved communities. Investigating this relationship in the Orang Asli has the potential to uncover novel interactions between hosts and microbes, elucidate infection mechanisms, and identify therapeutic interventions, as well as contribute towards global databases of the skin microbiome. Understanding this unique fungal pathogen and the disease that it causes may reveal novel host-fungal interactions that have broader implications to our understanding of skin epithelial cell biology, fungal immune responses, and fungal metabolic pathways that affect their host. Our preliminary epidemiologic study on 361 Orang Asli participants characterized the village-specific prevalence of tinea imbricata and enabled the collection of skin samples for Trichophyton culturing and microbiome analyses. Our preliminary metagenomic sequencing data on the skin microbiome demonstrated the presence of known commensal bacteria, such as Staphylococcus, Cutibacterium, and Corynebacterium, providing confidence in our workflow. Additionally, more than half of the microbial taxa in the Orang Asli samples are uncharacterized, indicating the probable elucidation of novel microbes capable of colonizing human skin. Therefore, we aim to conduct (in Aim 1) a larger-scale study to determine the epidemiology of tinea imbricata in a study encompassing multiple villages of the Orang Asli community with diverse lifestyles and infrastructure. We hypothesize that T. concentricum infection is associated with specific skin microbiome features, and that the skin microbiome of the Orang Asli will be highly distinct from analyses conducted in developed urban societies. By utilizing skin microbiome sequencing (in Aim 2) and fungal isolate whole-genome sequencing (WGS) approaches (in Aim 3), we will examine the interactions between the skin microbiome and fungal infections, as well as to model tinea imbricata disease progression. This study is built upon collaborations between the PI, Dr. Yvonne Lim (Universiti Malaya) with NIH intramural investigators, Dr. P’ng Loke (NIH/NIAID), Dr. Julie Segre (NIH/NHGRI), and Dr. Heidi Kong (NIH/NIAMS), with expertise in the host-microbe interactions, skin microbiome, fungal transmission, and field studies.