About
Assistant Professor
Department of Medicine
Lundquist/Harbor-UCLA
Mentors:
Michael Yeaman, PhD, Lundquist Institute – UCLA
Yan Xiong, MD, PhD, Lundquist Institute – UCLA
Liana Chan, PhD, Lundquist Institute – UCLA
Multidisciplinary Expertise:
MRSA pathogenesis, host–pathogen interactions, antimicrobial resistance, bacterial gene regulation, translational infection models
Project Description:
Methicillin-resistant Staphylococcus aureus (MRSA) frequently causes skin and soft tissue infections (SSTIs) that can disseminate to life-threatening bloodstream infections (BSIs). Successful dissemination requires rapid bacterial adaptation to distinct host microenvironments. This project tests the central hypothesis that bicarbonate (HCO₃⁻), abundant in blood but scarce in skin, serves as a physiological signal that reprograms MRSA virulence and antibiotic susceptibility during skin-to-blood transition. Preliminary data demonstrate that HCO₃⁻ represses wall teichoic acid synthesis, downregulates key adhesins, induces the AraC-family regulator sabR, and restores β-lactam susceptibility in select MRSA lineages. Using complementary in vitro, ex vivo, and in vivo approaches, the proposed studies will define how HCO₃⁻ shapes virulence factor expression across tissue contexts, delineate sabR- and cap5P-mediated pathways driving this adaptation, and test their relevance to dissemination and β-lactam efficacy in a murine SSTI model. These studies provide mechanistic insight into host-driven MRSA adaptation and identify translational opportunities to optimize antibiotic therapy.