A novel porin regulates polysaccharide capsule formation, a key virulence factor in the top priority human pathogen Acinetobacter baumannii

Acinetobacter baumannii is a multidrug-resistant WHO top-priority pathogen, urgently requiring
novel therapeutics. One major challenge in combatting A. baumannii is its phenomenal
heterogeneity, limiting the development of therapeutic approaches. The presence of a protective
capsule, a key factor mediating both resistance and virulence, is broadly conserved. However,
despite its vital role in pathogenesis, capsule regulatory mechanisms remain largely elusive. To
address this knowledge gap, my host laboratory conducted a density-based screening, which
identified an uncharacterized porin-like protein, as a novel capsule regulator. In my project, I will
conduct an in-depth functional and mechanistic characterization of this new protein. I will test
alterations in capsule formation, drug resistance and virulence through biofilm formation assays,
phagocytosis and serum-killing susceptibility assays, and in vivo virulence studies. To elucidate the
protein function(s) as a novel capsule regulatory porin, I will combine cutting-edge structural biology
analysis with protein-polysaccharides interaction studies, proteomics, and metabolomics. My project
will provide critical insights into the capsule formation mechanism and related bacterial virulence,
thereby offering novel therapeutic targets for future interventions