Secreted and cell surface proteome analysis of pathogenic Corynebacterium diphtheriae reveals proteins relevant to virulence

Abstract

AbstractCorynebacterium diphtheriae is responsible for the severe upper respiratory tract disease, diphtheria, which can be fatal in healthy individuals without proper treatment. Its interaction with the infected host is crucial to its virulence, secreting diphtheria toxin and a variety of machinery to acquire nutrients for further import into the cell. Additionally, it shares a conserved iron import mechanism with related pathogenic actinobacteria such as Mycobacterium tuberculosis, and contains sortase-mediated anchored cell wall proteins similar to other gram-positive bacteria. Information obtained from secreted and cell-surface proteomes are relevant for the study of diphtheria and related bacterial infections. Mass spectrometry-based proteomics measurements on samples of pathogenic Corynebacterium diphtheriae culture supernatant and cell-surface digested proteins identified greater than 3 times more proteins than a previous similar study. The diphtheria toxin was identified, as well as pathologically relevant proteins involved in iron-uptake and cell adhesion. For instance, 17 proteins predicted to be on the iron-regulated DtxR promoter were identified in cells grown under different iron concentrations, opening the door to performing comparative quantitative proteomics studies on samples where iron sources are modulated. Results of this study serve as a repository for future studies on pathogenic C. diphtheriae uptake.