In past years, various examples have showcased the added value of addressing proteoforms in the field of infectious disease. For instance, for <i>N. meningitidis</i>, which is the etiologic agent of the cerebrospinal meningitis, a specific proteoform of the PilE protein, which plays an important role in bacterial virulence, was found tightly associated with crossing of the epithelial barrier and access to the blood stream. For the same protein, highly glycosylated proteoforms were obtained from patients with evidence of meningitis and linked to immune escape. More recently, O-mycoloylation of membrane proteins (porins) of <i>Corynebacterium glutamicum</i> was found to be a bone fide signal to direct the modified protein to bind to mycomembrane. In clinical microbiology, proteoforms can also be used to differentiate bacterial strains that cannot be discriminated with MALDI-TOF MS, the technique used in routine in many hospital settings for the rapid identification of bacterial pathogens. This talk will review a few of these examples and describe the top-down proteomics (TDP) workflows optimized for these applications, as well as new software tools developed to ease the analysis of TDP data. Perspectives will be discussed.

Expanding the role of proteoforms in the field of infectious diseases

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