Similarly, the strain 1002 of C. pseudotuberculosis was already tested as a possible live attenuated vaccine against CLA due to its natural low virulent status, and administration of this bacterium to goats did not cause lesions formation [23, 56]. The molecular mechanisms leading to the low virulence of the 1002 strain however remain undetermined so far. We believe that non-secretion of PLD might be one of the main factors

responsible for the lowered virulence of the strain. Importantly, we currently cannot affirm that the 1002 strain does not produce this protein while MRT67307 molecular weight infecting a mammalian host. Besides, this strain still retains the capability of causing localized abscesses and disease in susceptible mice (Pacheco et al., unpublished results). Other proteins believed to be associated with the virulence of C. pseudotuberculosis were also identified exclusively in the exoproteome of the C231 strain, namely FagD and Cp40 (Table 1). The former protein

is a component of an iron uptake system, whose coding sequences are clustered immediately downstream of the pld gene in the C. pseudotuberculosis genome [6]. MM-102 molecular weight The latter protein is a secreted serine protease shown to be protective against CLA when used to vaccinate sheep [57]. Table 1 Formerly and newly identified‡ exported proteins that may be associated with the virulence phenotype of Corynebacterium pseudotuberculosis strains Protein Descriptiona GenBank Accession Identified in the exoproteome of the strainb: Orhologs found in other Corynebacteriac: References     1002 C231 Pathogenic Non-pathogenic   Phospholipase D (PLD) ADL09524.1 No Yes Yes No [54] Iron siderophore binding protein (FagD) ADL09528.1 No Yes Yes Yes [6] Serine proteinase precursor (CP40) ADL11339.1 No Yes No No [57] Putative iron transport system binding (secreted) protein ADL10460.1 No Yes Yes No [12] Glycerophosphoryl diester phosphodiesterase ADL11410.1 No Yes Yes No This work. [72] Putative surface-anchored

membrane protein Epothilone B (EPO906, Patupilone) ADL20074.1 Yes Yes Yes No This work. Putative hydrolase (lysozyme-like) ADL20788.1 Yes Yes Yes No This work. Putative secreted protein ADL21714.1 Yes Yes Yes No This work. Putative sugar-binding secreted protein ADL09872.1 No Yes Yes No This work. ‡ The inclusion criteria followed three main requisites: (i) experimental detection of the proteins in the exoproteomes of the pathogenic C. diphtheriae and C. jeikeium; (ii) non-detection of the proteins in the exoproteomes of the non-pathogenic C. glutamicum and C. efficiens; and (iii) in silico detection of ortholog proteins in pathogenic, but not in non-pathogenic, corynebacteria through search of similarity against public protein repositories. a This protein list is not meant to be all-inclusive.