Polymorphism in the gene coding for the immunodominant antigen gp43 from the pathogenic fungus Paracoccidioides brasiliensis

The gp43 glycoprotein is an immune-dominant antigen in patients with paraco ccidioidomycosis (PCM), It is protective against murine PCM and is a putati ve virulence factor. The gp43 gene of Paracoccidioides brasiliensis B-339 i s located in a 1,329-bp DNA fragment that includes two exons, a 78-bp intro n, and a leader peptide-coding region of 105 bp, Polymorphism in gp43 has b een suggested by the occurrence, in the same isolate or among different fun gal samples, of isoforms with distinct isoelectric points. In the present s tudy we aligned and compared with a consensus sequence the gp43 precursor g enes of 17 P, brasiliensis isolates after sequencing two PCR products from each fungal sample, The genotypic types detected showed 1 to 4 or 14 to 15 informative substitution sites, preferentially localized between 578 and 11 66 bp, Some nucleotide differences within individual isolates (noninformati ve sites) resulted in a second isoelectric point for the deduced protein, T he most polymorphic sequences were also phylogenetically distant from the o thers and encoded basic gp43 isoforms, The three isolates in this group wer e from patients with chronic PCM, and their DNA restriction patterns were d istinct in Southern blots, The nucleotides encoding the inner core of the m urine T-cell-protective epitope of gp43 were conserved, offering hope for t he development of a universal vaccine.