Cryptic species of Paracoccidioides brasiliensis: impact on paracoccidioidomycosis immunodiagnosis

Abstract

We aimed to evaluate whether the occurrence of cryptic species of Paracoccidioides brasiliensis, S1, PS2, PS3 and Paracoccidioides lutzii, has implications in the immunodiagnosis of paracoccidioidomycosis (PCM). Small quantities of the antigen gp43 were found in culture filtrates of P. lutzii strains and this molecule appeared to be more variable within P. lutzii because the synonymous-nonsynonymous mutation rate was lower, indicating an evolutionary process different from that of the remaining genotypes. The production of gp43 also varied between isolates belonging to the same species, indicating that speciation events are important, but not sufficient to fully explain the diversity in the production of this antigen. The culture filtrate antigen AgEpm83, which was obtained from a PS3 isolate, showed large quantities of gp43 and reactivity by immunodiffusion assays, similar to the standard antigen (AgB-339) from an S1 isolate. Furthermore, AgEpm83 was capable of serologically differentiating five serum samples from patients from the Botucatu and Jundiaí regions. These patients had confirmed PCM but, were non-reactive to the standard antigen, thus demonstrating an alternative for serological diagnosis in regions in which S1 and PS2 occur. We also emphasise that it is not advisable to use a single antigen preparation to diagnose PCM, a disease that is caused by highly diverse pathogens.

Serological Diagnosis of Paracoccidioidomycosis: High Rate of Inter-laboratorial Variability among Medical Mycology Reference Centers

“…This is a new species in the Paracoccidioides genera recently described that is endemic in some areas of South America where the patients' sera were reported to not recognize the P. brasiliensis' antigens in conventional serological tests [27]–[29]. This issue could not be addressed here since the 6 reference centers participating in the study were located in P. brasiliensis endemic areas and provided sera only with positive serological results.…”

Paracoccidioidomycosis: level of pulmonary sequelae in high resolution computed tomography images from patients of two endemic regions of Brazil

“…Teixeira et al found morphologic variations between conidia of complex P. brasiliensis and P. lutzii (27). Studies evaluating double immunodiffusion (DID) test with sera from patients infected by different cryptic species complex P. brasiliensis and P. lutzii revealed wide variation in reactivity, suggesting significant differences among these fungi (12,28,29). In 2016, Siqueira et al found distinct patterns of host-parasite interaction and pathology caused by P. brasiliensis and P. lutzii (10).…”

“…PCM can be caused by fungi of the Paracoccidioides genus, comprising P. brasiliensis complex, consisting of four cryptic species (S1, PS2, PS3 and PS4) (2,3,12) and P. lutzii. (initially Pb01, a new clade) (3,6).…”

“…Many studies have explored the evolutionary mechanisms that were responsible for the current geographic distribution of phylogenetic species (S1, PS2, PS3, PS4, and P. lutzii) (2). However, these cryptic species still require further studies to correlate their ecoepidemiology, diagnosis, clinical manifestation and response to antifungal treatments (12).…”

ParacoccidioidesSpp.: Virulence Factors and Immune-Evasion Strategies

“…Indeed, infections reported in endemic areas of P. lutzii frequently present lymphatic-abdominal clinic manifestation, which are not reported in areas endemic for the P. brasiliensis species complex [10]. Also, sera recovered from patients infected with P. lutzii are not recognized by P. brasiliensis antigens and conversely [8, 11–13].…”