Abstract
Leishmania (Viannia) braziliensis is the main etiological agent of cutaneous and mucocutaneous leishmaniasis in Latin America. Non-ulcerated atypical tegumentary leishmaniasis cases caused by L. braziliensis have been reported in several regions of the American continent, including the Xacriabá indigenous reserve in São João das Missões/Minas Gerais, Brazil. Parasites isolated from these atypical clinical lesions are resistant to antimony-based therapeutics. In the present study, proteins displaying differential abundance in two strains of L. braziliensis isolated from patients with atypical lesions compared with four strains isolated from patients with typical lesions were identified using a quantitative proteomics approach based on tandem mass tag labeling (TMT) and mass spectrometry. A total of 532 (P<0.05) differentially abundant proteins were identified (298 upregulated and 234 downregulated) in strains from atypical lesions compared to strains from typical lesions. Prominent positively regulated proteins in atypical strains included those that may confer greater survival inside macrophages, proteins related to antimony resistance, and proteins associated with higher peroxidase activity. Additionally, we identified proteins showing potential as new drug and vaccine targets. Our findings contribute to the characterization of these intriguing L. braziliensis strains and provide a novel perspective on Atypical Cutaneous Leishmaniasis (ACL) cases that have been associated with therapeutic failures.
Highlights
In different parts of the world, authors have referred to Atypical Cutaneous Leishmaniasis (ACL) cases as sporotrichoid, reported in Pakistan, but no Leishmania species was identified (Iftikhar et al, 2003), erysipeloid, reported in Anatolia, Turkey, unidentified species of Leishmania (Karincaoglu et al, 2004), recidiva cutis, caused by L. panamensis (Calvopina et al, 2005) or zosteriform, reported in Iran (Omidian and Mapar, 2006)
The L. braziliensis strains from typical (LbTL) lesions were isolated from patients from Belo Horizonte, MG, Brazil, identified as MHOM/BR/95/RR051 and BH17 and from São João das Missões, MG, Brazil identified as MHOM/BR/08/426 and MHOM/BR/09/346
We performed an isobaric tagging and high-resolution mass spectrometry strategy to compare the proteome of L. braziliensis strains that cause atypical lesions (LbAL, n=2) and L. braziliensis strains that cause typical lesions (LbTL, n=4)
Summary
In different parts of the world, authors have referred to Atypical Cutaneous Leishmaniasis (ACL) cases as sporotrichoid, reported in Pakistan, but no Leishmania species was identified (Iftikhar et al, 2003), erysipeloid, reported in Anatolia, Turkey, unidentified species of Leishmania (Karincaoglu et al, 2004), recidiva cutis, caused by L. panamensis (Calvopina et al, 2005) or zosteriform, reported in Iran (Omidian and Mapar, 2006). Leishmania (Viannia) braziliensis is an important Leishmania species that circulates in several North and South American countries. This species can cause a wide spectrum of clinical manifestations ranging from single and typical lesions with a granular background and raised edges, known as cutaneous leishmaniasis (CL), to the involvement of nasal and oral mucous membranes, known as the cutaneousmucosal or mucosal form (Lainson and Shaw, 1998). Possible causes associated with ACL are host immune status (pregnancy, co-morbidities, immunosuppression (Iftikhar et al, 2003; Omidian and Mapar, 2006), environmental factors, and strain of the parasite (Guimarães et al, 2016). L. braziliensis is characterized by variable infectivity, virulence, and response to antileishmanial therapy (Rego et al, 2018; Patino et al, 2019a); there is no consensus on the factors involved in cases of ACL, these data seem to suggest that parasite factors may be more determinant
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