Antigenic diversity of MASP gene family of Trypanosoma cruzi

Leão, Ana Carolina; Viana, Laila Almeida; Araújo, Fernanda Fortes de; Almeida, Rodrigo de Lourdes; Freitas, Leandro Martins de; Coqueiro-dos-Santos, Anderson; Silveira-Lemos, Denise da; Cardoso, Mariana Santos; Reis-Cunha, João Luís; Teixeira-Carvalho, Andréa; Bartholomeu, Daniella Castanheira

doi:10.1016/j.micinf.2022.104982

Cited by 3 publications

(5 citation statements)

References 41 publications

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“…Previously identified MASP epitopes that were antigenic in humans 47 did not show high relative seroprevalence in our study. This is in agreement with current evidence: not all MASP genes are expressed simultaneously 48 ; antibodies against one MASP family member may only detect a few parasites from a population 46 , 49 . All this evidence supports the low seroprevalence observed for most MASPs.…”

Section: Discussionsupporting

confidence: 92%

The Trypanosoma cruzi Antigen and Epitope Atlas: antibody specificities in Chagas disease patients across the Americas

et al. 2023

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During an infection the immune system produces pathogen-specific antibodies. These antibody repertoires become specific to the history of infections and represent a rich source of diagnostic markers. However, the specificities of these antibodies are mostly unknown. Here, using high-density peptide arrays we examined the human antibody repertoires of Chagas disease patients. Chagas disease is a neglected disease caused by Trypanosoma cruzi, a protozoan parasite that evades immune mediated elimination and mounts long-lasting chronic infections. We describe a proteome-wide search for antigens, characterised their linear epitopes, and show their reactivity on 71 individuals from diverse human populations. Using single-residue mutagenesis we revealed the core functional residues for 232 of these epitopes. Finally, we show the diagnostic performance of identified antigens on challenging samples. These datasets enable the study of the Chagas antibody repertoire at an unprecedented depth and granularity, while also providing a rich source of serological biomarkers.

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Section: Discussionsupporting

confidence: 92%

The Trypanosoma cruzi Antigen and Epitope Atlas: antibody specificities in Chagas disease patients across the Americas

et al. 2023

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“…Moreover, in trypomastigotes, the bias of multiple MASP variants toward a particular MASP subgroup was revealed [102]. The plethora of MASP and the second largest gene family in T. cruzi, have been presented [105], suggesting that MASP is involved in mechanisms of host-parasite interactions. Furthermore, it is necessary for the infection process, as shown by analyzing mucin-associated surface protein 49 (MASP49) [106].…”

Section: Mucin-associated Surface Proteins (Masps) Familymentioning

confidence: 99%

Possible Chemotherapeutic Potential of Inhibiting N-Alpha Terminal Acetylation Activities to Combat Trypanosome Infections

Ochaya

2024

Infectious Diseases

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New anti-trypanosome drugs focusing on N-alpha terminal acetylation (Nt-acetylation) interference are necessary scientific inputs because currently, many of the drugs in use are unacceptably toxic; moreover, resistance is emerging. Nt-acetylation transfers an acetyl molecule to the N-alpha terminal of a protein by enzymes called N-alpha terminal acetyltransferases (Nats). Nats are grouped according to their amino acid sequence at the N-terminus where they acetylate. It is conserved in all kingdoms of life, and in humans, approximately 80% of proteins are thought to be Nt-acetylated. NatA-NatF and NatH identified in humans, and NatG has been observed in plants. Nats play critical roles in several cellular processes and integrity and have been suggested as possible drug targets to control different cancer diseases. NatA and NatC have been partially characterized in trypanosomes and shown to be essential for parasite viability. Biologically, the way parasites program their lives is embedded in their unique organelles, metabolic pathways, gene regulation, epigenetic gene activities, and many virulence factors including surface molecules. These characteristics and the different protein-coding genes involved could be Nt-acetylated, and the inhibition of Nats can deny the ability of trypanosomes to survive in any environment because many proteins can be simultaneously affected.

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“…A study that compared sequences between Sylvio X10/1 (lineage 1) and CL Brener (lineage VI) found fewer MASP genes in the former lineage [ 5 ]. Some works have suggested that the similarities and polymorphism found in the members of this family of proteins could allow the identification of up to seven subgroups [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Other reports about these genes showed that proteins are expressed in epimastigotes, trypomastigotes, and amastigotes, and that MASPs can be secreted from parasites during the early stages of amastigogenesis in vitro at pH 5.0 [ 8 , 9 ]. It has also been proposed that the expression profile of these proteins could change during the course of infection and that different strains could differentially express several members of this family [ 6 ]. It has also been shown that immature MASP proteins, as well as the C-terminal portion, can be contained in trypomastigote exovesicles and have immunogenic properties [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, MASPs have immunogenic properties, and some peptides derived from these proteins have been studied as candidates for vaccines against T. cruzi and serological diagnosis [ 17 , 18 , 19 ]. In addition, two subgroups of MASP proteins could be the most immunogenic during the course of infection, at least in a murine model [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Role of a 49 kDa Trypanosoma cruzi Mucin-Associated Surface Protein (MASP49) during the Infection Process and Identification of a Mammalian Cell Surface Receptor

et al. 2023

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Trypanosoma cruzi is the etiologic agent of Chagas disease, a parasitic disease of great medical importance on the American continent. Trypomastigote infection’s initial step in a mammalian host is vital for the parasite’s life cycle. A trypomastigote’s surface presents many molecules, some of which have been proposed to be involved in the infection process, including a glycoprotein family called mucin-associated surface proteins (MASPs). This work describes a 49-kDa molecule (MASP49) that belongs to this family and is expressed mainly on the surfaces of amastigotes and trypomastigotes but can be found in extracts and the membrane-enriched fractions of epimastigotes. This protein is partially GPI-anchored to the surface and has a role during the internalization process, since its blockade with specific antibodies decreases parasite entry into Vero cells by 62%. This work shows that MASP49 binds to peritoneal macrophages and rat cardiomyocytes, undergoes glycosylation via galactose N-acetylgalactosamine, and can attach to the macrophage murine C-type lectin receptor (mMGL). These results suggest that MASP49 can be considered a virulence factor in T. cruzi, and a better understanding of its role in the infection process is necessary.

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Antigenic diversity of MASP gene family of Trypanosoma cruzi

Cited by 3 publications

References 41 publications

The Trypanosoma cruzi Antigen and Epitope Atlas: antibody specificities in Chagas disease patients across the Americas

The Trypanosoma cruzi Antigen and Epitope Atlas: antibody specificities in Chagas disease patients across the Americas

Possible Chemotherapeutic Potential of Inhibiting N-Alpha Terminal Acetylation Activities to Combat Trypanosome Infections

Role of a 49 kDa Trypanosoma cruzi Mucin-Associated Surface Protein (MASP49) during the Infection Process and Identification of a Mammalian Cell Surface Receptor

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