Participation of<i>Trypanosoma cruzi</i>gp63 molecules on the interaction with<i>Rhodnius prolixus</i>

Rebello, Karina M.; Uehara, Lívia Almeida; Ennes-Vidal, Vítor; Garcia-Gomes, Aline S.; Britto, Constança; Menna-Barreto, Rubem F. S.; Santos, André Luis Souza dos; Branquinha, Marta H.; d’Avila-Levy, Claudia M.

doi:10.1017/s0031182019000441

Cited by 15 publications

(13 citation statements)

References 51 publications

(75 reference statements)

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“…Cuevas et al have reported that the Tcgp63-I, is expressed in the different parasite stages, but a very low metalloprotease activity in epimastigotes extracts was observed by zymography, using 250 × 10 6 parasites [ 48 ]. In agreement, Rebello et al also observed gp63 gelatinolytic activity in epimastigotes stage extracts [ 49 ]. It is important to note, that the maximum number of circulating parasites of samples that we analyzed, were 4 × 10 6 mL −1 (Cvd strain) and 3,5 × 10 6 mL −1 (Ac strain), ( Fig.…”

Section: Discussionsupporting

confidence: 78%

Sialic acid removal by trans-sialidase modulates MMP-2 activity during Trypanosoma cruzi infection

et al. 2021

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Matrix metalloproteinases (MMPs) not only play a relevant role in homeostatic processes but are also involved in several pathological mechanisms associated with infectious diseases. As their clinical relevance in Chagas disease has recently been highlighted, we studied the modulation of circulating MMPs by Trypanosoma cruzi infection. We found that virulent parasites from Discrete Typing Units (DTU) VI induced higher proMMP-2 and MMP-2 activity in blood, whereas both low (DTU I) and high virulence parasites induced a significant decrease in proMMP-9 plasma activity. Moreover, trans -sialidase, a relevant T. cruzi virulence factor, is involved in MMP-2 activity modulation both in vivo and in vitro. It removes α2,3-linked sialyl residues from cell surface glycoconjugates, which then triggers the PKC/MEK/ERK signaling pathway. Additionally, bacterial sialidases specific for this sialyl residue linkage displayed similar MMP modulation profiles and triggered the same signaling pathways. This novel pathogenic mechanism, dependent on sialic acid removal by the neuraminidase activity of trans -sialidase, can be exploited by different pathogens expressing sialidases with similar specificity. Thus, here we present a new pathogen strategy through the regulation of the MMP network.

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Section: Discussionsupporting

confidence: 78%

Sialic acid removal by trans-sialidase modulates MMP-2 activity during Trypanosoma cruzi infection

et al. 2021

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“…The surface protease gp63 is a very well-known protease from T. cruzi important for host cell infection ( Kulkarni et al., 2009 ) and presents metalloprotease activity ( Cuevas et al., 2003 ). In our gelatin zymography assays, we observed gelatinolytic activity that could be related to the presence of gp63, since the negative bands presented a size between 45 and 66 kDa ( Rebello et al., 2019 ).…”

Section: Discussionmentioning

confidence: 88%

Biological and Molecular Effects of Trypanosoma cruzi Residence in a LAMP-Deficient Intracellular Environment

Oliveira

Rezende

Gorshkov

et al. 2022

Front. Cell. Infect. Microbiol.

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Trypanosoma cruzi invades non-professional phagocytic cells by subverting their membrane repair process, which is dependent on membrane injury and cell signaling, intracellular calcium increase, and lysosome recruitment. Cells lacking lysosome-associated membrane proteins 1 and 2 (LAMP1 and LAMP2) are less permissive to parasite invasion but more prone to parasite intracellular multiplication. Several passages through a different intracellular environment can significantly change T. cruzi’s gene expression profile. Here, we evaluated whether one single passage through LAMP-deficient (KO) or wild-type (WT) fibroblasts, thus different intracellular environments, could influence T. cruzi Y strain trypomastigotes’ ability to invade L6 myoblasts and WT fibroblasts host cells. Parasites released from LAMP2 KO cells (TcY-L2−/−) showed higher invasion, calcium signaling, and membrane injury rates, for the assays in L6 myoblasts, when compared to those released from WT (TcY-WT) or LAMP1/2 KO cells (TcY-L1/2−/−). On the other hand, TcY-L1/2−/− showed higher invasion, calcium signaling, and cell membrane injury rates, for the assays in WT fibroblasts, compared to TcY-WT and TcY-L1/2−/−. Albeit TcY-WT presented an intermediary invasion and calcium signaling rates, compared to the others, in WT fibroblasts, they induced lower levels of injury, which reinforces that signals mediated by surface membrane protein interactions also have a significant contribution to trigger host cell calcium signals. These results clearly show that parasites released from WT or LAMP KO cells are distinct from each other. Additionally, these parasites’ ability to invade the cell may be distinct depending on which cell type they interact with. Since these alterations most likely would reflect differences among parasite surface molecules, we also evaluated their proteome. We identified few protein complexes, membrane, and secreted proteins regulated in our dataset. Among those are some members of MASP, mucins, trans-sialidases, and gp63 proteins family, which are known to play an important role during parasite infection and could correlate to TcY-WT, TcY-L1/2−/−, and TcY-L2−/− biological behavior.

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“…The 63 kDa glycoprotein (gp63), another widely studied Leishmania virulence factor, encoded by a multigene family highly expanded in T. cruzi genome ( El-Sayed, 2005 ), may contribute to the parasite’s virulence in the insect stage via its metalloprotease activity ( Cuevas et al., 2003 ). A study has also shown the participation of gp63 in the parasite’s adhesion to Rhodnius prolixus midgut via assays using divalent metal chelators or anti-Tcgp63-I antibodies caused an impaired T. cruzi adhesion to the vector midgut ( Rebello et al., 2019 ).…”

Section: Virulence Factors In Insectsmentioning

confidence: 99%

“…Despite it has been hard to obtain direct evidence of the protein’s nutritional role in insects, the adhesion events have been widely demonstrated both in monoxenous trypanosomatids, e.g., Crithidia guilhermei ( D’Avila-Levy et al., 2006a ), Leptomonas spp. ( Pereira et al., 2009 ), Angomonas deanei ( D’Avila-Levy et al., 2008 ) and Herpetomonas muscarum ( Nogueira de Melo et al., 2006 ); and dixenous trypanosomatids, e.g., Phytomonas serpens ( D’Avila-Levy et al., 2006b ), T. cruzi ( Rebello et al., 2019 ) and Leishmania spp. ( Soares et al., 2017 ).…”

Section: Virulence Factors In Insectsmentioning

confidence: 99%

Role of Virulence Factors of Trypanosomatids in the Insect Vector and Putative Genetic Events Involved in Surface Protein Diversity

Neto

Silveira

Mortara

2022

Front. Cell. Infect. Microbiol.

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Trypanosomatids are flagellate protozoans that can infect several invertebrate and vertebrate hosts, including insects and humans. The three most studied species are the human pathogens Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. which are the causative agents of Human African Trypanosomiasis (HAT), Chagas disease and different clinical forms of leishmaniasis, respectively. These parasites possess complex dixenous life cycles, with zoonotic and anthroponotic stages, and are transmitted by hematophagous insects. To colonize this myriad of hosts, they developed mechanisms, mediated by virulence factors, to infect, propagate and survive in different environments. In insects, surface proteins play roles in parasite attachment and survival in the insect gut, whilst in the mammalian host, the parasites have a whole group of proteins and mechanisms that aid them invading the host cells and evading its immune system components. Many studies have been done on the impact of these molecules in the vertebrate host, however it is also essential to notice the importance of these virulence factors in the insect vector during the parasite life cycle. When inside the insect, the parasites, like in humans, also need to survive defense mechanisms components that can inhibit parasite colonization or survival, e.g., midgut peritrophic membrane barrier, digestive enzymes, evasion of excretion alongside the digested blood meal, anatomic structures and physiological mechanisms of the anterior gut. This protection inside the insect is often implemented by the same group of virulence factors that perform roles of immune evasion in the mammalian host with just a few exceptions, in which a specific protein is expressed specifically for the insect vector form of the parasite. This review aims to discuss the roles of the virulence molecules in the insect vectors, showing the differences and similarities of modes of action of the same group of molecules in insect and humans, exclusive insect molecules and discuss possible genetic events that may have generated this protein diversity.

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Participation ofTrypanosoma cruzigp63 molecules on the interaction withRhodnius prolixus

Cited by 15 publications

References 51 publications

Sialic acid removal by trans-sialidase modulates MMP-2 activity during Trypanosoma cruzi infection

Sialic acid removal by trans-sialidase modulates MMP-2 activity during Trypanosoma cruzi infection

Biological and Molecular Effects of Trypanosoma cruzi Residence in a LAMP-Deficient Intracellular Environment

Role of Virulence Factors of Trypanosomatids in the Insect Vector and Putative Genetic Events Involved in Surface Protein Diversity

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