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In Silico Structural and Functional Characterization of HtrA Proteins of Leptospira spp.: Possible Implications in Pathogenesis.

ABSTRACT: Leptospirosis is a zoonosis caused by the pathogenic bacteria of the genus Leptospira. The identification of conserved outer membrane proteins among pathogenic strains is a major research target in elucidating mechanisms of pathogenicity. Surface-exposed proteins are most probably the ones involved in the interaction of leptospires with the environment. Some spirochetes use outer membrane proteases as a way to penetrate host tissues. HtrA is a family of proteins found in various cell types, from prokaryotes to primates. They are a set of proteases usually composed of a serine protease and PDZ domains, and they are generally transported to the periplasm. Here, we identified four genes-annotated as HtrA, LIC11111, LIC20143, LIC20144 and LIC11037-and another one annotated as a serine protease, LIC11112. It is believed that the last forms a functional heterodimer with LIC11111, since they are organized in one operon. Our analyses showed that these proteins are highly conserved among pathogenic strains. LIC11112, LIC20143, and LIC11037 have the serine protease domain with the conserved catalytic triad His-Asp-Ser. This is the first bioinformatics analysis of HtrA proteins from Leptospira that suggests their proteolytic activity potential. Experimental studies are warranted to elucidate this possibility.

SUBMITTER: Daroz BB

PROVIDER: S-EPMC7709667 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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In Silico Structural and Functional Characterization of HtrA Proteins of <i>Leptospira</i> spp.: Possible Implications in Pathogenesis.

Daroz Brenda Bevilaqua BB Fernandes Luis Guilherme Virgílio LGV Teixeira Aline Florencio AF Nascimento Ana Lucia Tabet Oller ALTO

Tropical medicine and infectious disease 20201128 4

Leptospirosis is a zoonosis caused by the pathogenic bacteria of the genus <i>Leptospira</i>. The identification of conserved outer membrane proteins among pathogenic strains is a major research target in elucidating mechanisms of pathogenicity. Surface-exposed proteins are most probably the ones involved in the interaction of leptospires with the environment. Some spirochetes use outer membrane proteases as a way to penetrate host tissues. HtrA is a family of proteins found in various cell type ...[more]

PMID: 33260771

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Project description:Burkitt lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL (eBL) in developing countries, necessitating new strategies. The normal germinal center B cell is the presumed cell of origin for both BL and diffuse large B cell lymphoma (DLBCL), yet gene expression analysis suggests that these malignancies may utilize different oncogenic pathways. BL is subdivided into a sporadic subtype (sBL) that is diagnosed in developed countries, the EBV-associated eBL subtype, and an HIV-associated subtype (hivBL), but it is unclear whether these subtypes employ similar or divergent oncogenic mechanisms. Here we used high throughput RNA sequencing and RNA interference screening to discover essential regulatory pathways that cooperate with MYC, the defining oncogene of this cancer. In 70% of sBL cases, mutations affecting the transcription factor TCF3 (E2A) or its negative regulator ID3 fostered TCF3 dependency. TCF3 activated the pro-survival PI(3) kinase pathway in BL, in part by augmenting tonic B cell receptor signaling. In 38% of sBL cases, oncogenic CCND3 mutations produced highly stable cyclin D3 isoforms that drive cell cycle progression. These findings suggest opportunities to improve therapy for patients with BL. Gene expression was analyzed using Agilent human 4X44K oligo gene expression arrays. Cell lines (Namalwa, BL41, Daudi, Defauw, and THOMAS) were infected with control (empty vector, Cy3) paired with ID3 (Cy5) or control (shControl, Cy3) paired with shTCF3 (Cy5) constructs, and changes in gene expression were monitored over time after induction of the constructs with doxycyclin. In Namalwa (n=8) and THOMAS (n=4) cell lines, a four timepoint series (24, 48, 72, 96 hours) of construct induction was analyzed, for a total of 12 arrays. In BL41 (n=4), Daudi (n=4) and Defauw (n=4) cell lines, a two timepoint series (24 and 48 hours) of construct induction was analyzed, for a total of 12 arrays. In addition, two cell lines (Daudi and THOMAS) were treated with Rapamycin (100 pM) and paired with a DMSO control in a four timepoint series (3, 6, 12 and 24 hours) for a total of 8 arrays.

Dataset Information

In Silico Structural and Functional Characterization of HtrA Proteins of Leptospira spp.: Possible Implications in Pathogenesis.

Publications

In Silico Structural and Functional Characterization of HtrA Proteins of <i>Leptospira</i> spp.: Possible Implications in Pathogenesis.

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