Comparative Genomics of Histoplasma capsulatum and Prediction of New Vaccines and Drug Targets

Almeida, Paula Cristina Silva; Roque, Bruno Stelmastchuk; Felice, Andrei Giacchetto; Jaiswal, Arun Kumar; Tiwari, Sandeep; Azevedo, Vasco; Silva‐Vergara, Mario León; Soares, Siomar de Castro; Ferreira-Paim, Kennio; Fonseca, Fernanda Machado

doi:10.3390/jof9020193

Cited by 5 publications

(3 citation statements)

References 78 publications

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“… Morin et al (2019) highlights the genetic specificity of Glomeromycotina by comparative genomics. Almeida et al (2023) compared and analyzed the genomes of 4 strains of Clostridium perfringens , predicted potential protein target sites that can be used to construct vaccines and carried out molecular docking on the identified target sites, which is helpful for the development of new vaccines and drugs. In this experiment, in order to explore the special cold adaptation mechanism evolved by P. fragi D12 under long-term low-temperature stress, we conducted a comparative genetic study on five strains of P. fragi (A13BB, DBC, NL20W, NMC25, and NRRLB727) ( Singha et al, 2017 ; Awolope et al, 2021 ; Wu J. et al, 2022 ) with different origins but the closest homology.…”

Section: Resultsmentioning

confidence: 99%

Mining of key genes for cold adaptation from Pseudomonas fragi D12 and analysis of its cold-adaptation mechanism

Bao

Xin

et al. 2023

Front. Microbiol.

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The psychrotroph Pseudomonas fragi D12, which grew strongly under low temperatures, was screened from tundra soil collected from the permanent alpine zone on Changbai Mountain. To mine the genes critical for cold tolerance and to investigate the cold-adaptation mechanism, whole-genome sequencing, comparative genomic analysis, and transcriptome analysis were performed with P. fragi. A total of 124 potential cold adaptation genes were identified, including nineteen unique cold-adaptive genes were detected in the genome of P. fragi D12. Three unique genes associated with pili protein were significantly upregulated at different degrees of low temperature, which may be the key to the strong low-temperature adaptability of P. fragi D12. Meanwhile, we were pleasantly surprised to find that Pseudomonas fragi D12 exhibited different cold-adaptation mechanisms under different temperature changes. When the temperature declined from 30°C to 15°C, the response included maintenance of the fluidity of cell membranes, increased production of extracellular polymers, elevation in the content of compatibility solutes, and reduction in the content of reactive oxygen species, thereby providing a stable metabolic environment. When the temperature decreased from 15°C to 4°C, the response mainly included increases in the expression of molecular chaperones and transcription factors, enabling the bacteria to restore normal transcription and translation. The response mechanism of P. fragi D12 to low-temperature exposure is discussed. The results provide new ideas for the cold-adaptation mechanism of cold-tolerant microorganisms.

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Section: Resultsmentioning

confidence: 99%

Mining of key genes for cold adaptation from Pseudomonas fragi D12 and analysis of its cold-adaptation mechanism

Bao

Xin

et al. 2023

Front. Microbiol.

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“…The latest research in this field, approaching revolutionary methods of reverse vaccinology, comparative genomics, and molecular docking, have identified some candidate targets to produce both vaccines and new drugs against H. capsulatum. The most promising candidate vaccine target appears to be beta-1,3-glucanosyl transferase, the enzyme involved in the elongation of beta-(1-3)-glucans in the fungal cell wall, but further in vivo research is needed to test its efficacy and safety [143].…”

Section: Specific Preventionmentioning

confidence: 99%

Epidemiology of Histoplasmosis

Efrim¹,

Dumea²,

Cernat³

2023

Infectious Diseases

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More prevalent than initially considered, histoplasmosis is primarily a non-contagious disease of the reticuloendothelial system, producing a broad spectrum of clinical manifestations, ranging from asymptomatic or self-limited infection, in immunocompetent patients to life-threatening, disseminated disease in immunocompromised ones. The causative agent is H. capsulatum, a thermally dimorphic, intracellular fungus, discovered in 1906, by the pathologist Samuel Darling, when examined tissues from a young man whose death was mistakenly attributed to miliary tuberculosis. Since then, histoplasmosis was described on six continents, with high and low endemicity areas. H. capsulatum is a soil-based fungus, commonly associated with river valleys in the temperate zone, and with the presence of bird and bat guano. Infection occurs when saprophytic spores are inhaled and change to the pathogenic yeast in the lungs, where H. capsulatum overcomes many obstacles to cause host injuries. Depending on geographic distribution, morphology, and clinical symptoms, three varieties have been historically recognized, two of them (var. capsulatum and var. duboisii) being pathogen to humans, and the third (var. farciminosum) has predominantly been described as an equine pathogen. In endemic areas, patients with AIDS or people who receive immunosuppressive therapies should be counseled to avoid high-risk activities; otherwise, precautionary measures should be taken.

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“…In contrast to previous studies limited to one (Mandal and Sinha, 2021; Dineshkumar and Antony, 2022), or two computational methods (Subramanian et al, 2022), the present study employs a consensus approach from eight distinct computational tools, including Arti cial Intelligence (AI) and deep learning, to enhance the precision of protein location prediction. Recognizing the signi cance of cytoplasmic proteins as suitable targets for pathogens (Almeida et al, 2023;Sabzi et al, 2023), only proteins predicted to reside in the cytoplasm, as indicated by the consensus, were considered for subsequent analysis.…”

Section: Target Prioritization Protein Localization Predictionmentioning

confidence: 99%

Comparative Omics Analysis for Novel Target Discovery in Plant Pathogens: A Case Study for Magnaporthe oryzae

Luthfi,

Piapukiew,

Pandey

et al. 2023

Preprint

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The central concern surrounding chemical pesticide application is its potential adverse effects on non-target organisms. For fungal pathogens, the search for specific targets has been complicated by the similarities in pathways shared between these pathogens and humans. We present a comprehensive strategy, integrating comparative omics and bioinformatics, to pinpoint precise targets for fungicides effective against the fungal pathogen Magnaporthe oryzae(M. oryzae), responsible for rice blast disease. Our approach involves subtractive metabolic pathways, homology screening and target prioritization. Through subtractive metabolic analysis, we identified three unique M. oryzaepathways, distinct from human and rice. Non-redundant protein sequences were subsequently subjected to BLASTP screening against human and rice, as well as other databases from diverse organisms. Target subcellular localization was predicted using eight tools, including Artificial Intelligence and a deep learning method. A comprehensive examination of biological processes was conducted, including gene expression, protein-protein interactions, network enrichment, broad-spectrum activity, and physicochemical analysis. Glutamate 5-kinase (G5K) emerged as the prime candidate for targeted fungicide development, promising progress in precision-oriented solutions.

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Comparative Genomics of Histoplasma capsulatum and Prediction of New Vaccines and Drug Targets

Cited by 5 publications

References 78 publications

Mining of key genes for cold adaptation from Pseudomonas fragi D12 and analysis of its cold-adaptation mechanism

Mining of key genes for cold adaptation from Pseudomonas fragi D12 and analysis of its cold-adaptation mechanism

Epidemiology of Histoplasmosis

Comparative Omics Analysis for Novel Target Discovery in Plant Pathogens: A Case Study for Magnaporthe oryzae

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