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cis-9-Hexadecenal, a Natural Compound Targeting Cell Wall Organization, Critical Growth Factor, and Virulence of Aspergillus fumigatus
[Image: see text] Aspergillus fumigatus causes several nosocomial pulmonary infections and accounts for high morbidity and mortality rate globally. Among various virulence factors, 1,8-dihydroxynaphthalene-melanin plays an important role in the survival during unfavorable conditions both in vivo and...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203908/ https://www.ncbi.nlm.nih.gov/pubmed/32391495 http://dx.doi.org/10.1021/acsomega.0c00615 |
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author | Hoda, Shanu Gupta, Lovely Shankar, Jata Gupta, Alok Kumar Vijayaraghavan, Pooja |
author_facet | Hoda, Shanu Gupta, Lovely Shankar, Jata Gupta, Alok Kumar Vijayaraghavan, Pooja |
author_sort | Hoda, Shanu |
collection | PubMed |
description | [Image: see text] Aspergillus fumigatus causes several nosocomial pulmonary infections and accounts for high morbidity and mortality rate globally. Among various virulence factors, 1,8-dihydroxynaphthalene-melanin plays an important role in the survival during unfavorable conditions both in vivo and in vitro, masks various molecular patterns associated with A. fumigatus, and protects it from the host immune system. In the present study, we aim to understand the potential of cis-9-hexadecenal as an antimelanogenic compound and its role in modulating other associated virulence factors in A. fumigatus. cis-9-Hexadecenal is a bioactive compound that belongs to C(16) mono-unsaturated fatty-aldehyde groups. Minimum effective concentration of cis-9-hexadecenal affecting A. fumigatus melanin biosynthesis was determined using broth microdilution method. The spectrophotometric analysis revealed reduced melanin content (91%) and hydrophobicity (59%) at 0.293 mM of cis-9-hexadecenal. Cell surface organizational changes using electron microscopy showed altered demelanized smooth A. fumigatus conidial surface without any protrusions after cis-9-hexadecenal treatment. The transcript analysis of polyketide synthase (PKS) pksP/alb1 gene was quantified through qRT-PCR which revealed an upregulated expression. Total proteome profiling conducted through LC-MS-MS showed upregulated PKS enzyme but other downstream proteins involved in the 1,8-dihydroxynaphthalene-melanin biosynthesis pathway were absent. The homology modeling of PKS using Expasy’s web server predicted that PKS is stable at varied conditions and is hydrophilic in nature. The Ramachandran plot by PROCHECK confirmed the 3-D structure of PKS to be reliable. Docking analysis using AutoDock-4.2.6 predicted the binding of cis-9-hexadecenal and PKS at Thr-264 and Ser-171 residue via hydrogen bonding at a low binding energy of −4.95 kcal/mol. |
format | Online Article Text |
id | pubmed-7203908 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-72039082020-05-08 cis-9-Hexadecenal, a Natural Compound Targeting Cell Wall Organization, Critical Growth Factor, and Virulence of Aspergillus fumigatus Hoda, Shanu Gupta, Lovely Shankar, Jata Gupta, Alok Kumar Vijayaraghavan, Pooja ACS Omega [Image: see text] Aspergillus fumigatus causes several nosocomial pulmonary infections and accounts for high morbidity and mortality rate globally. Among various virulence factors, 1,8-dihydroxynaphthalene-melanin plays an important role in the survival during unfavorable conditions both in vivo and in vitro, masks various molecular patterns associated with A. fumigatus, and protects it from the host immune system. In the present study, we aim to understand the potential of cis-9-hexadecenal as an antimelanogenic compound and its role in modulating other associated virulence factors in A. fumigatus. cis-9-Hexadecenal is a bioactive compound that belongs to C(16) mono-unsaturated fatty-aldehyde groups. Minimum effective concentration of cis-9-hexadecenal affecting A. fumigatus melanin biosynthesis was determined using broth microdilution method. The spectrophotometric analysis revealed reduced melanin content (91%) and hydrophobicity (59%) at 0.293 mM of cis-9-hexadecenal. Cell surface organizational changes using electron microscopy showed altered demelanized smooth A. fumigatus conidial surface without any protrusions after cis-9-hexadecenal treatment. The transcript analysis of polyketide synthase (PKS) pksP/alb1 gene was quantified through qRT-PCR which revealed an upregulated expression. Total proteome profiling conducted through LC-MS-MS showed upregulated PKS enzyme but other downstream proteins involved in the 1,8-dihydroxynaphthalene-melanin biosynthesis pathway were absent. The homology modeling of PKS using Expasy’s web server predicted that PKS is stable at varied conditions and is hydrophilic in nature. The Ramachandran plot by PROCHECK confirmed the 3-D structure of PKS to be reliable. Docking analysis using AutoDock-4.2.6 predicted the binding of cis-9-hexadecenal and PKS at Thr-264 and Ser-171 residue via hydrogen bonding at a low binding energy of −4.95 kcal/mol. American Chemical Society 2020-04-21 /pmc/articles/PMC7203908/ /pubmed/32391495 http://dx.doi.org/10.1021/acsomega.0c00615 Text en Copyright © 2020 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
spellingShingle | Hoda, Shanu Gupta, Lovely Shankar, Jata Gupta, Alok Kumar Vijayaraghavan, Pooja cis-9-Hexadecenal, a Natural Compound Targeting Cell Wall Organization, Critical Growth Factor, and Virulence of Aspergillus fumigatus |
title | cis-9-Hexadecenal, a Natural Compound
Targeting Cell Wall Organization, Critical Growth Factor, and Virulence
of Aspergillus fumigatus |
title_full | cis-9-Hexadecenal, a Natural Compound
Targeting Cell Wall Organization, Critical Growth Factor, and Virulence
of Aspergillus fumigatus |
title_fullStr | cis-9-Hexadecenal, a Natural Compound
Targeting Cell Wall Organization, Critical Growth Factor, and Virulence
of Aspergillus fumigatus |
title_full_unstemmed | cis-9-Hexadecenal, a Natural Compound
Targeting Cell Wall Organization, Critical Growth Factor, and Virulence
of Aspergillus fumigatus |
title_short | cis-9-Hexadecenal, a Natural Compound
Targeting Cell Wall Organization, Critical Growth Factor, and Virulence
of Aspergillus fumigatus |
title_sort | cis-9-hexadecenal, a natural compound
targeting cell wall organization, critical growth factor, and virulence
of aspergillus fumigatus |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203908/ https://www.ncbi.nlm.nih.gov/pubmed/32391495 http://dx.doi.org/10.1021/acsomega.0c00615 |
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