Cargando…

Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3

In our previous studies, we generated a short 13 amino acid antimicrobial peptide (AMP), DM3, showing potent antipneumococcal activity in vitro and in vivo. Here we analyse the underlying mechanisms of action using Next-Generation transcriptome sequencing of penicillin (PEN)-resistant and PEN-suscep...

Descripción completa

Detalles Bibliográficos
Autores principales: Le, Cheng-Foh, Gudimella, Ranganath, Razali, Rozaimi, Manikam, Rishya, Sekaran, Shamala Devi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881017/
https://www.ncbi.nlm.nih.gov/pubmed/27225022
http://dx.doi.org/10.1038/srep26828
_version_ 1782433891424927744
author Le, Cheng-Foh
Gudimella, Ranganath
Razali, Rozaimi
Manikam, Rishya
Sekaran, Shamala Devi
author_facet Le, Cheng-Foh
Gudimella, Ranganath
Razali, Rozaimi
Manikam, Rishya
Sekaran, Shamala Devi
author_sort Le, Cheng-Foh
collection PubMed
description In our previous studies, we generated a short 13 amino acid antimicrobial peptide (AMP), DM3, showing potent antipneumococcal activity in vitro and in vivo. Here we analyse the underlying mechanisms of action using Next-Generation transcriptome sequencing of penicillin (PEN)-resistant and PEN-susceptible pneumococci treated with DM3, PEN, and combination of DM3 and PEN (DM3PEN). DM3 induced differential expression in cell wall and cell membrane structural and transmembrane processes. Notably, DM3 altered the expression of competence-induction pathways by upregulating CelA, CelB, and CglA while downregulating Ccs16, ComF, and Ccs4 proteins. Capsular polysaccharide subunits were downregulated in DM3-treated cells, however, it was upregulated in PEN- and DM3PEN-treated groups. Additionally, DM3 altered the amino acids biosynthesis pathways, particularly targeting ribosomal rRNA subunits. Downregulation of cationic AMPs resistance pathway suggests that DM3 treatment could autoenhance pneumococci susceptibility to DM3. Gene enrichment analysis showed that unlike PEN and DM3PEN, DM3 treatment exerted no effect on DNA-binding RNA polymerase activity but observed downregulation of RpoD and RNA polymerase sigma factor. In contrast to DM3, DM3PEN altered the regulation of multiple purine/pyrimidine biosynthesis and metabolic pathways. Future studies based on in vitro experiments are proposed to investigate the key pathways leading to pneumococcal cell death caused by DM3.
format Online
Article
Text
id pubmed-4881017
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-48810172016-06-08 Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3 Le, Cheng-Foh Gudimella, Ranganath Razali, Rozaimi Manikam, Rishya Sekaran, Shamala Devi Sci Rep Article In our previous studies, we generated a short 13 amino acid antimicrobial peptide (AMP), DM3, showing potent antipneumococcal activity in vitro and in vivo. Here we analyse the underlying mechanisms of action using Next-Generation transcriptome sequencing of penicillin (PEN)-resistant and PEN-susceptible pneumococci treated with DM3, PEN, and combination of DM3 and PEN (DM3PEN). DM3 induced differential expression in cell wall and cell membrane structural and transmembrane processes. Notably, DM3 altered the expression of competence-induction pathways by upregulating CelA, CelB, and CglA while downregulating Ccs16, ComF, and Ccs4 proteins. Capsular polysaccharide subunits were downregulated in DM3-treated cells, however, it was upregulated in PEN- and DM3PEN-treated groups. Additionally, DM3 altered the amino acids biosynthesis pathways, particularly targeting ribosomal rRNA subunits. Downregulation of cationic AMPs resistance pathway suggests that DM3 treatment could autoenhance pneumococci susceptibility to DM3. Gene enrichment analysis showed that unlike PEN and DM3PEN, DM3 treatment exerted no effect on DNA-binding RNA polymerase activity but observed downregulation of RpoD and RNA polymerase sigma factor. In contrast to DM3, DM3PEN altered the regulation of multiple purine/pyrimidine biosynthesis and metabolic pathways. Future studies based on in vitro experiments are proposed to investigate the key pathways leading to pneumococcal cell death caused by DM3. Nature Publishing Group 2016-05-26 /pmc/articles/PMC4881017/ /pubmed/27225022 http://dx.doi.org/10.1038/srep26828 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Le, Cheng-Foh
Gudimella, Ranganath
Razali, Rozaimi
Manikam, Rishya
Sekaran, Shamala Devi
Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3
title Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3
title_full Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3
title_fullStr Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3
title_full_unstemmed Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3
title_short Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3
title_sort transcriptome analysis of streptococcus pneumoniae treated with the designed antimicrobial peptides, dm3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881017/
https://www.ncbi.nlm.nih.gov/pubmed/27225022
http://dx.doi.org/10.1038/srep26828
work_keys_str_mv AT lechengfoh transcriptomeanalysisofstreptococcuspneumoniaetreatedwiththedesignedantimicrobialpeptidesdm3
AT gudimellaranganath transcriptomeanalysisofstreptococcuspneumoniaetreatedwiththedesignedantimicrobialpeptidesdm3
AT razalirozaimi transcriptomeanalysisofstreptococcuspneumoniaetreatedwiththedesignedantimicrobialpeptidesdm3
AT manikamrishya transcriptomeanalysisofstreptococcuspneumoniaetreatedwiththedesignedantimicrobialpeptidesdm3
AT sekaranshamaladevi transcriptomeanalysisofstreptococcuspneumoniaetreatedwiththedesignedantimicrobialpeptidesdm3