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

Cheng Foh Le, Ranganath Gudimella, Rozaimi Mohamad Razali, Rishya Manikam, Shamala Devi Sekaran

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number26828
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 26 May 2016
Externally publishedYes

Fingerprint

Gene Expression Profiling
Streptococcus pneumoniae
Penicillins
Peptides
Down-Regulation
DNA-Directed RNA Polymerases
Sigma Factor
Amino Acids
Ribosome Subunits
Adenosine Monophosphate
Metabolic Networks and Pathways
Transcriptome
Mental Competency
Cell Wall
Polysaccharides
Cell Death
Cell Membrane
DNA
Genes
Proteins

ASJC Scopus subject areas

  • General

Cite this

Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3. / Le, Cheng Foh; Gudimella, Ranganath; Mohamad Razali, Rozaimi; Manikam, Rishya; Sekaran, Shamala Devi.

In: Scientific Reports, Vol. 6, 26828, 26.05.2016.

Research output: Contribution to journalArticle

Le, Cheng Foh ; Gudimella, Ranganath ; Mohamad Razali, Rozaimi ; Manikam, Rishya ; Sekaran, Shamala Devi. / Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3. In: Scientific Reports. 2016 ; Vol. 6.
@article{de00c4c46b584dcba31a6f8637813b1f,
title = "Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3",
abstract = "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.",
author = "Le, {Cheng Foh} and Ranganath Gudimella and {Mohamad Razali}, Rozaimi and Rishya Manikam and Sekaran, {Shamala Devi}",
year = "2016",
month = "5",
day = "26",
doi = "10.1038/srep26828",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3

AU - Le, Cheng Foh

AU - Gudimella, Ranganath

AU - Mohamad Razali, Rozaimi

AU - Manikam, Rishya

AU - Sekaran, Shamala Devi

PY - 2016/5/26

Y1 - 2016/5/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84971260997&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84971260997&partnerID=8YFLogxK

U2 - 10.1038/srep26828

DO - 10.1038/srep26828

M3 - Article

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 26828

ER -