|
|
GEO help: Mouse over screen elements for information. |
|
Status |
Public on Mar 29, 2018 |
Title |
Collateral sensitivity of antibiotic resistant bacteria to antimicrobial peptides |
Organism |
Escherichia coli |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
Cationic antimicrobial peptides (CAPs) are promising novel alternatives to conventional antibacterial agents, but the overlap in resistance mechanisms between small-molecule antibiotics and CAPs is unknown. Does evolution of antibiotic resistance decrease (cross-resistance) or increase (collateral sensitivity) susceptibility to CAPs? We systematically addressed this issue by studying the susceptibilities of a comprehensive set of antibiotic resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic resistant bacteria frequently showed collateral sensitivity to CAPs, while cross-resistance was relatively rare. We identified clinically relevant multidrug resistance mutations that simultaneously elevate susceptibility to certain CAPs. Transcriptome and chemogenomic analysis revealed that such mutations frequently alter the lipopolysaccharide composition of the outer cell membrane and thereby increase the killing efficiency of membrane-interacting antimicrobial peptides. Furthermore, we identified CAP-antibiotic combinations that rescue the activity of existing antibiotics and slow down the evolution of resistance to antibiotics. Our work provides a proof of principle for the development of peptide based antibiotic adjuvants that enhance antibiotic action and block evolution of resistance.
|
|
|
Overall design |
84 samples were collected from Escherichia coli lines adapted to one of 12 antibiotics as well as from non-adapted controls. Two parallel lines for each antibiotic were included in the assay. Sample groups contain 3 biological replicates.
|
|
|
Contributor(s) |
Lazar V, Martins A, Spohn R, Daruka L, Fekete G, Grezal G, Szamel M, Jangir PK, Kintses B, Csorgo B, Gyorkei A, Kincses A, Der A, Walter FR, Deli MA, Hegedus Z, Olajos G, Mehi O, Balint B, Nagy I, Martinek TA, Papp B, Pal C |
Citation(s) |
29795541 |
|
Submission date |
Mar 16, 2017 |
Last update date |
May 15, 2019 |
Contact name |
Balazs Balint |
E-mail(s) |
balintb@seqomics.hu
|
Phone |
0036304276152
|
Organization name |
Seqomics Ltd
|
Street address |
Vallalkozok street
|
City |
7 |
State/province |
Csongrad |
ZIP/Postal code |
6782 |
Country |
Hungary |
|
|
Platforms (1) |
GPL23187 |
AB 5500xl Genetic Analyzer (Escherichia coli) |
|
Samples (84)
|
|
Relations |
BioProject |
PRJNA379428 |
SRA |
SRP102011 |
Supplementary file |
Size |
Download |
File type/resource |
GSE96706_RAW.tar |
6.0 Mb |
(http)(custom) |
TAR (of CSV) |
GSE96706_scaled.voom_quantile.combat.xlsx |
4.6 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
Processed data are available on Series record |
|
|
|
|
|