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Series GSE96706 Query DataSets for GSE96706
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)
GSM2538622 1A
GSM2538623 1B
GSM2538624 1C
Relations
BioProject PRJNA379428
SRA SRP102011

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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 SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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