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Further Insights into the Mode of Action of the Lipoglycopeptide Telavancin through Global Gene Expression Studies

ABSTRACT: Background: Telavancin is a novel semi-synthetic lipoglycopeptide derivative of vancomycin with a decylaminoethyl side chain that is active against Gram-positive bacteria including Staphylococcus aureus strains resistant to methicillin or vancomycin. This study describes transcriptome alterations in S. aureus strain ATCC29213 treated with telavancin for 15 min and 60 min in comparing with other agents treatment, including vancomycin, enduracidin, m-chlorophenylhydrazone.

ORGANISM(S): Staphylococcus aureus

PROVIDER: GSE37272 | GEO | 2012/04/14

SECONDARY ACCESSION(S): PRJNA159219

REPOSITORIES: GEO

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Further Insights into the Mode of Action of the Lipoglycopeptide Telavancin through Global Gene Expression Studies

Project description:Background: Telavancin is a novel semi-synthetic lipoglycopeptide derivative of vancomycin with a decylaminoethyl side chain that is active against Gram-positive bacteria including Staphylococcus aureus strains resistant to methicillin or vancomycin. This study describes transcriptome alterations in S. aureus strain ATCC29213 treated with telavancin for 15 min and 60 min in comparing with other agents treatment, including vancomycin, enduracidin, m-chlorophenylhydrazone. MHB cultures (biological replicates: N=3) were then grown to exponential phase (OD580=0.35) before the addition of telavancin(8 M-BM-5g/ml final concentration), or vancomycin (10 /M-BM-5g ml) or CCCP (2 M-BM-5g/ ml ); or enduracidin (1 M-BM-5g ml) and incubated for an additional 15 min , and 60 min before sampling. Dye-swapping was performed between samples.

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Project description:Coordinated protein-coding sequence transcriptional responses of Staphylococcus aureus to antimicrobial exposure are well described but little is known of the role of bacterial non-coding, small RNAs (sRNAs) in these responses. Here we used RNAseq to investigate the sRNA response of the epidemic multiresistant hospital ST239 S. Aureus strain JKD6009 and its vancomycin-intermediate clinical derivative, JKD6008, after exposure to four antibiotics representing the major classes of antimicrobials used to treat methicillin-resistant S. Aureus infections. These agents included vancomycin, linezolid, ceftobiprole, and tigecycline. We identified 410 potential sRNAs (sRNAs) and then compared global sRNA and mRNA expression profiles at 2 and 6 hours, without antibiotic exposure, and after exposure to 0.5 x MIC for each antibiotic, for both JKD6009 (VSSA), and JKD6008 (VISA). Two strains were used (JKD6009, vancomycin-susceptible S. Aureus; JKD6008, in vivo derived vancomycin-intermediate S. Aureus). The complete JKD6008 genome seqeuce was used as the reference. Two time points, 2 hours and 6 hours after culture in Mueller Hinton broth. Strains were exposed to no antibiotic, or 0.5 x MIC for 10 mins for the following antibiotics; vancomycin, linezolid, ceftobiprole, tigecycline. RNA isolation procedures enriched for mRNA or sRNA. The 40 cDNA libraries were sequenced using a whole flowcell (8 lanes) in an Illumina genome analyzer GAII for 36 cycles. Data was analyzed using the BioConductor package limma, and by applying non-negative matrix factorization to determine the impact of antibiotic exposure on the sRNA and mRNA transcriptional profiles.

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