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| Status |
Public on Oct 01, 2012 |
| Title |
Additional Routes to Staphylococcus aureus Daptomycin Resistance as Revealed by Comparative Genome Sequencing, Transcriptional Profiling, and Phenotypic Studies |
| Organism |
Staphylococcus aureus |
| Experiment type |
Expression profiling by array
|
| Summary |
Daptomycin is an extensively used anti-staphylococcal agent due to the rise in methicillin-resistant Staphylococcus aureus. However, both laboratory-derived and clinical decreased susceptibility isolates have been described, but the mechanism(s) of resistance is poorly understood. To further understand daptomycin resistance, comparative genome sequencing, transcriptomics, ultrastructure ,and cell envelope studies were carried out on two relatively higher level (4 and 8 ug/ml-1) laboratory-derived daptomycin-resistant strains (strains CB1541 and CB1540 respectively) compared to their methicillin-resistant parent strain (CB1118;MW2). Genes altered in their expression common to both transcriptomes included some involved in glycine betaine accumulation, mscL, ure genes, femH, spa and smpB. However, the CB1541 transcriptome was further characterized by upregulation of various heat shock chaperone and protease genes, consistent with a mutation in clpP, and lytM and sceD. Both strains showed slow growth, and strongly decreased autolytic activity that appeared to be mainly due to decreased autolysin production. In contrast to previous common findings, we did not find any mutations in phospholipid biosynthesis genes, and it appears there are multiple pathways to and factors in daptomycin resistance.
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| Overall design |
MHB cultures (biological replicates: N=3) were then grown to exponential phase (OD600=0.4). Dye-swapping was performed between samples.
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| Contributor(s) |
Song Y |
| Citation(s) |
23554895 |
| |
| Submission date |
Sep 10, 2012 |
| Last update date |
Apr 05, 2013 |
| Contact name |
Arunachalam Muthaiyan, Brian Wilkinson |
| E-mail(s) |
[email protected], [email protected]
|
| Phone |
309-438-7244
|
| URL |
http://www.bio.ilstu.edu/Wilkinson/
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| Organization name |
Illinois State University
|
| Department |
Biological Sciences
|
| Lab |
Microbiology
|
| Street address |
Julian Hall
|
| City |
Normal |
| State/province |
IL |
| ZIP/Postal code |
61790 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL5881 |
JCVI PFGRC Staphylococcus aureus 22K v6 array designed primarily based on strain MW2 |
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| Samples (6)
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| GSM1000724 |
daptomycin resistant strain CB1540 vs. parent strain CB1118-rep1 |
| GSM1000725 |
daptomycin resistant strain CB1540 vs. parent strain CB1118-rep2 |
| GSM1000726 |
daptomycin resistant strain CB1540 vs. parent strain CB1118-rep3 |
| GSM1000727 |
daptomycin resistant strain CB1541 vs. parent strain CB1118-rep1 |
| GSM1000728 |
daptomycin resistant strain CB1541 vs. parent strain CB1118-rep2 |
| GSM1000729 |
daptomycin resistant strain CB1541 vs. parent strain CB1118-rep3 |
|
| Relations |
| BioProject |
PRJNA174813 |
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