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| Status |
Public on Jan 06, 2017 |
| Title |
Toxin mediates sepsis caused by methicillin-resistant Staphylococcus epidermidis |
| Platform organisms |
Coxiella burnetii; Rickettsia rickettsii; Chlamydia muridarum; Chlamydia pneumoniae AR39; Staphylococcus epidermidis RP62A; Staphylococcus epidermidis ATCC 12228; Staphylococcus aureus subsp. aureus MW2; Borreliella burgdorferi B31; Coxiella burnetii RSA 493; Chlamydia caviae GPIC; Chlamydia trachomatis D/UW-3/CX; Staphylococcus haemolyticus JCSC1435; Granulibacter bethesdensis |
| Sample organism |
Staphylococcus epidermidis |
| Experiment type |
Expression profiling by array
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| Summary |
Bacterial sepsis is a major killer in hospitalized patients. Coagulase-negative staphylococci (CNS) with the leading species Staphylococcus epidermidis are the most frequent causes of nosocomial sepsis, with most infectious isolates being methicillin resistant. However, which bacterial factors underlie the pathogenesis of CNS sepsis is unknown. While it has been commonly believed that invariant structures on the surface of CNS trigger sepsis by causing an over-reaction of the immune system, we show here that sepsis caused my methicillin-resistant S. epidermidis is to a large extent mediated by the methicillin resistance island-encoded peptide toxin, PSM-mec. PSM-mec contributed to bacterial survival in whole human blood and resistance to neutrophil-mediated killing, and caused significantly increased mortality and cytokine expression in a mouse sepsis model. Furthermore, we show that the PSM-mec peptide itself, rather than the regulatory RNA in which its gene is embedded, is responsible for the observed virulence phenotype. While toxins have never been clearly indicated in CNS infections, our study shows that an important type of infection caused by the predominant CNS species, S. epidermidis, is mediated to a large extent by a toxin. Of note, these findings suggest that CNS infections may be amenable to virulence-targeted drug development approaches.
We used microarrays to detail the global gene expression between S. epidermidis strain Rp62A and S. epidermidis strain Rp62A isogenic Δpsm-mec deletion mutants
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| Overall design |
We used microarrays to detail the global gene expression between five strains of Se.
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| Contributor(s) |
Qin L, Da F, Tan DC, Nguyen TH, Fu C, YTan V, McCausland JW, Sturdevant DE, Joo H, Queck SY, Cheung GY, Otto M |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Aug 05, 2016 |
| Last update date |
Jan 09, 2017 |
| Contact name |
Dan Sturdevant |
| E-mail(s) |
[email protected]
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| Phone |
4063639248
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| Organization name |
NIH
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| Department |
NIAID
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| Lab |
RTS
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| Street address |
903 S 4th street
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| City |
Hamilton |
| State/province |
MT |
| ZIP/Postal code |
59840 |
| Country |
USA |
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| Platforms (1) |
| GPL4692 |
[RMLchip3a520351] Affymetrix RML Custom Pathogenic chip 3 |
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| Samples (15)
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| GSM2263424 |
Staphylococcus epidermidis strain Rp62A rep 1 |
| GSM2263425 |
Staphylococcus epidermidis strain Rp62A rep 2 |
| GSM2263426 |
Staphylococcus epidermidis strain Rp62A rep 3 |
| GSM2263427 |
Staphylococcus epidermidis strain Rp62A isogenic Δpsm-mec deletion mutant rep 1 |
| GSM2263428 |
Staphylococcus epidermidis strain Rp62A isogenic Δpsm-mec deletion mutant rep 2 |
| GSM2263429 |
Staphylococcus epidermidis strain Rp62A isogenic Δpsm-mec deletion mutant rep 3 |
| GSM2265856 |
Staphylococcus epidermidis strain SE620 rep 1 |
| GSM2265857 |
Staphylococcus epidermidis strain SE620 rep 2 |
| GSM2265858 |
Staphylococcus epidermidis strain SE620 rep 3 |
| GSM2265859 |
Staphylococcus epidermidis strain SE620 Δmec mutant rep 1 |
| GSM2265860 |
Staphylococcus epidermidis strain SE620 Δmec mutant rep 2 |
| GSM2265861 |
Staphylococcus epidermidis strain SE620 Δmec mutant rep 3 |
| GSM2265862 |
Staphylococcus epidermidis strain SE620 Δpsm-mec mutant rep 1 |
| GSM2265863 |
Staphylococcus epidermidis strain SE620 Δpsm-mec mutant rep 2 |
| GSM2265864 |
Staphylococcus epidermidis strain SE620 Δpsm-mec mutant rep 3 |
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| Relations |
| BioProject |
PRJNA337973 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE85265_RAW.tar |
24.2 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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