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| Status |
Public on Sep 11, 2020 |
| Title |
An antibiofilm effect against Salmonella typhimurium rdar biofilm formation upon treatment with the macrolide clarithromycin |
| Organism |
Salmonella enterica subsp. enterica serovar Typhimurium |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Upon biofilm formation, production of extracellular matrix components and alteration in physiology and metabolism allows bacteria to build up multicellular communities which can facilitate nutrient acquisition during unfavorable conditions and provide protection towards various forms of environmental stresses to individual cells. Thus, bacterial cells become tolerant against antimicrobials and the immune system within biofilms. In the current study, we evaluated the antibiofilm activity of the macrolides clarithromycin and azithromycin. Clarithromycin showed antibiofilm activity against rdar (red, dry and rough) biofilm formation of the gastrointestinal pathogen Salmonella typhimurium ATCC14028 Nalr at 1.56 µM subinhibitory concentration in standing culture and dissolved cell aggregates at 15 µM in a microaerophilic environment suggesting that the oxygen level affects the activity of the drug. Treatment with clarithromycin significantly decreased transcription and production of the rdar biofilm activator CsgD, with biofilm genes such as csgB and adrA to be consistently downregulated. While fliA and other flagellar regulon genes were upregulated, apparent motility was downregulated. RNA sequencing showed a holistic cell response upon clarithromycin exposure, whereby not only genes involved in the biofilm-related regulatory pathways, but also genes that likely contribute to intrinsic antimicrobial resistance, and the heat shock stress response were differentially regulated. Most significantly, clarithromycin exposure shifts the cells towards an apparent oxygen- and energy- depleted status, whereby the metabolism that channels into oxidative phosphorylation is downregulated, and energy gain by degradation of propane 1,2-diol, ethanolamine and L-arginine catabolism, potentially also to prevent cytosolic, is upregulated. This analysis will allow the subsequent identification of novel intrinsic antimicrobial resistance determinants.
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| Overall design |
RNA isolation from six samples; three samples untreated without clarithromycin, three samples treated with 15 µM clarithromycin. All samples contained 1.5 (v/v) % DMSO.
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| Contributor(s) |
Zafar M, Choudhary HJ, Shafeeq S, Römling U |
| Citation missing |
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| |
| Submission date |
Sep 09, 2020 |
| Last update date |
Sep 11, 2020 |
| Contact name |
Ute Römling |
| E-mail(s) |
ute.romling@ki.se
|
| Organization name |
Karolinska Institutet
|
| Department |
Department of Microbiology, Tumor and Cell Biology
|
| Street address |
Solnavägen 9
|
| City |
Stockholm |
| ZIP/Postal code |
17177 |
| Country |
Sweden |
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| Platforms (1) |
| GPL28222 |
NextSeq 550 (Salmonella enterica subsp. enterica serovar Typhimurium) |
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| Samples (6)
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| GSM4773468 |
Cell aggregates of S. Typhimurium UMR1 [1_S1] |
| GSM4773469 |
Cell aggregates of S. Typhimurium UMR1 [2_S2] |
| GSM4773470 |
Cell aggregates of S. Typhimurium UMR1 [3_S3] |
| GSM4773471 |
Cell aggregates of S. Typhimurium UMR1 treated with 15 µM clarithromycin [4_S4] |
| GSM4773472 |
Cell aggregates of S. Typhimurium UMR1 treated with 15 µM clarithromycin [5_S5] |
| GSM4773473 |
Cell aggregates of S. Typhimurium UMR1 treated with 15 µM clarithromycin [6_S6] |
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| Relations |
| BioProject |
PRJNA662483 |
| SRA |
SRP281819 |
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