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Unique biofilm signature, drug susceptibility and decreased virulence in Drosophila through the Pseudomonas aeruginosa two-component system PprAB
- Source :
- PLoS Pathogens, PLoS Pathogens, Public Library of Science, 2012, 8 (11), pp.e1003052. ⟨10.1371/journal.ppat.1003052⟩, PLoS Pathogens, 2012, 8 (11), pp.e1003052. ⟨10.1371/journal.ppat.1003052⟩, PLoS Pathogens, Vol 8, Iss 11, p e1003052 (2012), PLoS Pathogens, Public Library of Science, 2012, pp.11:e1003052, PLoS Pathogens, Public Library of Science, 2012, Methods in Molecular Biology, 8 (11), pp.e1003052. ⟨10.1371/journal.ppat.1003052⟩
- Publication Year :
- 2012
- Publisher :
- HAL CCSD, 2012.
-
Abstract
- Bacterial biofilm is considered as a particular lifestyle helping cells to survive hostile environments triggered by a variety of signals sensed and integrated through adequate regulatory pathways. Pseudomonas aeruginosa, a Gram-negative bacterium causing severe infections in humans, forms biofilms and is a fantastic example for fine-tuning of the transition between planktonic and community lifestyles through two-component systems (TCS). Here we decipher the regulon of the P. aeruginosa response regulator PprB of the TCS PprAB. We identified genes under the control of this TCS and once this pathway is activated, analyzed and dissected at the molecular level the PprB-dependent phenotypes in various models. The TCS PprAB triggers a hyper-biofilm phenotype with a unique adhesive signature made of BapA adhesin, a Type 1 secretion system (T1SS) substrate, CupE CU fimbriae, Flp Type IVb pili and eDNA without EPS involvement. This unique signature is associated with drug hyper-susceptibility, decreased virulence in acutely infected flies and cytotoxicity toward various cell types linked to decreased Type III secretion (T3SS). Moreover, once the PprB pathway is activated, decreased virulence in orally infected flies associated with enhanced biofilm formation and dissemination defect from the intestinal lumen toward the hemolymph compartment is reported. PprB may thus represent a key bacterial adaptation checkpoint of multicellular and aggregative behavior triggering the production of a unique matrix associated with peculiar antibiotic susceptibility and attenuated virulence, a particular interesting breach for therapeutic intervention to consider in view of possible eradication of P. aeruginosa biofilm-associated infections.<br />Author Summary We unraveled that once the two-component system PprAB regulatory pathway is activated, Pseudomonas aeruginosa displays a unique hyper-biofilm phenotype due to a molecular signature combining a T1SS high molecular weight substrate, BapA, fimbriae of the chaperone-usher pathway, Type IVb pili and eDNA. Originally, this particular hyper-biofilm that is not strictly dependent on Psl or Pel exopolysaccharide (EPS) synthesis displays increased drug susceptibility, in contrary to previously reported biofilm lifestyle associated with increased resistance to antibiotics. PprB-dependent hyper-biofilm was also observed on intestinal mucosa of orally infected Drosophila flies in which it also displays a reduced capacity to cross the epithelial barrier from the intestinal lumen toward the hemolymph that consequently resulted in a reduced capacity to kill flies. Furthermore, constitutive activation of this PprB regulatory pathway triggers a reduced secretion of T3SS effectors which may account for the decreased virulence observed in epithelial and macrophage lineages and in acute Drosophila infections induced by septic injury. We appended in this study pieces of regulatory and molecular data that highlight the possibility to combat infections due to P. aeruginosa-biofilm with particular matrix.
- Subjects :
- MESH: Adhesins, Bacterial
Fimbria
Pathogenesis
medicine.disease_cause
MESH: Animals
Biology (General)
MESH: Bacterial Secretion Systems
Bacterial Secretion Systems
ComputingMilieux_MISCELLANEOUS
0303 health sciences
Genomics
3. Good health
Bacterial Pathogens
Host-Pathogen Interaction
Drosophila melanogaster
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Pseudomonas aeruginosa
MESH: Pseudomonas aeruginosa
Research Article
QH301-705.5
Immunology
Virulence
MESH: Biofilms
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
Microbiology
Bacterial genetics
Cell Line
MESH: Drosophila melanogaster
MESH: Fimbriae, Bacterial
03 medical and health sciences
Virology
medicine
Genetics
Animals
Secretion
Adhesins, Bacterial
Molecular Biology
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
030304 developmental biology
030306 microbiology
fungi
Biofilm
Bacteriology
RC581-607
MESH: Cell Line
Bacterial adhesin
Regulon
Biofilms
Fimbriae, Bacterial
Parasitology
Immunologic diseases. Allergy
Subjects
Details
- Language :
- English
- ISSN :
- 15537366 and 15537374
- Database :
- OpenAIRE
- Journal :
- PLoS Pathogens, PLoS Pathogens, Public Library of Science, 2012, 8 (11), pp.e1003052. ⟨10.1371/journal.ppat.1003052⟩, PLoS Pathogens, 2012, 8 (11), pp.e1003052. ⟨10.1371/journal.ppat.1003052⟩, PLoS Pathogens, Vol 8, Iss 11, p e1003052 (2012), PLoS Pathogens, Public Library of Science, 2012, pp.11:e1003052, PLoS Pathogens, Public Library of Science, 2012, Methods in Molecular Biology, 8 (11), pp.e1003052. ⟨10.1371/journal.ppat.1003052⟩
- Accession number :
- edsair.doi.dedup.....f65e697ee165211aea6d0f2096c3c9ff