Phagocytosis by hemocytes, Drosophila macrophages, is essential for resistance to Streptococcus pneumoniae in adult flies. Activated macrophages require an increased supply of energy and we show here that a systemic metabolic switch, involving the release of glucose from glycogen, is required for effective resistance to S. pneumoniae. This metabolic switch is mediated by extracellular adenosine, as evidenced by the fact that blocking adenosine signaling in the adoR mutant suppresses the systemic metabolic switch and decreases resistance to infection, while enhancing adenosine effects by lowering adenosine deaminase ADGF-A increases resistance to S. pneumoniae. Further, that ADGF-A is later expressed by immune cells during infection to regulate these effects of adenosine on the systemic metabolism and immune response. Such regulation proved to be important during chronic infection caused by Listeria monocytogenes. Lowering ADGF-A specifically in immune cells prolonged the systemic metabolic effects, leading to lower glycogen stores, and increased the intracellular load of L. monocytogenes, possibly by feeding the bacteria. An adenosine-mediated systemic metabolic switch is thus essential for effective resistance but must be regulated by ADGF-A expression from immune cells to prevent the loss of energy reserves and possibly to avoid the exploitation of energy by the pathogen.
- MeSH
- adenosin farmakologie MeSH
- Drosophila melanogaster růst a vývoj imunologie metabolismus mikrobiologie MeSH
- energetický metabolismus MeSH
- extracelulární prostor metabolismus MeSH
- fagocytóza účinky léků imunologie MeSH
- hemocyty účinky léků imunologie metabolismus MeSH
- interakce hostitele a patogenu účinky léků MeSH
- Listeria monocytogenes účinky léků imunologie metabolismus MeSH
- listeriové infekce imunologie metabolismus mikrobiologie MeSH
- makrofágy účinky léků imunologie metabolismus MeSH
- mutace MeSH
- pneumokokové infekce imunologie metabolismus mikrobiologie MeSH
- proteiny Drosophily genetika metabolismus MeSH
- signální transdukce účinky léků imunologie MeSH
- Streptococcus pneumoniae účinky léků imunologie metabolismus MeSH
- vazodilatancia farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIMS: The aim of this study was to assess the potential risk posed to the human population by the presence of Listeria monocytogenes serotype 1/2c in food based on the characterization of virulence factors of Listeria involved in the invasion of host cells and sensitivity to antimicrobial agents. METHODS AND RESULTS: In addition to sequencing of the inlA and inlB genes, the presence of genes lapB, aut, fbpA, ami, vip and llsX was tested. A premature stop codon (PMSC) in the inlA gene was detected in all tested strains of serotype 1/2c and, concurrently, two novel PMSC mutation types were identified. However, neither PMSC in the inlB gene nor deletion of the lapB, aut, fbpA, ami and vip genes were found in any of the strains. The presence of the llsX gene was not confirmed. Even though all L. monocytogenes strains showed sensitivity to the tested antimicrobials on the basis of their phenotype, sequencing revealed the presence of IS1542 insertion in the inlA gene, indicating the possibility of sharing of mobile genetic elements associated with antimicrobial resistance among strains. CONCLUSIONS: Other than the presence of PMSCs in the inlA gene, no PMSC in inlB or deletion of other factors linked to the invasiveness of listeria were detected. Tested strains showed sensitivity to antibiotics used in the therapy of listeriosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Strains of L. monocytogenes serotype 1/2c typically carry a PMSC in the inlA gene, but these strains still represent a potential threat to public health. The possibility of transfer of IS1542, associated with resistance to vancomycin, between enterococci and Listeria spp. was revealed.
- MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální léková rezistence MeSH
- bakteriální proteiny genetika metabolismus MeSH
- faktory virulence genetika metabolismus MeSH
- fenotyp MeSH
- lidé MeSH
- Listeria monocytogenes účinky léků genetika izolace a purifikace metabolismus MeSH
- nesmyslný kodon MeSH
- potravinářská mikrobiologie * MeSH
- séroskupina MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The effect of recombinant divercin RV41 (DvnRV41) and its structural variants on the K-channel formation was determined. The growth of Listeria monocytogenes EGDe (sensitive phenotype) and its isogenic strain (resistant phenotype) was assessed in the presence of DvnRV41 combined or not with pinacidil, NS1619, cromakalim (as K-channel activators), iberiotoxin and glipizide (as K-channel blockers). The combined action of DvnRV41 and K activators permitted formation of ATP-dependent pores. The combination of DvnRV41 and ATP-dependent pore activator cromakalim inhibited the growth of sensitive strain. The antilisterial activity of structural variants was less important than that of DvnRV41 but their mode of action remained overall similar.
- MeSH
- adenosintrifosfát metabolismus MeSH
- antibakteriální látky metabolismus MeSH
- bakteriociny genetika metabolismus MeSH
- blokátory draslíkových kanálů metabolismus MeSH
- draslíkové kanály agonisté metabolismus MeSH
- Listeria monocytogenes účinky léků genetika růst a vývoj metabolismus MeSH
- mikrobiální testy citlivosti MeSH
- rekombinantní proteiny genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
