Effect of monensin on the invasiveness and multiplication of Legionella pneumophila

Goldoni, Paola; Pastoris, Maddalena Castellani; Cattani, L.; Peluso, Carmela; Sinibaldi, L.; Orsi, N

doi:10.1099/00222615-42-4-269

Cited by 12 publications

(14 citation statements)

References 36 publications

(2 reference statements)

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“…Reagents that neutralize the endosomal compartment reportedly prevent L . pneumophila replication in macrophages, HeLa cells, or amebae 32374546. Finally, C. burnettii , an obligate intracellular pathogen closely related to L .…”

Section: Discussionmentioning

confidence: 99%

Legionella pneumophila Replication Vacuoles Mature into Acidic, Endocytic Organelles

Sturgill-Koszycki

Swanson

2000

The Journal of Experimental Medicine

214

239

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After ingestion by macrophages, Legionella pneumophila inhibits acidification and maturation of its phagosome. After a 6–10-h lag period, the bacteria replicate for 10–14 h until macrophage lysis releases dozens of progeny. To examine whether the growth phase of intracellular L. pneumophila determines the fate of its phagosome, interactions between the endosomal network and pathogen vacuoles were analyzed throughout the primary infection period. Surprisingly, as L. pneumophila replicated exponentially, a significant proportion of the vacuoles acquired lysosomal characteristics. By 18 h, 70% contained lysosomal-associated membrane protein 1 (LAMP-1) and 40% contained cathepsin D; 50% of the vacuoles could be labeled by endocytosis, and the pH of this population of vacuoles averaged 5.6. Moreover, L. pneumophila appeared to survive and replicate within lysosomal compartments: vacuoles harboring more than five bacteria also contained LAMP-1, inhibition of vacuole acidification and maturation by bafilomycin A1 inhibited bacterial replication, bacteria within endosomal vacuoles responded to a metabolic inducer by expressing a gfp reporter gene, and replicating bacteria obtained from macrophages, but not broth, were acid resistant. Understanding how L. pneumophila first evades and then exploits the endosomal pathway to replicate within macrophages may reveal the mechanisms governing phagosome maturation, a process also manipulated by Mycobacteria, Leishmania, and Coxiella.

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Section: Discussionmentioning

confidence: 99%

Legionella pneumophila Replication Vacuoles Mature into Acidic, Endocytic Organelles

Sturgill-Koszycki

Swanson

2000

The Journal of Experimental Medicine

214

239

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“…Ingestion assay of legionellas by HeLa cells. Ingestion assay and bacterial counts were carried out as previously described (14), except for the bacterial concentration of the inoculum which was 4X 104 cfu/ml. Effect of drugs on the internalisation and intracellular multiplication of Legionella.…”

Section: Methodsmentioning

confidence: 99%

“…Ingestion assay and bacterial counts were carried out as previously described (14), except for the bacterial concentration of the inoculum which was 4X 104 cfu/ml.…”

Section: Methodsmentioning

confidence: 99%

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Multiplication of Legionella pneumophila in HeLa Cells in the Presence of Cytoskeleton and Metabolic Inhibitors

Goldoni

Cattani

Carrara

et al. 1998

Microbiology and Immunology

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A study has been carried out on the action of cytoskeleton and metabolic inhibitors on intracellular multiplication in HeLa cells of a virulent strain of Legionella pneumophila serogroup 6. The effects of the substances were separately tested on both penetration and intracellular multiplication of L. pneumophila. Only cytochalasin A and 2-deoxy-D-glucose (2dG) affected bacterial internalisation, whereas intracellular multiplication was inhibited by cytochalasins A, B, C, D and J (D being the most active) and by 2dG with a dose-response effect. The action of 2dG was counteracted by 50 mm glucose. Experiments carried out with cytochalasin D and a rhodamine-phalloidin conjugate showed the involvement of cytoskeletal elements in intracellular multiplication of Legionella; compounds acting on microtubules had no effect.

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“…Moreover, monensin exhibits bacteriostatic activity against a clinical isolate of Legionella pneumophila in vitro [58] Monensin inhibits the mycobacterium avium subspecies paratuberculosis in radiometric culture [59]. Notably, monensin has potent in vitro and in vivo antimalarial activity [60,61].…”

Section: Discussionmentioning

confidence: 99%

Monensin Induced Suicidal Erythrocyte Death

Bhavsar

Eberhard

Bobbala

et al. 2010

Cell Physiol Biochem

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Eryptosis, the suicidal erythrocyte death, is characterized by cell membrane scrambling and cell shrinkage. Eryptosis may be triggered by excessive hyperosmotic or isosmotic cell shrinkage leading to increase of cytosolic Ca²⁺ concentration. Eryptosis is further stimulated by the K⁺ ionophore valinomycin, which leads to exit of KCl and osmotically obliged water, or by energy (glucose) depletion, which compromises the function of the Na⁺/K⁺ ATPase thus increasing cytosolic Na⁺ concentration. The present study explored whether the Na⁺ ionophore monensin affects erythrocyte cell volume and eryptosis. The cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, cell volume from forward scatter in FACS analysis, cytosolic Ca²⁺ concentration from Fluo3 fluorescence and the cytosolic ATP concentration from a luciferase-based assay. Within 24 hours, exposure to monensin (0.1-10 µg/ml) significantly increased forward scatter, cytosolic Ca²⁺ concentration and annexin V-binding. Glucose depletion was followed by decreased forward scatter and increased cytosolic Ca²⁺ concentration and annexin V-binding. The effect on forward scatter was partially reversed, the effect on cytosolic Ca²⁺ concentration and annexin V binding augmented by additional treatment with monensin. In conclusion, monensin dissociates the alterations of cell membrane and cell volume in suicidal erythrocyte death.

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Effect of monensin on the invasiveness and multiplication of Legionella pneumophila

Cited by 12 publications

References 36 publications

Legionella pneumophila Replication Vacuoles Mature into Acidic, Endocytic Organelles

Legionella pneumophila Replication Vacuoles Mature into Acidic, Endocytic Organelles

Multiplication of Legionella pneumophila in HeLa Cells in the Presence of Cytoskeleton and Metabolic Inhibitors

Monensin Induced Suicidal Erythrocyte Death

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