Showing papers in "Apmis in 2009"

Communication between Toxoplasma gondii and its host: impact on parasite growth, development, immune evasion, and virulence

Abstract: Toxoplasma gondii is an obligate intracellular protozoan parasite that can infect most warm-blooded animals and cause severe and life-threatening disease in developing fetuses and in immune-compromised patients. Although Toxoplasma was discovered over 100 years ago, we are only now beginning to appreciate the importance of the role that parasite modulation of its host has on parasite growth, bradyzoite development, immune evasion, and virulence. The goal of this review is to highlight these findings, to develop an integrated model for communication between Toxoplasma and its host, and to discuss new questions that arise out of these studies.

Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disabling the protection against polymorphonuclear leukocytes

Abstract: Channing Laboratory, Department of Medicine,Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USAvan Gennip M, Christensen LD, Alhede M, Phipps R, Jensen PO, Christophersen L, Pamp SJ, MoserC, Mikkelsen PJ, Koh AY, Tolker-Nielsen T, Pier GB, H iby N, Givskov M, Bjarnsholt T.Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disablingthe protection against polymorphonuclear leukocytes. APMIS 2009; 117: 537–46.Manyofthevirulencefactorsproducedbytheopportunistic humanpathogenPseudomonasaeruginosaare quorum-sensing (QS) regulated. Among these are rhamnolipids, which have been shown to causelysis of several cellular components of the human immune system, e.g. monocyte-derived macrophagesand polymorphonuclear leukocytes (PMNs). We have previously shown that rhamnolipids producedby P. aeruginosa cause necrotic death of PMNs in vitro. This raises the possibility that rhamnolipidsmay function as a ‘biofilm shield’ in vivo, which contributes significantly to the increased tolerance ofP.aeruginosabiofilmstoPMNs.Inthepresentstudy,wedemonstratetheimportanceoftheproductionof rhamnolipids in the establishment and persistence of P. aeruginosa infections, using an in vitro bio-film system, an intraperitoneal foreign-body model and a pulmonary model of P. aeruginosa infectionsin mice. Our experimental data showed that a P. aeruginosa strain, unable to produce any detectablerhamnolipids due to an inactivating mutation in the single QS-controlled rhlA gene, did not inducenecrosis of PMNs in vitro and exhibited increased clearance compared with its wild-type counterpartin vivo. Conclusively, the results support our model that rhamnolipids are key protective agents ofP. aeruginosa against PMNs.Key words: Rhamnolipid; Pseudomonas aeruginosa; mouse models; biofilm; PMN.