What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2011 Aug 25
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

Items 1 - 3 of 3

1.	MBio. 2011 Sep 1;2(4). pii: e00175-11. doi: 10.1128/mBio.00175-11. Print 2011. Dot/Icm Type IVB Secretion System Requirements for Coxiella burnetii Growth in Human Macrophages. Beare PA, Gilk SD, Larson CL, Hill J, Stead CM, Omsland A, Cockrell DC, Howe D, Voth DE, Heinzen RA. Source Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA. Abstract ABSTRACT Central to Q fever pathogenesis is replication of the causative agent, Coxiella burnetii, within a phagolysosome-like parasitophorous vacuole (PV) in mononuclear phagocytes. C. burnetii modulates PV biogenesis and other host cell functions, such as apoptotic signaling, presumably via the activity of proteins delivered to the host cytosol by a Dot/Icm type IVB secretion system (T4BSS). In this study, we utilized a C. burnetii strain carrying IcmD inactivated by the Himar1 transposon to investigate the requirements for Dot/Icm function in C. burnetii parasitism of human THP-1 macrophage-like cells. The icmD::Tn mutant failed to secrete characterized T4BSS substrates, a defect that correlated with deficient replication, PV development, and apoptosis protection. Restoration of type IVB secretion and intracellular growth of the icmD::Tn mutant required complementation with icmD, -J, and -B, indicating a polar effect of the transposon insertion on downstream dot/icm genes. Induction of icmDJB expression at 1 day postinfection resulted in C. burnetii replication and PV generation. Collectively, these data prove that T4BSS function is required for productive infection of human macrophages by C. burnetii. However, illustrating the metabolic flexibility of C. burnetti, the icmD::Tn mutant could replicate intracellularly when sequestered in a PV generated by wild-type bacteria, where Dot/Icm function is provided in trans, and within a phenotypically similar PV generated by the protozoan parasite Leishmania amazonensis, where host cells are devoid of Dot/Icm T4BSS effector proteins. IMPORTANCECoxiella burnetii, the cause of human Q fever, is the only bacterial pathogen known to replicate in a vacuole resembling a phagolysosome. The organism manipulates host macrophages to promote the biogenesis of a vacuolar compartment permissive for growth. By analogy to the well-established cellular microbiology of Legionella pneumophila, the Dot/Icm type IVB secretion system of C. burnetii is implicated as a critical virulence factor in host cell modification that delivers proteins with effector functions directly into the host cell cytosol. Using new genetic tools, we verify that Dot/Icm function is essential for productive infection of human macrophages by C. burnetii. Interestingly, despite the production of homologous secretion systems, L. pneumophila and C. burnetii have strikingly different temporal requirements for Dot/Icm function during their respective infectious cycles.
	PMID: 21862628 [PubMed - in process]

2.	Future Microbiol. 2011 Aug;6:933-40. Antimicrobial effects of TiO(2) and Ag(2)O nanoparticles against drug-resistant bacteria and leishmania parasites. Allahverdiyev AM, Abamor ES, Bagirova M, Rafailovich M. Source Yildiz Technical University, Department of Bioengineering, Istanbul, Turkey. Abstract Nanotechnology is the creation of functional materials, devices and systems at atomic and molecular scales (1-100 nm), where properties differ significantly from those at a larger scale. The use of nanotechnology and nanomaterials in medical research is growing rapidly. Recently, nanotechnologic developments in microbiology have gained importance in the field of chemotherapy. Bacterial strains that are resistant to current antibiotics have become serious public health problems that raise the need to develop new bactericidal materials. Metal oxide nanoparticles, especially TiO(2) and Ag(2)O nanoparticles, have demonstrated significant antibacterial activity. Therefore, it is thought that this property of metal oxide nanoparticles could effectively be used as a novel solution strategy. In this review, we focus on the unique properties of nanoparticles, their mechanism of action as antibacterial agents and recent studies in which the effects of visible and UV-light induced TiO(2) and Ag(2)O nanoparticles on drug-resistant bacteria have been documented. In addition, from to previous results of our studies, antileishmanial effects of metal oxide nanoparticles are also demonstrated, indicating that metal oxide nanoparticles can also be effective against eukaryotic infectious agents. Conversely, despite their significant potential in antimicrobial applications, the toxicity of metal oxide nanoparticles restricts their use in humans. However, recent studies infer that metal oxide nanoparticles have considerable potential to be the first-choice for antibacterial and antiparasitic applications in the future, provided that researchers can bring new ideas in order to cope with their main problem of toxicity.
	PMID: 21861623 [PubMed - in process]

3.	Future Microbiol. 2011 Aug;6:847-50. Antiparasitic prodrug nifurtimox: revisiting its activation mechanism. Cerecetto H, González M. Source Grupo de Química Medicinal, Facultad de Química-Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay. Abstract Evaluation of: Hall BS, Bot C, Wilkinson SR. Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites. J. Biol. Chem. 286, 13088-13095 (2011). The prodrug nifurtimox has been one of the pharmacologic alternatives to treat Chagas disease and currently forms part of a combinational therapy to treat West African trypanosomiasis. Despite this, nifurtimox's mechanism of action is only partially understood and has been related to induction of oxidative stress in the target cell. An alternative mechanism involving reductive activation by a eukaryotic type I nitroreductase has been described. Bloodstream form Trypanosoma brucei overexpressing enzymes, proposed to metabolize nifurtimox, were generated and only cells with elevated levels of the nitroreductase displayed altered susceptibility to the drug, implying that it has a key role in drug action. Reduction of nifurtimox by trypanosomal type I nitroreductases was shown to be insensitive to oxygen and yielded a product characterized by liquid chromatography/mass spectrometry as an unsaturated open chain nitrile. This nitrile inhibited both parasite and mammalian cell growth at equivalent concentrations, in marked contrast to the parental prodrug. These studies indicated that nifurtimox selectivity against T. brucei could be the result of the expression of a parasite-encoded type I nitroreductase.
	PMID: 21861617 [PubMed - in process]