[leish-l] Fwd: Articles found by RefScout -2005/10/26 - 2005/43
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Thu Oct 27 10:29:49 BRST 2005
Date: Wed, 26 Oct 2005 05:36:21
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This is RefScout-Newsletter 43/2005.
REQUEST: [ leishmaniasis ]
(17 articles match this request)
PMID: 16150644
TITLE: Chemotherapy of trypanosomiases and leishmaniasis.
AUTHORS: Simon L Croft, Michael P Barrett, Julio A Urbina
AFFILIATION: Drugs for Neglected Diseases Initiative, 1 Place Saint-Gervais,
CH-1201 Geneva, Switzerland.
REFERENCE: Trends Parasitol 2005 Nov 21(11):508-12
New formulations, therapeutic switching of the established drugs
amphotericin B and paromomycin, and the serendipitous discovery of
miltefosine have markedly improved leishmaniasis chemotherapy in the
past 21 years. The situation for the two trypanosomiases has been less
encouraging. Apart from the introduction of eflornithine for the
treatment of late-stage human African trypanosomiasis, with its serious
limitations in terms of cost and difficulty of administration, no new
drugs have been incorporated into the chemotherapeutic arsenal in the
past 25 years, despite important advances in knowledge of the biology of
the etiological agents and the pathophysiology of these diseases. In
the case of Chagas disease, several classes of compound that target the
validated biochemical pathways of the parasite (e.g. inhibitors of
sterol biosynthesis and cysteine proteases) are in the pipeline. With
the availability of complete genome sequences for all three pathogens,
and methods for rapid validation of targets, it is hoped that much-
needed amelioration will occur soon. Financial constraints continue to
represent a major hurdle to drug development. However, the appearance of
not-for-profit product-development partnerships offers a new paradigm
for bringing new drugs to patients.
PMID: 16239566
TITLE: Interleukin-4 (IL-4) and IL-10 Collude in Vaccine Failure for Novel
Exacerbatory Antigens in Murine Leishmania major Infection.
AUTHORS: Mark T M Roberts, Carmel B Stober, Andrew N McKenzie, Jenefer M
Blackwell
AFFILIATION: Cambridge Institute for Medical Research, Wellcome Trust/MRC
Building, Addenbrooke's Hospital, Hills Rd., Cambridge CB2 2XY, United Kingdom.
jennie.blackwell at cimr.cam.ac.uk.
REFERENCE: Infect Immun 2005 Nov 73(11):7620-8
Leishmaniasis affects 12 million people but there are no vaccines in
routine use. Recently, we used DNA vaccination in a susceptible BALB/c
high-dose model of infection to screen 100 novel Leishmania major genes
as vaccine candidates. In addition to finding novel protective antigens
, we identified several antigens that reproducibly exacerbated disease.
Here we examined the immune response to two of these antigens, lmd29 and
584C, that were originally identified in an expressed sequence tag cDNA
sequencing project. We show that, in addition to exacerbating disease
in susceptible BALB/c mice, these antigens retain a propensity to
exacerbate disease in resistant C57BL/6 mice. This ability to exacerbate
disease was lost when susceptible BALB/c mice were rendered resistant
by disruption of the genes encoding interleukin-4 (IL-4) alone, IL-4/IL-
13, or IL-4, IL-5, IL-9, and IL-13. Failure to exacerbate disease was
associated with reduced IL-5 and IL-10 production in IL-4 knockout mice
. Treatment of lmd29-vaccinated mice with anti-IL-10 receptor antibody
prior to challenge infection converted exacerbation in wild-type BALB/c
mice into highly significant antigen-specific protection. These studies
demonstrate that some highly immunogenic antigens of L. major, while
having an intrinsic capacity to exacerbate disease in the context of
otherwise T helper 1-promoting DNA vaccine delivery, can be rendered
protective by the removal of functional IL-10.
PMID: 16235183
TITLE: Tegumentary leishmaniasis as a manifestation of immune reconstitution
inflammatory syndrome in 2 patients with AIDS.
AUTHORS: Maria P Posada-Vergara, Jose A L Lindoso, Jose Eduardo Tolezano, Vera
Lucia Pereira-Chioccola, Marcos Vinicius Silva, Hiro Goto
AFFILIATION: Laboratorio de Soroepidemiologia e Imunobiologia, Instituto de
Medicina Tropical de Sao Paulo, Departamento de Doencas Infecciosas e
Parasitarias and Instituto de Infectologia Emilio Ribas, Sao Paulo, Brazil.
REFERENCE: J Infect Dis 2005 Nov 192(10):1819-22
Immune reconstitution inflammatory syndromes (IRISs) have been reported
in patients with human immunodeficiency virus/acquired immunodeficiency
syndrome (AIDS) since the introduction of highly active antiretroviral
therapy (HAART). This syndrome is characterized by clinical
manifestations of opportunistic infections when signs of immune
reconstitution are observed during therapy. We report on leishmaniasis,
suggestive of HAART-induced IRIS, in 2 patients with AIDS. After
beginning HAART, 1 patient presented with disseminated, tegumentary
lesions, whereas the other patient's preexisting lesions worsened and
became more extensive; however, at the same time, their CD4(+) T cell
counts were recovering and their virus loads were decreasing
significantly. The lesions healed with anti-Leishmania therapy.
PMID: 16243129
TITLE: Leishmania tropica in northern Israel: a clinical overview of an emerging
focus.
AUTHORS: Ayelet Shani-Adir, Stephanie Kamil, Dganit Rozenman, Eli Schwartz,
Michal Ramon, Lucia Zalman, Abed Nasereddin, Charles L Jaffe, Moshe Ephros
AFFILIATION: Department of Dermatology, Emek Medical Center, Afula, Israel.
adir-sh at zahav.net.il
REFERENCE: J Am Acad Dermatol 2005 Nov 53(5):810-5
BACKGROUND: In Israel, most cutaneous leishmaniasis (CL) is caused by
Leishmania major. Recently a new focus of CL caused by Leishmania
tropica has been described in Tiberias and the surrounding area of
northern Israel. OBJECTIVE: The aim of this study was to evaluate
clinical (size, number, location, and type of lesion) and laboratory (
culture and polymerase chain reaction [PCR] analysis) parameters at
diagnosis, response to treatment, and outcome of patients with CL due to
L tropica. METHODS: Between September 2002 and March 2004, patients
with direct smear-confirmed CL were evaluated; clinical records were
reviewed and a telephone survey was performed. RESULTS: Forty nine
patients, 34 (69%) male and 15 (31%) female, were studied. Mean age was
31.1 years (median 26 years, range 1-70); 76% of patients live in
Tiberias and the surrounding area. The mean number of lesions was 2.6 (
median 2, range 1-10). Lesions were commonly located on the face (61%)
and upper limbs (57%). PCR analysis was performed in 27 patients and was
positive for L tropica in 26. Fifty percent of patients studied
received multiple therapeutic regimens because of incomplete response or
treatment failure. Topical paromomycin was used in 44 patients (90%),
with a complete response reported in only 17 (39%); of the 9 patients
treated with intralesional sodium stibogluconate, a complete response
was reported in 6 (67%); of the 5 patients treated with intravenous
sodium stibogluconate, 4 (80%) were cured. LIMITATIONS: The relatively
small number of patients studied combined with the fact that some were
assessed retrospectively limit our conclusions. In addition, 50% of the
patients studied received multiple therapeutic regimens because of
failure of, or incomplete responses to, their initial therapy, thereby
making comparisons difficult. CONCLUSIONS: The cure rate in those
completing a course of antimony therapy, either 10 or more days of
intravenous therapy or therapy administered intralesionally, was 75% (95
% confidence interval [CI], 50.5-99.5%) as compared with 45% (95% CI, 28
.9-60.5%) among those completing at least 10 days of topical paromomycin
. To date, no standardized, simple, safe, and highly effective regimen
for treating L tropica exists. Large, controlled clinical trials to
evaluate current treatment regimens as well as new medications for CL,
and especially CL attributed to L tropica, are urgently needed.
PMID: 16211660
TITLE: Effect of Pyrazoloquinoline Derivatives on the Growth of Leishmania
donovani Promastigotes.
AUTHORS: Ahmed Al-Qahtani, Yunus M Siddiqui, Adnan A Bekhit, Ola A El-Sayed,
Hassan Y Aboul-Enein, Mohammed N Al-Ahdalb
AFFILIATION: Zoology Department, College of Science, King Saud University,
Riyadh, Saudi Arabia.
REFERENCE: Arch Pharm (Weinheim) 2005 Oct 338(10):484-7
A screening study was conducted to examine the effect of a series of
synthesized pyrazoloquinoline derivatives on the growth of Leishmania
donovani promastigotes. Sixteen compounds were tested, ten of which
showed an inhibitory effect on the growth of promastigotes. Compound 1
demonstrated potent antileishmanial activity, followed by compounds 3
and 7. Some compounds showed less significant activities, while others
exhibited little or no activity. Some of these compounds may be
potential candidates for future treatment of leishmaniasis.
PMID: 16244972
TITLE: Pancreatitis associated with N-methyl-glucamine therapy in a dog with
leishmaniasis.
AUTHORS: G Aste, M Di Tommaso, J M Steiner, D A Williams, A Boari
AFFILIATION: Department of Veterinary Clinical Sciences, Section of Internal
Medicine, Faculty of Veterinary Medicine, University of Teramo, 64100, Teramo,
Italy, gaste at unite.it.
REFERENCE: Vet Res Commun 2005 Aug 29 Suppl 2():269-72
PMID: 16244980
TITLE: Real-time PCR in dogs treated for leishmaniasis with allopurinol.
AUTHORS: M G Pennisi, S Reale, S Lo Giudice, M Masucci, S Caracappa, M Vitale, F
Vitale
AFFILIATION: Department of Veterinary Medical Science, Faculty of Veterinary
Medicine, University of Messina, Polo Universitario dell'Annunziata, 98168,
Messina, Italy, MariaGrazia.Pennisi at unime.it.
REFERENCE: Vet Res Commun 2005 Aug 29 Suppl 2():301-3
PMID: 16244984
TITLE: Feline leishmaniasis and ehrlichiosis: serological investigation in
abruzzo region.
AUTHORS: S Vita, D Santori, I Aguzzi, E Petrotta, A Luciani
AFFILIATION: Dipartimento di Scienze Cliniche Veterinarie, Università degli
Studi di Teramo, Viale Crispi 212, I-64100, Teramo, Italy, boari at unite.it.
REFERENCE: Vet Res Commun 2005 Aug 29 Suppl 2():319-21
PMID: 16122087
TITLE: Vaccinations with live-attenuated Leishmania major promastigotes and
challenge infection with L. major in BALB/c mice.
AUTHORS: J A Onyalo, D M Mwala, C O Anjili, A S Orago, W K Tonui
AFFILIATION: Zoology Department, Kenyatta University, P.O. box 43844, Nairobi,
Kenya.
REFERENCE: East Afr Med J 2005 Apr 82(4):193-7
BACKGROUND: Currently there is no vaccine available in use against any
form of leishmaniases worldwide. OBJECTIVE: To assess potential of a
live-attenuated Leishmania major promastigates, for protection against a
challenge infection with L. major in BALB/c mice. DESIGN: A laboratory
based study. SETTING: Study was carried out at Centre for Biotechnology
Research and Development, Kenya Medical Research Institute, Nairobi.
RESULTS: The greatest protection against challenge with L. major was
seen in mice immunised with live parasites (P < 0.001) compared to
vaccinations with heat killed or soluble antigens. In general, immunised
mice produced high level of antileishmanial antibodies and T cell
stimulation to their respective antigens. CONCLUSIONS: Our live-
attenuated parasites produced by serial sub-culture of L. major
parasites 118 times showed the capacity to induce appropriate cell-
mediated immune responses and protection against L. major infection in
BALB/c mice. Data also suggests that these parasites do not revert to
virulence when injected subcutaneously in mice.
********************************************************************************************************************
The following references are revised files and are brought to you in accordance
to license agreement with the NLM.
********************************************************************************************************************
PMID: 12117930
TITLE: Immunization with a polyprotein vaccine consisting of the T-Cell antigens
thiol-specific antioxidant, Leishmania major stress-inducible protein 1, and
Leishmania elongation initiation factor protects against leishmaniasis.
AUTHORS: Rhea N Coler, Yasir A W Skeiky, Karen Bernards, Kay Greeson, Darrick
Carter, Charisa D Cornellison, Farrokh Modabber, Antonio Campos-Neto, Steven G
Reed
AFFILIATION: Infectious Disease Research Institute, Seattle, Washington 98104,
USA. coler at idri.org
REFERENCE: Infect Immun 2002 Aug 70(8):4215-25
Development of an effective vaccine against Leishmania infection is a
priority of tropical disease research. We have recently demonstrated
protection against Leishmania major in the murine and nonhuman primate
models with individual or combinations of purified leishmanial
recombinant antigens delivered as plasmid DNA constructs or formulated
with recombinant interleukin-12 (IL-12) as adjuvant. In the present
study, we immunized BALB/c mice with a recombinant polyprotein
comprising a tandem fusion of the leishmanial antigens thiol-specific
antioxidant, L. major stress-inducible protein 1 (LmSTI1), and
Leishmania elongation initiation factor (LeIF) delivered with adjuvants
suitable for human use. Aspects of the safety, immunogenicity, and
vaccine efficacy of formulations with each individual component, as well
as the polyprotein referred to as Leish-111f, were assessed by using
the L. major challenge model with BALB/c mice. No adverse reactions were
observed when three subcutaneous injections of the Leish-111f
polyprotein formulated with either MPL-squalene (SE) or Ribi 529-SE were
given to BALB/c mice. A predominant Th1 immune response characterized
by in vitro lymphocyte proliferation, gamma interferon production, and
immunoglobulin G2A antibodies was observed with little, if any, IL-4.
Moreover, Leish-111f formulated with MPL-SE conferred immunity to
leishmaniasis for at least 3 months. These data demonstrate success at
designing and developing a prophylactic leishmaniasis vaccine that
proved effective in a preclinical model using multiple leishmanial
antigens produced as a single protein delivered with a powerful Th1
adjuvant suitable for human use.
PMID: 12010969
TITLE: Vaccination with plasmid DNA encoding TSA/LmSTI1 leishmanial fusion
proteins confers protection against Leishmania major infection in susceptible
BALB/c mice.
AUTHORS: A Campos-Neto, J R Webb, K Greeson, R N Coler, Y A W Skeiky, S G Reed
AFFILIATION: Infectious Disease Research Institute. Corixa Corporation, Seattle,
Washington 98104, USA. acampos at idri.org
REFERENCE: Infect Immun 2002 Jun 70(6):2828-36
We have recently shown that a cocktail containing two leishmanial
recombinant antigens (LmSTI1 and TSA) and interleukin-12 (IL-12) as an
adjuvant induces solid protection in both a murine and a nonhuman
primate model of cutaneous leishmaniasis. However, because IL-12 is
difficult to prepare, is expensive, and does not have the stability
required for a vaccine product, we have investigated the possibility of
using DNA as an alternative means of inducing protective immunity. Here
, we present evidence that the antigens TSA and LmSTI1 delivered in a
plasmid DNA format either as single genes or in a tandem digene
construct induce equally solid protection against Leishmania major
infection in susceptible BALB/c mice. Immunization of mice with either
TSA DNA or LmSTI1 DNA induced specific CD4(+)-T-cell responses of the
Th1 phenotype without a requirement for specific adjuvant. CD8 responses
, as measured by cytotoxic-T-lymphocyte activity, were generated after
immunization with TSA DNA but not LmSTI1 DNA. Interestingly, vaccination
of mice with TSA DNA consistently induced protection to a much greater
extent than LmSTI1 DNA, thus supporting the notion that CD8 responses
might be an important accessory arm of the immune response for acquired
resistance against leishmaniasis. Moreover, the protection induced by
DNA immunization was specific for infection with Leishmania, i.e., the
immunization had no effect on the course of infection of the mice
challenged with an unrelated intracellular pathogen such as
Mycobacterium tuberculosis. Conversely, immunization of BALB/c mice with
a plasmid DNA that is protective against challenge with M. tuberculosis
had no effect on the course of infection of these mice with L. major.
Together, these results indicate that the protection observed with the
leishmanial DNA is mediated by acquired specific immune response rather
than by the activation of nonspecific innate immune mechanisms. In
addition, a plasmid DNA containing a fusion construct of the two genes
was also tested. Similarly to the plasmids encoding individual proteins
, the fusion construct induced both specific immune responses to the
individual antigens and protection against challenge with L. major.
These results confirm previous observations about the possibility of DNA
immunization against leishmaniasis and lend support to the idea of
using a single polygenic plasmid DNA construct to achieve polyspecific
immune responses to several distinct parasite antigens.
PMID: 11349082
TITLE: Protection against cutaneous leishmaniasis induced by recombinant
antigens in murine and nonhuman primate models of the human disease.
AUTHORS: A Campos-Neto, R Porrozzi, K Greeson, R N Coler, J R Webb, Y A Seiky, S
G Reed, G Grimaldi
AFFILIATION: Infectious Disease Research Institute, Seattle, Washington 98104,
USA. acampos at idri.org
REFERENCE: Infect Immun 2001 Jun 69(6):4103-8
Leishmaniasis affects approximately 2 million people each year
throughout the world. This high incidence is due in part to the lack of
an efficacious vaccine. We present evidence that the recombinant
leishmanial antigens LmSTI1 and TSA, which we identified and
characterized previously, induce excellent protection in both murine and
nonhuman primate (rhesus monkey) models of human cutaneous
leishmaniasis. The remarkable protection induced by LmSTI1 and TSA in an
animal model that is evolutionarily close to humans qualifies this
antigen combination as a promising candidate subunit vaccine against
human leishmaniasis.
PMID: 13881433
TITLE: [Italian foci of kala-azar and the problem of leishmaniasis in Southern
Europe.]
AUTHORS: A CORRADETTI
REFERENCE: Rend Ist Sup Sanit 1961 24():281-4
PMID: 13420605
TITLE: [Epidemiological studies of kala azar in the Promontorio Garganico
(Puglie, Province of Foggia).]
AUTHORS: A CORRADETTI, G SACCA, I NERI
REFERENCE: Rend Ist Sup Sanit 1956 19(12):1230-6
PMID: 13255107
TITLE: [A focus of kala-azar in Monte Argentario, Tuscan Tyrrhenian coast.]
AUTHORS: A CORRADETTI, I NERI
REFERENCE: Rend Ist Sup Sanit 1955 18(5):376-9
PMID: 13186193
TITLE: [The fight against leishmaniasis by means of the Phlebotomus control in
Italy.]
AUTHORS: A CORRADETTI
REFERENCE: Rend Ist Sup Sanit 1954 17(5):374-84
PMID: 14958069
TITLE: [Epidemiological studies on cutaneous leishmaniasis in Abruzzo and
experience with total interruption of transmission (1948-50).]
AUTHORS: A CORRADETTI
REFERENCE: Rend Ist Sup Sanit 1952 15(3):181-7
REQUEST: [ leishmania ]
(18 articles match this request. 7 articles matching other requests removed)
PMID: 16239557
TITLE: Invariant NKT Cells Are Essential for the Regulation of Hepatic CXCL10
Gene Expression during Leishmania donovani Infection.
AUTHORS: Mattias Svensson, Soombul Zubairi, Asher Maroof, Fatima Kazi, Masaru
Taniguchi, Paul M Kaye
AFFILIATION: Immunology and Infection Unit, Department of Biology, University of
York, Heslington, York YO10 5YW, United Kingdom. pmk2 at york.ac.uk.
REFERENCE: Infect Immun 2005 Nov 73(11):7541-7
Gamma interferon (IFN-gamma)-regulated chemokines of the CXC family have
been implicated as key regulators of a variety of T-cell-dependent
inflammatory processes. However, the cellular source(s) of IFN-gamma
that regulates their early expression has rarely been defined. Here, we
have directly addressed this question in mice after Leishmania donovani
infection. Comparison of CXCL10 mRNA accumulation in normal and IFN-
gamma-deficient mice confirmed an absolute requirement for IFN-gamma for
sustained (24 h) expression of CXCL10 mRNA accumulation in this model.
In normal mice, IFN-gamma was produced by both CD3(int) NK1.1(+) NKT
cells and CD3(-) NK1.1(+) NK cells, as detected by intracellular flow
cytometry. Strikingly, B6.Jalpha281(-/-) mice lacking NKT cells that
express the invariant Valpha14Jalpha18 T-cell-receptor alpha chain,
although retaining a significant population of IFN-gamma-producing NK
cells and NKT cells, were unable to sustain CXCL10 mRNA accumulation.
These data indicate that invariant NKT cells are indispensable for the
regulation of hepatic CXCL10 gene expression during L. donovani
infection.
PMID: 16237047
TITLE: Cutting edge: a critical role for gene silencing in preventing excessive
type 1 immunity.
AUTHORS: Anne S Hutchins, David Artis, Brian D Hendrich, Adrian P Bird, Phillip
Scott, Steven L Reiner
AFFILIATION: Abramson Family Cancer Research Institute and Department of
Medicine and.
REFERENCE: J Immunol 2005 Nov 175(9):5606-10
Immunity often depends on proper cell fate choice by helper T
lymphocytes. A naive cell, with minimal expression of IFN-gamma and IL-4
, must give rise to progeny expressing high levels of either one, but
not both, of those cytokines to defend against protozoan and helminthic
pathogens, respectively. In the present study, we show that inactivation
of the Mbd2 gene, which links DNA methylation and repressed chromatin,
results in enhanced resistance to the protozoan parasite Leishmania
major but impaired immunity to the intestinal helminth Trichuris muris.
Helper T cells from methyl CpG-binding domain protein-2-deficient mice
exhibit exuberant patterns of cytokine expression despite appropriate
silencing of genes encoding the lineage-specifying factors T-bet and
GATA-3. These results suggest that gene silencing can facilitate the
ability of a progenitor cell to give rise to appropriately
differentiated daughter cells in vivo. These findings also point to
novel pathways that could participate in genetic control of resistance
to infection and autoimmunity.
PMID: 16046090
TITLE: In vitro cytotoxic, antileishmanial and antifungal activities of
ethnopharmacologically selected Gabonese plants.
AUTHORS: M Lamidi, C Digiorgio, F Delmas, A Favel, C Eyele Mve-Mba, M L Rondi, E
Ollivier, L Nze-Ekekang, G Balansard
AFFILIATION: IPHAMETRA (Institute of Traditional Pharmacopoeia and Medicine),
CENAREST, BP 842 Libreville, Gabon.
REFERENCE: J Ethnopharmacol 2005 Nov 102(2):185-90
Seventy-seven crude extracts from leaves and stem barks of 15 Gabonese
plants used in traditional medicine were evaluated for their cytotoxic,
antileishmanial and antifungal activities. Most of the extracts
exhibited cytotoxic activities toward human monocytes, and most
particularly the hydromethanolic 50% (v/v) fraction of Ganophyllum
giganteum leaves (IC(50)=1.3mug/ml) as well as the methanolic extracts
of Polyalthia suaveolens, Dioscorea preussii, Augouardia letestui leaves
and Cola lizae stem barks (IC(50)<5mug/ml). The methanolic extract
of Polyalthia suaveolens displayed a strong antiproliferative activity
against the promastigote form of Leishmania infantum parasites and
presented a good antifungal activity on all the tested strains (IC(50)&
lt;1mg/ml). This extract was divided into six fractions: fraction F6
demonstrated a cytotoxic activity stronger than those of the crude
extract (IC(50)=0.6mug/ml), fractions F4 and F5 were devoid of
cytotoxicity (IC(50)>100mug/ml) and displayed interesting
antileishmanial activity against the intracellular amastigote form of
the parasite (IC(50)=5.6 and 12.4mug/ml), respectively. However, the
antifungal activity observed for the crude extract could not be
recovered in the corresponding fractions.
PMID: 16212802
TITLE: Phlebotomine sandflies (Diptera: Psychodidae) of the Atlantic forest in
Recife, Pernambuco state, Brazil: the species coming to human bait, and their
seasonal and monthly variations over a 2-year period.
AUTHORS: V Q Balbino, I V Coutinho-Abreu, I V Sonoda, W Marques da Silva, C B
Marcondes
AFFILIATION: Department of Genetics, Federal University of Pernambuco, 50732-970
Recife, Pernambuco, Brazil.
REFERENCE: Ann Trop Med Parasitol 2005 Oct 99(7):683-93
In a study of the phlebotomine sandflies (Diptera: Psychodidae) in a
forest reserve in Recife, Pernambuco state, north-eastern Brazil, the
sandflies landing on human bait between 1.00 and 1.42 h after sunset
were collected weekly for 2 years. Although 10,287 sandflies of 10
Lutzomyia species were collected, almost all (96.5%) of the sandflies
caught were Lu. umbratilis. This species and several others caught are
potential vectors of some of the Leishmania parasites that cause human
disease. The recorded landing rate for Lu. umbratilis peaked, at the
high level of 333.3 flies/person-hour, during the collections made in
May 2003.The relative rarity in the collections of males of some of the
species caught probably indicates that these species do not lek on their
bloodmeal sources.It is likely that the sizes of the local populations
of species that are not very anthrophilic, such as Lu. flaviscutellata,
are much larger than indicated by the collections made on human bait.
PMID: 16196248
TITLE: Parsing parasites.
AUTHORS: Kaspar Mossman
REFERENCE: Sci Am 2005 Oct 293(4):29-30
PMID: 16230473
TITLE: Notch signaling is an important regulator of type 2 immunity.
AUTHORS: Lili Tu, Terry C Fang, David Artis, Olga Shestova, Seth E Pross, Ivan
Maillard, Warren S Pear
AFFILIATION: Department of Pathology and Laboratory Medicine, School of
Veterinary Medicine.
REFERENCE: J Exp Med 2005 Oct 202(8):1037-42
Notch ligands and receptors have been implicated in helper T cell (Th
cell) differentiation. Whether Notch signals are involved in
differentiation of T helper type 1 (Th1) cells, Th2 cells, or both,
however, remains unresolved. To clarify the role of Notch in Th cell
differentiation, we generated mice that conditionally inactivate Notch
signaling in mature T cells. Mice that lack Notch signaling in CD4(+) T
cells fail to develop a protective Th2 cell response against the
gastrointestinal helminth Trichuris muris. In contrast, they exhibit
effective Th1 cell responses and are able to control Leishmania major
infection. These data demonstrate that Notch signaling is a regulator of
type 2 immunity.
PMID: 16002315
TITLE: Analysis of ribosomal DNA internal transcribed spacer sequences of the
Leishmania donovani complex.
AUTHORS: Katrin Kuhls, Isabel L Mauricio, Francine Pratlong, Wolfgang Presber,
Gabriele Schönian
AFFILIATION: Institute of Microbiology and Hygiene (Parasitology), Charité
Universitätsmedizin Berlin, Dorotheenstr, 96, 10117 Berlin, Germany.
REFERENCE: Microbes Infect 2005 Aug 7(11-12):1224-34
To understand phylogenetic relationships of species and strains within
the Leishmania donovani complex, we have analyzed the ribosomal DNA
internal transcribed spacer (ITS) sequences of 27 Leishmania infantum, 2
Leishmania chagasi, 18 L. donovani and 5 Leishmania archibaldi strains
of different zymodemes and geographical origin. Eight ITS sequence types
were found. All detected sequence variation within ITS1 and ITS2 was
based on 12 polymorphic microsatellites. The L. infantum strains from
the Mediterranean region, China and L. chagasi from the New World formed
a phylogenetic group well separated from the second main group
including all strains from East Africa and India. Within the latter
group three distinct phylogenetic subgroups could be differentiated: (1
) L. donovani (Sudan/Ethiopia, China)+L. archibaldi (Sudan), (2) L.
donovani (Sudan/Ethiopia)+L. infantum (Sudan)+L. archibaldi (Sudan/
Ethiopia), and (3) L. donovani (Kenya, India). These groups are not
consistent with previous species definitions based on isoenzyme analyses
, e.g. L. infantum is polyphyletic and L. archibaldi is not supported as
a distinct species. Two groups of Indian strains could be
differentiated, one of which has an identical sequence type to the
strains from Kenya. Three main lineages of strains can thus be
differentiated in East Africa: two quite distantly related groups of
strains from Sudan/Ethiopia, and a third group including all strains
from Kenya, which is more closely related to part of the Indian strains
than to any of the Sudanese/Ethiopian groups. The ITS sequence analysis
presented here supports the need for revision of the taxonomy of the L.
donovani complex.
********************************************************************************************************************
The following references are revised files and are brought to you in accordance
to license agreement with the NLM.
********************************************************************************************************************
PMID: 12529367
TITLE: Role of peroxidoxins in Leishmania chagasi survival. Evidence of an
enzymatic defense against nitrosative stress.
AUTHORS: Stephen D Barr, Lashitew Gedamu
AFFILIATION: Department of Biological Sciences, University of Calgary, Alberta
T2N 1N4, Canada.
REFERENCE: J Biol Chem 2003 Mar 278(12):10816-23
The mechanisms by which Leishmania parasites survive exposure to highly
reactive oxygen (ROS) and nitrogen (RNS) species within phagosomes of
macrophages are not well known. Recently it has been shown that RNS
alone is sufficient and necessary to control Leishmania donovani
infection in mice (Murray, H. W., and Nathan, C. F. (1999) J. Exp. Med.
189, 741-746). No enzymatic defense against RNS has been discovered in
Leishmania to date. We have previously isolated two peroxidoxins (LcPxn1
and LcPxn2) from Leishmania chagasi and showed that recombinant LcPxn1
protein was capable of detoxifying hydrogen peroxide, hydroperoxide, and
hydroxyl radicals (Barr, S. D., and Gedamu, L. (2001) J. Biol. Chem.
276, 34279-34287). In further characterizing the physiological role of
peroxidoxins in Leishmania survival, we show here that recombinant
LcPxn1 protein can detoxify RNS in addition to ROS, whereas recombinant
LcPxn2 protein can only detoxify hydrogen peroxide. LcPxn1 and LcPxn2
are localized to the cytoplasm, and overexpression of LcPxn1 in L.
chagasi parasites enhanced survival when exposed to exogenous ROS and
RNS and enhanced survival within U937 macrophage cells. Site-directed
mutagenesis studies revealed that the conserved Cys-52 residue is
essential for detoxifying hydrogen peroxide, t-butyl hydroperoxide, and
hydroxyl radicals, whereas the conserved Cys-173 residue is essential
for detoxifying t-butyl hydroperoxide and peroxynitrite. This is the
first report of an enzymatic defense against RNS in Leishmania.
PMID: 12446214
TITLE: Specificity and kinetics of a mitochondrial peroxiredoxin of Leishmania
infantum.
AUTHORS: Helena Castro, Heike Budde, Leopold Flohé, Birgit Hofmann, Heinrich
Lünsdorf, Joseph Wissing, Ana M Tomás
AFFILIATION: Institute for Molecular and Cell Biology, Porto, Portugal.
REFERENCE: Free Radic Biol Med 2002 Dec 33(11):1563-74
In Kinetoplastida, comprising the medically important parasites
Trypanosoma brucei, T. cruzi, and Leishmania species, 2-Cys
peroxiredoxins described to date have been shown to catalyze reduction
of peroxides by the specific thiol trypanothione using tryparedoxin, a
thioredoxin-related protein, as an immediate electron donor. Here we
show that a mitochondrial peroxiredoxin from L. infantum (LimTXNPx) is
also a tryparedoxin peroxidase. In an heterologous system constituted by
nicotinamide adenine dinucleotide phosphate (NADPH), T. cruzi
trypanothione reductase, trypanothione and Crithidia fasciculata
tryparedoxin (CfTXN1 and CfTXN2), the recombinant enzyme purified from
Escherichia coli as an N-terminally His-tagged protein preferentially
reduces H(2)O(2) and tert-butyl hydroperoxide and less actively cumene
hydroperoxide. Linoleic acid hydroperoxide and phosphatidyl choline
hydroperoxide are poor substrates in the sense that they are reduced
weakly and inhibit the enzyme in a concentration- and time-dependent way
. Kinetic parameters deduced for LimTXNPx are a k(cat) of 37.0 s(-1) and
K(m) values of 31.9 and 9.1 microM for CfTXN2 and tert-butyl
hydroperoxide, respectively. Kinetic analysis indicates that LimTXNPx
does not follow the classic ping-pong mechanism described for other
TXNPx (Phi(1,2) = 0.8 s x microM(2)). Although the molecular mechanism
underlying this finding is unknown, we propose that cooperativity
between the redox centers of subunits may explain the unusual kinetic
behavior observed. This hypothesis is corroborated by high-resolution
electron microscopy and gel chromatography that reveal the native enzyme
to preferentially exist as a homodecameric ring structure composed of
five dimers.
PMID: 12446213
TITLE: Complementary antioxidant defense by cytoplasmic and mitochondrial
peroxiredoxins in Leishmania infantum.
AUTHORS: Helena Castro, Carla Sousa, Marta Santos, Anabela Cordeiro-da-Silva,
Leopold Flohé, Ana M Tomás
AFFILIATION: Institute for Molecular and Cell Biology, Porto, Portugal.
REFERENCE: Free Radic Biol Med 2002 Dec 33(11):1552-62
In Kinetoplastida 2-Cys peroxiredoxins are the ultimate members of
unique enzymatic cascades for detoxification of peroxides, which are
dependent on trypanothione, a small thiol specific to these organisms.
Here we report on two distinct Leishmania infantum peroxiredoxins,
LicTXNPx and LimTXNPx, that may be involved in such a pathway. LicTXNPx
, found in the cytoplasm, is a typical 2-Cys peroxiredoxin encoded by
LicTXNPx, a member of a multicopy gene family. LimTXNPx, encoded by a
single copy gene, LimTXNPx, is confined to the mitochondrion and is
unusual in possessing an Ile-Pro-Cys motif in the distal redox center,
replacing the common peroxiredoxin Val-Cys-Pro sequence, apart from an N
-terminal mitochondrial leader sequence. Based on sequence and
subcellular localization, the peroxiredoxins of Kinetoplastida can be
separated in two distinct subfamilies. As an approach to investigate the
function of both peroxiredoxins in the cell, L. infantum promastigotes
overexpressing LicTXNPx and LimTXNPx were assayed for their resistance
to H(2)O(2) and tert-butyl hydroperoxide. The results show evidence that
both enzymes are active as peroxidases in vivo and that they have
complementary roles in parasite protection against oxidative stress.
PMID: 11438539
TITLE: Cloning and characterization of three differentially expressed
peroxidoxin genes from Leishmania chagasi. Evidence for an enzymatic
detoxification of hydroxyl radicals.
AUTHORS: S D Barr, L Gedamu
AFFILIATION: Department of Biological Sciences, University of Calgary, Calgary,
Alberta T2N 1N4, Canada.
REFERENCE: J Biol Chem 2001 Sep 276(36):34279-87
Antioxidants have been implicated in protecting cells from oxygen
radicals produced as a result of aerobic metabolism and in response to
foreign pathogens by phagocytic cells. The mechanisms allowing pathogens
to withstand the toxic prooxidant environment within the phagolysosome
are poorly understood. We have cloned and characterized three
antioxidant genes belonging to the 2-Cys family of peroxidoxins from
Leishmania chagasi that may prove to provide these parasites with an
enhanced defense mechanism against toxic oxidants. The 5'-untranslated
regions and coding regions of each gene are highly conserved, whereas
the 3'-untranslated regions have diverged significantly. L. chagasi
peroxidoxin 1 (LcPxn1) is predominantly expressed in the amastigote
stage, whereas LcPxn2 and LcPxn3 are expressed mainly in the
promastigote stage, with LcPxn3 being far less abundant than LcPxn2.
LcPxn2 and LcPxn3 possess a nine-amino acid extension at the carboxyl
terminus, which LcPxn1 lacks. LcPxn1 appears to exist as high molecular
weight multimers in vivo, and recombinant LcPxn1 was shown to detoxify
hydrogen peroxide and alkyl hydroperoxides. We also present strong
evidence that recombinant LcPxn1 can enzymatically detoxify hydroxyl
radicals, an activity never before clearly demonstrated for a protein.
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