Multidrug resistant tuberculosis co-existing with aspergilloma and invasive aspergillosis in a 50 year old diabetic woman: a case report

Aspergilloma and invasive aspergillosis coexisting with multidrug resistant Mycobacterium tuberculosis (MDR-TB) in the same patient is a rare entity. We report a 50 year old South Indian woman, a diabetic, who presented to us with complaints of productive cough and hemoptysis for the past 2 months. She was diagnosed to have pulmonary tuberculosis 2 years ago for which she took irregular treatment. Lung imaging showed features of a thick walled cavity in the right upper lobe with an indwelling aspergilloma. She underwent a right lung upper lobe resection. Biopsy and culture of the resected specimen showed the coexistence of Aspergillus fumigatus and multi-drug resistant Mycobacterium tuberculosis. 2 blood cultures grew Aspergillus fumigatus. She was successfully treated with Voriconazole and anti tuberculous therapy against MDR-TB

Identification and Characterization of an Unusual Class I Myosin Involved in Vesicle Traffic in Trypanosoma brucei

Myosins are a multimember family of motor proteins with diverse functions in eukaryotic cells. African trypanosomes possess only two candidate myosins and thus represent a useful system for functional analysis of these motors. One of these candidates is an unusual class I myosin (TbMyo1) that is expressed at similar levels but organized differently during the life cycle of Trypanosoma brucei. This myosin localizes to the polarized endocytic pathway in bloodstream forms of the parasite. This organization is actin dependent. Knock down of TbMyo1 results in a significant reduction in endocytic activity, a cessation in cell division and eventually cell death. A striking morphological feature in these cells is an enlargement of the flagellar pocket, which is consistent with an imbalance in traffic to and from the surface. In contrast TbMyo1 is distributed throughout procyclic forms of the tsetse vector and a loss of ∼90% of the protein has no obvious effects on growth or morphology. These results reveal a life cycle stage specific requirement for this myosin in essential endocytic traffic and represent the first description of the involvement of a motor protein in vesicle traffic in these parasites

The streamlined genome of Phytomonas spp. relative to human pathogenic kinetoplastids reveals a parasite tailored for plants

Members of the family Trypanosomatidae infect many organisms, including animals, plants and humans. Plant-infecting trypanosomes are grouped under the single genus Phytomonas, failing to reflect the wide biological and pathological diversity of these protists. While some Phytomonas spp. multiply in the latex of plants, or in fruit or seeds without apparent pathogenicity, others colonize the phloem sap and afflict plants of substantial economic value, including the coffee tree, coconut and oil palms. Plant trypanosomes have not been studied extensively at the genome level, a major gap in understanding and controlling pathogenesis. We describe the genome sequences of two plant trypanosomatids, one pathogenic isolate from a Guianan coconut and one non-symptomatic isolate from Euphorbia collected in France. Although these parasites have extremely distinct pathogenic impacts, very few genes are unique to either, with the vast majority of genes shared by both isolates. Significantly, both Phytomonas spp. genomes consist essentially of single copy genes for the bulk of their metabolic enzymes, whereas other trypanosomatids e.g. Leishmania and Trypanosoma possess multiple paralogous genes or families. Indeed, comparison with other trypanosomatid genomes revealed a highly streamlined genome, encoding for a minimized metabolic system while conserving the major pathways, and with retention of a full complement of endomembrane organelles, but with no evidence for functional complexity. Identification of the metabolic genes of Phytomonas provides opportunities for establishing in vitro culturing of these fastidious parasites and new tools for the control of agricultural plant disease. © 2014 Porcel et al

Isavuconazole for the treatment of invasive aspergillosis and mucormycosis: current evidence, safety, efficacy, and clinical recommendations

Suganthini Krishnan Natesan,1,2 Pranatharthi H Chandrasekar1 1Division of Infectious Diseases, Department of Internal Medicine, Wayne State University, 2John D Dingell VA Medical Center, Detroit, MI, USA Abstract: The majority of invasive mold infections diagnosed in immunocompromised cancer patients include invasive aspergillosis (IA) and mucormycosis. Despite timely and effective therapy, mortality remains considerable. Antifungal agents currently available for the management of these serious infections include triazoles, polyenes, and echinocandins. Until recently, posaconazole has been the only triazole with a broad spectrum of anti-mold activity against both Aspergillus sp. and mucorales. Other clinically available triazoles voriconazole and itraconazole, with poor activity against mucorales, have significant drug interactions in addition to a side effect profile inherent for all triazoles. Polyenes including lipid formulations pose a problem with infusion-related side effects, electrolyte imbalance, and nephrotoxicity. Echinocandins are ineffective against mucorales and are approved as salvage therapy for refractory IA. Given that all available antifungal agents have limitations, there has been an unmet need for a broad-spectrum anti-mold agent with a favorable profile. Following phase III clinical trials that started in 2006, isavuconazole (ISZ) seems to fit this profile. It is the first novel triazole agent recently approved by the United States Food and Drug Administration (FDA) for the treatment of both IA and mucormycosis. This review provides a brief overview of the salient features of ISZ, its favorable profile with regard to spectrum of antifungal activity, pharmacokinetic and pharmacodynamic parameters, drug interactions and tolerability, clinical efficacy, and side effects. Keywords: isavuconazole, aspergillosis, mucormycosis, efficacy, antifungal therapy, novel azole, tolerability, drug interaction

Stromules: a characteristic cell-specific feature of plastid morphology.

Stromules (stroma-filled tubules) are highly dynamic structures extending from the surface of all plastid types examined so far, including proplastids, chloroplasts, etioplasts, leucoplasts, amyloplasts, and chromoplasts. Stromules are usually 0.35-0.85 microm in diameter and of variable length, from short beak-like projections to linear or branched structures up to 220 mum long. They are enclosed by the inner and outer plastid envelope membranes and enable the transfer of molecules as large as Rubisco (approximately 560 kDa) between interconnected plastids. Stromules occur in all cell types, but stromule morphology and the proportion of plastids with stromules vary from tissue to tissue and at different stages of plant development. In general, stromules are more abundant in tissues containing non-green plastids, and in cells containing smaller plastids. The primary function of stromules is still unresolved, although the presence of stromules markedly increases the plastid surface area, potentially increasing transport to and from the cytosol. Other functions of stromules, such as transfer of macromolecules between plastids and starch granule formation in cereal endosperm, may be restricted to particular tissues and cell types

Myosin XI is required for actin-associated movement of plastid stromules.

Stromules are highly dynamic stroma-filled tubules extending from the surface of plastids and occasionally interconnecting individual plastids, allowing the movement of complex biological molecules between the interconnected plastids. Experiments with inhibitors of cytoskeleton assembly have indicated the involvement of an actin-based system in stromule movement. However, the motor protein associated with the system had not been identified. Here, we present direct evidence that myosin XI is involved in the formation and movement of stromules in tobacco leaves. Application of 2,3-butanedione 2-monoxime, an inhibitor of myosin ATPase activity, resulted in the loss of stromules from tobacco leaf epidermal cells. Transient RNA interference of myosin XI in leaves of Nicotiana benthamiana also resulted in the loss of stromules from epidermal cells, without any effect on transcripts for actin or myosin VIII. Transient expression of a GFP-tagged myosin XI tail domain in tobacco leaf epidermal cells showed that the fusion protein localized to the chloroplast envelope, as well as to mitochondria and other organelles. Our findings identify myosin XI as a key protein involved in the formation and movement of stromules

Intracellular trafficking in the trypanosomatids.

Trypanosomes are members of the kinetoplastida, a group of divergent protozoan parasites responsible for considerable morbidity and mortality worldwide. These organisms have highly complex life cycles requiring modification of their cell surface together with engagement of immune evasion systems to effect survival; both processes intimately involve the membrane trafficking system. The completion of three trypanosomatid and several additional protist genomes in the last few years is providing an exciting opportunity to evaluate, at the molecular level, the evolution and diversity of membrane trafficking across deep evolutionary time as well as to analyse in unprecedented detail the membrane trafficking systems of trypanosomes

TbVps34, the trypanosome orthologue of Vps34, is required for Golgi complex segregation.

Phosphoinositides are important regulators of numerous cellular functions. The yeast class III phosphatidylinositol 3-kinase Vps34p, and its human orthologue hVPS34, are implicated in control of several key pathways, including endosome to lysosome transport, retrograde endosome to Golgi traffic, multivesicular body formation, and autophagy. We have identified the Vps34p orthologue in the African trypanosome, TbVps34. Knockdown of TbVps34 expression by RNA interference induces a severe growth defect, with a post-mitotic block to cytokinesis accompanied by a variety of morphological abnormalities. GFP2xFYVE, a chimeric protein that specifically binds phosphatidylinositol 3-phosphate, localizes to the trypanosome endosomal system and is delocalized under TbVps34 RNA interference (RNAi), confirming that TbVps34 is an authentic phosphatidylinositol 3-kinase. Expression of GFP2xFYVE enhances the TbVps34 RNAi-associated growth defect, suggesting a synthetic interaction via competition for phosphatidylinositol 3-phosphate-binding sites with endogenous FYVE domain proteins. Endocytosis of a fluid phase marker is unaffected by TbVps34 RNAi, but receptor-mediated endocytosis of transferrin and transport of concanavalin A to the lysosome are both impaired, confirming a role in membranous endocytic trafficking for TbVps34. TbVps34 knockdown inhibits export of variant surface glycoprotein, indicating a function in exocytic transport. Ultrastructural analysis revealed a highly extended Golgi apparatus following TbVps34 RNAi, whereas expression of the Golgi marker red fluorescent protein-GRASP (Grp1 (general receptor for phosphoinositides-1)-associated scaffold protein) demonstrated that trypanosomes are able to duplicate the Golgi complex but failed to complete segregation during mitosis, despite faithful replication and segregation of basal bodies and the kinetoplast. These observations implicate TbVps34 as having a role in coordinating segregation of the Golgi complex at cell division

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Not AvailableBrucellosis in pigs, caused by the bacterium Brucella suis, is an important zoonotic infection. In the present study, fluorescence polarization assay (FPA) was standardized and compared with indirect enzyme linked immunosorbent assay (iELISA) and competitive ELISA (cELISA) for diagnosis of porcine brucellosis. Test performances were evaluated using representative panel (n = 100), samples from swine brucellosis outbreak (n = 300), samples from brucellosis suspected animals (n = 291) and sera samples from apparently healthy animals (n = 1121). With panel samples, the FPA cut-off ≥11ΔmP was arrived with sensitivity (Se) and specificity (Sp) of 95.00 and 98.75%, respectively. Testing of samples from swine brucellosis outbreak, the diagnostic Se and Sp of 100 and 95.14% by iELISA, 73.91 and 100% by cELISA and 86.96 and 100% by FPA, respectively were recorded. Similarly, in case of swine brucellosis suspected samples, relative performance of FPA with cELISA had revealed higher kappa value of 0.864 with an accuracy of 93.47. Indirect ELISA was found to be highly sensitive but showed cross reactivity mainly for Yersinia enterocolitica O9 antibodies than cELISA and FPA. The high specificity of FPA test recorded in various types of samples in the study indicated that, FPA could serve as confirmatory test for individual animal diagnosis, outbreak confirmation, surveillance and quarantine of swine brucellosis cases.Not Availabl