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[
J Med Microbiol,
2013]
Stenotrophomonas maltophilia plays an important role as an opportunistic pathogen in immunocompromised individuals. Despite its clinical implication, the true knowledge regarding the pathogenicity of these bacteria remains unclear. Various methods have been employed to prove this bacterium to be pathogenic. However, the debate whether S. maltophilia is a true pathogen or a colonizer still remains unanswered as effective killing was not seen in earlier experiments with different animal models of infection (Denton et al., 1998; Adamak et al., 2011; Pompilo et al., 2011). Study by Rouf et al. (2011) on murine lung infection model illustrated that different strains of mice exhibited different outcome for S. maltophilia infection. Strains such as A/J and DBA/2 were permissive for clinical isolates of S. maltophilia and showed higher levels of pro-inflammatory cytokines. In contrast, BALB/c and C57BL/6 strains were non-permissive for S. maltophilia. While Huang et al. (2009) showed nematotoxic activity by environmental S. maltophilia strain against free-living nematode, Panagrellus redivivus, and plant-parasitic nematode, Bursaphelenchus xylophilus.
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Kim J, Park J, Bae E, Shong M, Kim JM, Lee SB, Kim Y, Song S, Lee S, Kim S, Chung J
[
Nature,
2006]
Autosomal recessive juvenile parkinsonism (AR-JP) is an early-onset form of Parkinson''s disease characterized by motor disturbances and dopaminergic neurodegeneration. To address its underlying molecular pathogenesis, we generated and characterized loss-of-function mutants of Drosophila PTEN-induced putative kinase 1 (PINK1), a novel AR-JP-linked gene. Here, we show that PINK1 mutants exhibit indirect flight muscle and dopaminergic neuronal degeneration accompanied by locomotive defects. Furthermore, transmission electron microscopy analysis and a rescue experiment with Drosophila Bcl-2 demonstrated that mitochondrial dysfunction accounts for the degenerative changes in all phenotypes of PINK1 mutants. Notably, we also found that PINK1 mutants share marked phenotypic similarities with parkin mutants. Transgenic expression of Parkin markedly ameliorated all PINK1 loss-of-function phenotypes, but not vice versa, suggesting that Parkin functions downstream of PINK1. Taken together, our genetic evidence clearly establishes that Parkin and PINK1 act in a common pathway in maintaining mitochondrial integrity and function in both muscles and dopaminergic neurons.
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[
Nature,
2006]
Parkinson''s disease is the second most common neurodegenerative disorder and is characterized by the degeneration of dopaminergic neurons in the substantia nigra. Mitochondrial dysfunction has been implicated as an important trigger for Parkinson''s disease-like pathogenesis because exposure to environmental mitochondrial toxins leads to Parkinson''s disease-like pathology. Recently, multiple genes mediating familial forms of Parkinson''s disease have been identified, including PTEN-induced kinase 1 (PINK1; PARK6) and parkin (PARK2), which are also associated with sporadic forms of Parkinson''s disease. PINK1 encodes a putative serine/threonine kinase with a mitochondrial targeting sequence. So far, no in vivo studies have been reported for pink1 in any model system. Here we show that removal of Drosophila PINK1 homologue (CG4523; hereafter called pink1) function results in male sterility, apoptotic muscle degeneration, defects in mitochondrial morphology and increased sensitivity to multiple stresses including oxidative stress. Pink1 localizes to mitochondria, and mitochondrial cristae are fragmented in pink1 mutants. Expression of human PINK1 in the Drosophila testes restores male fertility and normal mitochondrial morphology in a portion of pink1 mutants, demonstrating functional conservation between human and Drosophila Pink1. Loss of Drosophila parkin shows phenotypes similar to loss of pink1 function. Notably, overexpression of parkin rescues the male sterility and mitochondrial morphology defects of pink1 mutants, whereas double mutants removing both pink1 and parkin function show muscle phenotypes identical to those observed in either mutant alone. These observations suggest that pink1 and parkin function, at least in part, in the same pathway, with pink1 functioning upstream of parkin. The role of the pink1-parkin pathway in regulating mitochondrial function underscores the importance of mitochondrial dysfunction as a central mechanism of Parkinson''s disease pathogenesis.
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[
FEMS Microbiol Lett,
2008]
The role of periplasmic disulfide oxidoreductase DsbA in Shiga toxin-producing Escherichia coli O157:H7 (STEC) was investigated. Deletion of dsbA (DeltadsbA) significantly decreased cell motility and alkaline phosphatase activity in STEC. STEC DeltadsbA also showed greater sensitivity to menadione and under low pH conditions. Significant reductions in surface attachment to both biotic (HT-29 epithelial cells) and abiotic (polystyrene and polyvinyl chloride) surfaces were observed in STEC DeltadsbA. In addition, no biofilm formation was detected in STEC DeltadsbA compared to wild-type cells in glass capillary tubes under continuous flow-culture system conditions. In the nematode model Caenorhabditis elegans-killing assay, the deletion of dsbA in STEC resulted in attenuated virulence compared to wild-type cells. STEC DeltadsbA was also found to have a reduced ability to colonize the nematode gut. These results suggest that DsbA plays important roles in biofilm formation and virulence in STEC cells.
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[
FEMS Microbiol Lett,
2008]
In vitro mimicking of the stimuli controlling in vivo-inducible bacterial promoters during infection of the host can be complex. Therefore, the use of the nematode Caenorhabditis elegans was evaluated, as a surrogate host to examine the expression of Salmonella enterica promoters. Green fluorescent protein (GFP+) was put under the control of the promoters of the pagC, mgtB, sseA, pgtE and fur genes of S. enterica. After infection of C. elegans with an S. enterica serovar Typhimurium vaccine strain expressing these constructs, clear bacterial expression of GFP+ was observed under the control of all five promoters, although significant expression was not always obtained in vitro. It is concluded that C. elegans constitutes a useful model system for the study of the in vivo expression of Salmonella promoters.
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[
J Biomol NMR,
2004]
The Northeast Structural Genomics Consortium (NESG) is a pilot project designed to evaluate the feasibility and value of structural genomics. The 21 kDa Caenorhabditis elegans protein coded by gene CE32E8.3 (TrEMBL protein P91127, referred to here as WR33) is one of several hundred targets identified for structural analysis by the Northeast Structural Genomics Consortium (www.nesg.org). WR33 belongs to a large protein domain family with homologues in several eukaryotic genomes, including those of Homo sapiens (TrEMBL proteins Q9Y326, O94811, and Q9Y6H0), Mus musculis (TrEMBL protein Q9CRB6), and Drosophila melanogaster (TrEMBL protein Q(VV43). The 25 kDa Bos Taurus (bovine) homologue from this family (Q27957), with 38% sequence identity with WR33 over 175 residues, is characterized as 'brain specific protein P25' (Shiratsuchi et al., 1995) and is expressed in oligodendrocytes and neutrophils of bovine brain tissue. However, none of the members of this strongly conserved protein domain family has a characterized biological function.