In the arms race of bacterial pathogenesis, bacteria produce an array of toxins and virulence factors that disrupt host processes while hosts respond with immune countermeasures. One key virulence mediator of the ubiquitous, opportunistic, extracellular pathogen Pseudomonas aeruginosa is the iron-binding siderophore pyoverdin (PMID:10722571;PMID: 8550201). The mechanisms used by pyoverdin to acquire iron from the host remain incompletely elucidated. Here we demonstrate that mitochondria represent an important target for iron acquisition and that exposure to this toxin results in loss of mitochondrial membrane potential, altered mitochondrial dynamics, and mitophagy in both Caenorhabditis elegans and mammalian cells. We also show that animal mitophagy protects the consequences of siderophore activity, conferring resistance to pyoverdin-mediated host killing. In C. elegans, the conserved autophagic genes bec-1/BECN1 and lgg-1/LC3, and the mitophagic regulator pink-1/PINK1 are required for iron chelator-elicited mitochondrial turnover and provide protection against iron sequestration by P. aeruginosa, likely by ameliorating the mitochondrial damage. While autophagic mechanisms have been implicated in the destruction of intracellular bacteria via a process called xenophagy (PMID: 24005326), our findings represent the first report of resistance to an extracellular pathogen being conferred by authentic autophagic activity that targets host organelles.
A conserved mitochondrial surveillance pathway is required for defense against Pseudomonas aeruginosa.
Specimen part, Treatment
View SamplesPseudomonas aeruginosa is a re-emerging opportunistic pathogen with broad antimicrobial resistance. We have previously reported that the major siderophore pyoverdine from this pathogen disrupts mitochondrial networks and induces a lethal hypoxic response in model host Caernorhabditis elegans. However, the mechanism of such cytotoxicity remained unclear. Here, we demonstrate that pyoverdine translocates into host cells, binding to host ferric iron sources. The reduction of host iron content disrupts mitochondrial function such as NADH oxidation and ATP production and activates mitophagy. This activates a specific immune response that is distinct from colonization-based pathogensis and exposure to downstream pyoverdine effector Exotoxin A. Host response to pyoverdine resembles that of a hypoxic crisis or iron chelator treatment. Furthermore, we demonstrate that pyoverdine is a crucial virulence factor in P. aerguinosa pathogenesis against cystic fibrosis patients; F508 mutation in human CFTR increases susceptibility to pyoverdine-mediated damage.
Pyoverdine, a siderophore from Pseudomonas aeruginosa, translocates into C. elegans, removes iron, and activates a distinct host response.
Specimen part, Treatment
View SamplesPseudomonas aeruginosa is an opportunistic pathogen that causes severe health problems. Despite intensive investigation, many aspects of microbial virulence remain poorly understood. We used a high-throughput, high-content, whole-organism, phenotypic screen to identify small molecules that inhibit P. aeruginosa virulence in C. elegans. Approximately half of the hits were known antimicrobials. A large number of hits were non-antimicrobial bioactive compounds, including the cancer chemotherapeutic 5-fluorouracil. We determined that 5-fluorouracil both transiently inhibits bacterial growth and reduces pyoverdine biosynthesis. Pyoverdine is a siderophore that regulates the expression of several virulence determinants and is critical for pathogenesis in mammals. We show that 5-fluorouridine, a downstream metabolite of 5-fluorouracil, is responsible for inhibiting pyoverdine biosynthesis. We also show that 5-fluorouridine, in contrast to 5-fluorouracil, is a genuine anti-virulent compound, with no bacteriostatic or bacteriocidal activity. To our knowledge, this is the first report utilizing a whole-organism screen to identify novel compounds with antivirulent properties effective against P. aeruginosa.
A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence.
Specimen part, Treatment
View SamplesMutants in the imprinted PICKLE RELATED 2 gene, suppress seed abortion of fertilization independent seed class mutants and paternal excess interploidy crosses in Arabidopsis
No associated publication
Specimen part
View SamplesLeaf rate elongation is extremely sensitive to soil water status.
Transcriptome profiling of leaf elongation zone under drought in contrasting rice cultivars.
Specimen part, Treatment
View SamplesRice deletion mutants have not been widely used in functional genomics, because the mutated genes are not tagged and therefore, difficult to identify
Detection of genomic deletions in rice using oligonucleotide microarrays.
Specimen part
View SamplesLeaves and panicles from recurrent parent KMR3 and a high yielding KMR3-O.rufipogon introgression line were used
Os11Gsk gene from a wild rice, Oryza rufipogon improves yield in rice.
Specimen part
View SamplesWe exposed Kavya rice seedlings to different gall midge biotypes, GMB1 and GMB4M, which exhibit incompatible and compatible interactions, respectively.
A novel mechanism of gall midge resistance in the rice variety Kavya revealed by microarray analysis.
Specimen part
View SamplesOsPSTOL1 confers phosphorus (P)-deficiency tolerance in rice through enhancement of early root growth. The larger root surface area at early stage provides the plants an advantage for nutrient uptake.
The protein kinase Pstol1 from traditional rice confers tolerance of phosphorus deficiency.
Specimen part
View SamplesBph6 is a gene that confers rice high resistance to its devastating pest BPH. Understanding the molecular responses of the resistant and susceptible varieties would pave the way to controlling the pest more effectively.
No associated publication
Specimen part
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