In This Issue
BIOCHEMISTRY
Tuberculosis' missing link
Mycobacterium tuberculosis and other mycobacteria synthesize extremely long-chain fatty acids for inclusion in their protective shell. Attacking the fatty acid elongation pathway has been an effective way of treating tuberculosis, even though some of the enzymes of the pathway have remained unknown. Emmanuelle Sacco et al. identified the missing piece of the M. tuberculosis type II fatty acid synthase system. The authors began with an in silico strategy to identify candidate genes. One set of candidates produced two heterodimers: HadAB and HadBC, both of which had the desired enzymatic characteristic of high affinity for long-chain and acyl carrier protein-linked fatty acids. When added to other proteins of the mycobacterial fatty acid synthase system, the mixture displayed the expected dehydratase activity. The authors say that these two enzymes are the missing link in the mycobacterial fatty acid elongation pathway. The structure of these enzymes is distinct from that of the classical enzymes possessing a homologous function in other bacteria. Identification of proteins that are essential for mycobacteria survival opens new avenues for antimycobacterial drug development. — P.D.
“The missing piece of the type II fatty acid synthase system from Mycobacterium tuberculosis” by Emmanuelle Sacco, Adrian Suarez Covarrubias, Helen M. O'Hare, Paul Carroll, Nathalie Eynard, T. Alwyn Jones, Tanya Parish, Mamadou Daffé, Kristina Bäckbro, and Annaïk Quémard (see pages 14628–14633)
BIOPHYSICS
A friction limit on phage DNA ejection
Phages infect bacteria by injecting DNA under high pressure. Biophysicists have measured DNA translocation rates as high as 70 kbp/s. In single-phage experiments, Paul Grayson et al. observed DNA ejection in real time to characterize the forces involved. They report that, in phage λ, the ejection force depends almost wholly on the amount of DNA remaining in the capsid and is balanced by a frictional force similar to hydrodynamic drag. The authors immobilized phages in a flow cell and induced DNA ejection. Fluorescent DNA-staining dye made ejection traces immediately visible. The authors obtained curves for two strains of phage: one with a genome length of 38 kbp and the other with a genome length of 48.5 kbp. The ejection follows a parabola-like curve, with an initial value of 20 kbp/s rising to a maximum of 60 kbp/s before tailing to zero when all DNA is spent. Ejection speeds, plotted against DNA remaining, are similar for the two phage strains. On the basis of an estimate of packing forces, the authors show that friction from DNA–DNA interactions is 100 times greater when the capsid is full than when it is empty. The same physics should apply to DNA ejection across all phage species. — K.M.
Phage DNA ejection traces.
“Real-time observations of single bacteriophage λ DNA ejections in vitro” by Paul Grayson, Lin Han, Tabita Winther, and Rob Phillips (see pages 14652–14657)
GENETICS
Genome-wide search for Crohn's disease genes
Crohn's disease is an inflammatory bowel disorder that has a genetic component, as well as dietary and environmental factors. These complex origins have made it difficult for scientists to identify patients at risk and to pinpoint targets for drug therapy. John Raelson et al. now report the results of a genome-wide association (GWA) study that identifies several Crohn-linked genes and confirms those previously known. The authors relied on data from the Quebec Founder Population (QFP), a genetically isolated group descended from settlers who emigrated from France to Quebec in the 1500s. A GWA study was performed on 382 parent–parent–child Crohn trios from the QFP by examining 164,000 evenly spaced chromosomal locations to identify disease-associated regions. After the initial scan, the authors carried out fine mapping at higher density, using additional QFP samples. For verification in an independent German population, 16 loci were tested, of which 7 were confirmed. Three of these, NOD2, IBD5, and IL23R, were known previously, and four additional loci were found, one each on chromosomes 3 and 4 and two on chromosome 17. The mutated Crohn genes identified to date are important regulators of epithelial defense, tissue repair, and both active and innate immune response. — K.M.
Cellular localization of IL23R in human colon.
“Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci” by John V. Raelson, Randall D. Little, Andreas Ruether, Hélène Fournier, Bruno Paquin, Paul Van Eerdewegh, W. E. C. Bradley, Pascal Croteau, Quynh Nguyen-Huu, Jonathan Segal, Sophie Debrus, René Allard, Philip Rosenstiel, Andre Franke, Gunnar Jacobs, Susanna Nikolaus, Jean-Michel Vidal, Peter Szego, Nathalie Laplante, Hilary F. Clark, René J. Paulussen, John W. Hooper, Tim P. Keith, Abdelmajid Belouchi, and Stefan Schreiber (see pages 14747–14752)
PLANT BIOLOGY
LOV1 plant resistance gene confers susceptibility to fungus
Plant resistance genes are attractive targets for gene transfer experiments and crop bioengineering because they potentially enable scientists to create plants that can survive many types of diseases. The major class of these genes encodes proteins that contain nucleotide-binding sites and leucine-rich repeat regions (NBS-LRR), and they are similar to proteins such as Toll/interleukin 1 receptors that regulate innate immunity in animals. Jennifer Lorang et al. found that one such plant gene, LOV1, makes the mustard-related plant Arabidopsis thaliana susceptible to the Victoria blight fungus, Cochliobolus victoriae. After mapping and cloning the gene, the authors observed that LOV1 mediated responses associated with plant defense, including the induction of pathogenicity-related genes and cellular necrosis, in response to the fungal peptide, victorin. However, this interaction conferred susceptibility instead of producing resistance; the fungus penetrated further into the plant after the initial round of cell death. Genes encoding NBS-LRR proteins can condition disease susceptibility, as well as resistance, and thus have implications for the deployment of resistance genes in bioengineered plants, the authors say. — F.A.
Disease susceptibility conferred by the LOV1 gene.
“Plant disease susceptibility conferred by a ‘resistance’ gene” by Jennifer M. Lorang, Teresa A. Sweat, and Thomas J. Wolpert (see pages 14861–14866)
POPULATION BIOLOGY
Toxoplasma's shared heritage
Toxoplasma gondii is one of the world's most common protozoan parasites, infecting many warm-blooded vertebrates and 25% of the human population. Asis Khan et al. report that its success may be explained by a single monomorphic chromosome that has swept rapidly through worldwide populations in the last 10,000 years. The authors sequenced genomic regions from the most common Toxoplasma strains of North and South America and Europe. Strains from North America and Europe are very similar, whereas independent polymorphisms with greater diversity appear in South America. Khan et al. suggest that the initial divergence between northern and southern strains occurred ≈1–2 million years ago, when members of the cat family arrived in South America carrying Toxoplasma. A striking exception was a single chromosome shared by nearly all northern strains, and many southern ones, that appeared ≈10,000 years ago. The authors suggest that some of the ≈120 genes on this chromosome conveyed a strong selective advantage and may be responsible for Toxoplasma's ability to infect, and may be transmitted by, many different animals across the world. Further studies of Toxoplasma's genes may reveal the basis of this success and why different strains can cause different clinical symptoms. — P.D.
Toxoplasma replicating within its host.
“Recent transcontinental sweep of Toxoplasma gondii driven by a single monomorphic chromosome” by A. Khan, B. Fux, C. Su, J. P. Dubey, M. L. Darde, J. W. Ajioka, B. M. Rosenthal, and L. D. Sibley (see pages 14872–14877)
