Links to Other ASM Pages:



• Table of Contents
• ASM News Issues

Journal Highlights

Yeast Prions Require Chaperone to Spread

Wegrzyn, Chernoff, and Newman (l to r)

Prions are different from other aggregating proteins because they are infectious (in mammals) and transmissible by cytoplasm (in yeast). Yury O. Chernoff and colleagues of Georgia Institute of Technology, Atlanta, show that a cellular protein, chaperone Hsp104, makes prions transmissible in yeast by enabling aggregates to dissociate into small "seeds" which initiate new aggregates. "Aggregates are like molecular tumors," says Chernoff. "Those that cannot dissociate are like nonmalignant tumors, while those that dissociate into seeds are like metastatic tumors."

"Targeting the Hsp104-equivalent factors in mammals could be used to counteract prion infectivity," says Chernoff. But first, Chernoff plans to investigate whether Hsp104 functional equivalents exist in mammals, as well as the mechanism by which prions interact with Hsp104 to produce "seeds."

(R. D. Wegrzyn, K. Bapat, G. P. Newnam, A. D. Zink, and Y. O. Chernoff. 2001. Mechanism of prion loss after Hsp104 inactivation in yeast. Mol. Cell. Biol. 21:4656-4669.) Abstract | Full Text

Quorum-Sensing Molecule Blocks Conversion to Pathogenic Morphology in Candida

Wegrzyn, Chernoff, and Newman (l to r)

Candida spp. have become the fourth leading cause of nosocomial infections. Mortality rates approach 50% for systemic candidiasis. Normally resident in the intestine, Candida becomes pathogenic when it morphs from yeast into mycelia. Systemic candidiasis is difficult to treat, largely due to a lack of effective antifungal agents. Candida cell morphology is dependent on cell density, which is controlled by quorum-sensing molecules. In the first demonstration of quorum sensing in eukaryotes, Kenneth W. Nickerson of the University of Nebraska, Omaha, and others identify farnesol as a quorum-sensing molecule. But questions remain. Is this the only quorum-sensing molecule? The main quorum-sensing molecule? "We have high hopes for the therapeutic potential of farnesol analogs," says Nickerson. "We are currently exploring farnesol's mode of action."

(J. M. Hornby, E. C. Jensen, A. D. Lisec, J. J. Tasto, B. Jahnke, R. Shoemaker, P. Dussault, and K. W. Nickerson. 2001. Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol. Appl. Environ. Microbiol. 67:2982-2992.) Abstract | Full Text

Another Step towards HIV Vaccine

Researchers so far have failed to design an HIV vaccine that reliably elicits strong, broadly reactive neutralizing antibodies to primary HIV isolates. The one optimistic finding has been isolation of several human monoclonal antibodies with good neutralizing properties. The problem now is how to make an immunogen that will induce such antibodies. Now, a team from Simon Fraser University, British Columbia, Canada, and The Scripps Research Institute, La Jolla, Calif., has taken the first step in that direction, with the identification of a synthetic peptide ligand, B2.1, of one such monoclonal antibody, b12. The next step, says PI Jamie Scott of Simon Fraser, will be an attempt to boost b12-like antibody production. The group will prime animals with gp120 linked to a carrier protein that bears strong helper T-cell epitopes, and then boost using the same complex, but with B2.1 replacing gp120. They are developing several peptide ligands to target three other broadly neutralizing antibodies.

(M. B. Zwick, L. L. C. Bonnycastle, A. Menendez, M. B. Irving, C. F. Barbas III, P. W. H. I. Parren, D. R. Burton, and J. K. Scott. 2001. Identification and characterization of a peptide that specifically binds the human, broadly neutralizing anti-human immunodeficiency virus type 1 antibody b12. J. Virol. 75:6692-6699.) Abstract | Full Text

Mapping Induction of Free Radical Defenses

Zheng

Reactive oxygen species can damage cells and contribute to several degenerative diseases. They also induce defensive responses in cells. Gisela Storz of the National Institutes of Health, Bethesda, Md., and others showed previously that in Escherichia coli, the key regulator of defenses against H₂O₂ is the OxyR transcription factor. This group has now used microarrays to identify genes most highly induced by H2O2 and to determine which are regulated by OxyR. "We found that OxyR regulates most of the highly induced genes," says Storz. We identified several new OxyR-activated genes, including one whose products may participate in Fe-S cluster assembly or repair. We also found some induced genes that are OxyR independent." In a concurrently published paper, using a computational approach to search the E. coli genome, the group identifies more OxyR target genes. "The combined results [of the two papers] indicate that response to H₂O₂ is tightly coordinated with the regulation of iron homeostasis," says Storz. "This makes sense, since H2O2's toxicity is largely due its reaction with iron, which generates hydroxyl radical."

(M. Zheng, X. Wang, L. J. Templeton, D. R. Smulski, R. A. LaRossa, and G. Storz. 2001. DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide. J. Bacteriol. 183:4562-4570.) Abstract | Full Text

Sixteen Penicillin and MDR Pneumo Clones Characterized, Named

McGee

Emergence of penicillin- and multidrug-resistant pneumococcal strains has become a global concern. The Pneumococcal Molecular Epidemiology Network was established in 1997 under the International Union of Microbiological Societies to provide guidelines to characterize and name these antibiotic-resistant pneumococcal clones in order to track their progress and identify the social and biological reasons for their success. Now, L. McGee of the South African Institute for Medical Research, Johannesburg, and others describe the first 16 clones accepted into the Network, based on epidemiological criteria and BOX-PCR, PFGE, and MLST fingerprinting, and provide a standard nomenclature. "The clones are available through the ATCC," says McGee. "The Network meets annually at ICAAC and will continue to classify new clones as they are identified. The Network can serve as a prototype for collaboration to identify clones of important human pathogens, and as a model for other networks." (See Current Topics, p. 435.)

(L. McGee, L. McDougal, J. Zhou, B. G. Spratt, F. C. Tenover, R. George, R. Hakenbeck, W. Hryniewicz, J. C. Lefevre, A. Tomasz, and K. P. Klugman. 2001. Nomenclature of major antimicrobial-resistant clones of Streptococcus pneumoniae defined by the pneumococcal molecular epidemiology network. J. Clin. Microbiol. 39:2565-2571.) Abstract | Full Text

Apparent Gene Transfer between Bacteria and Eukaryotes

Hancock

Horizontal gene transfer is rare between bacteria and eukaryotes. Fiona S. L. Brinkman and Robert E. W. Hancock of the University of British Columbia, Vancouver, Canada, and others report what Hancock says "is the strongest case to date of probable horizontal transfer of a demonstrated virulence factor between bacteria and microbial eukaryotes." They show a large family of histidine kinases that overlaps between bacteria and fungi, and that the fungal histidine kinase gene appears to be derived from an ancestor of Streptomyces coelicolor. They also find that many family members in both kingdoms, including Pseudomonas aeruginosa GacS, are associated with virulence, and that "a distantly related histidine kinase in P. aeruginosa can control overlapping virulence properties," says Hancock. "We assume that allows different histidine kinases to promote virulence under different sets of conditions." He and Brinkman plan to investigate further cases of possible transfer of virulence between bacterial and eukaryotic pathogens.

(F. S. L. Brinkman, E. L. A. MacFarlane, P. Warrener, and R. E. W. Hancock. 2001. Evolutionary relationships among virulence-associated histidine kinases. Infect. Immun. 69:5207-5211.) Abstract | Full Text