Journal Highlights


N. gonorrhoeae: Change of Coat for Acid Conditions

As many as 3 million cases of gonorrhea may occur annually in the United States, according to the American Medical Association. Several observations have supported the hypothesis that pH influences pathogenesis of Neisseria gonorrhoeae. For example, intact gonococci and purified gonococcal pili adhere most strongly to vaginal epithelial cells at pH 4.5. Now, for what may be the first time, researchers have evidence that the surface of N. gonorrhoeae changes according to pH, which may range from 4.1 to 8.4 depending on the urogenital location and the sex of the host.

"We found that with acid stress, N. gonorrhoeae upregulates the synthesis of several outer membrane proteins, including the conserved stress protein hsp6O," says Robin K. Pettit, of Western Oregon State College. "If these outer membrane proteins are expressed in acidic urogenital sites in vivo, they need to be evaluated as potential chemotherapeutic and vaccine targets."

(R.K. Pettit, M. J. Filiatrault, and E. S. Martin. 1996. Alteration of gonococcal protein expression in acidic culture. Infect. Immun. 64:1039-1042.)


Worms Influence Fate of Genetically Engineered Soil Microbes

The release of genetically engineered microorganisms into the environment raises concerns about environmental impact.

Michael J. Sadowsky of the University of Minnesota and his colleagues have developed a model system to assess the influence of earthworm activity on transfer of a plasmid from a donor bacterium to indigenous soil microorganisms. The researchers found that earthworms in different ecological groups differentially affect survival, distribution, and gene transfer of inoculated bacteria in the soil, such as increasing diversity of bacterial transconjugants and acting as vectors for dispersal of donor and transconjugant bacteria.

"In future studies we will determine whether transconjugant indigenous soil bacteria acquired new genes within earthworm cocoons and intestinal tracts and whether transconjugant soil bacteria have a selective advantage in colonizing specific ecosystems," says Sadowsky.

(L.L. Daane, J. A. E. Molina, E. C. Berry, and M. J. Sadowsky. 1996. Influence of earthworm activity on gene transfer from Pseudomonas fluorescens to indigenous soil bacteria. Appl. Environ. Microbiol. 62:515-521.)


Aliphatic Epoxides Detoxified by Novel Route

Aliphatic epoxides are highly reactive, toxic molecules that have mutagenic and, in some instances, carcinogenic properties. In recent years, researchers have pursued biological strategies to degrade and detoxify these molecules. Scott A. Ensign and Jeffrey R. Allen of Utah State University, Logan, have revealed a new pathway whereby CO2 added to aliphatic epoxicies to produce ß-keto acids, which are central metabolites that can be beneficially metabolized and completely mineralized to produce CO2 and water.

"A major emphasis of our current research is to purify to homogeneity and biochemically characterize the epoxide carboxylase from Xanthobacter strain Py2," says Ensign. "Its in vitro requirements in cell extracts are intriguing: the enzyme requires both a dithiol and NAD+ in order to function. In contrast, ATP, a required cofactor for many carboxylases, is apparently not required by the enzyme."

(J.R. Allen and S. A. Ensign. 1996. Carboxylation of epoxides to ß-keto acids in cell extracts of Xanthobacter strain Py2. J. Bacteriol. 178:1469-1472.)


HCMV Blasts Cells with Mere Entry

Human cytomegalovirus (HCMV) is one of the principal causes of congenital malformation and a major cause of disease and death in transplant patients. It triggers an acute immunosuppressed state.

Oddly enough, even during full-blown disease, HCMV infects less than 0.1% of cells that are involved in immune functions. This raised the question of how this virus can globally modify the immune system in the absence of replication in immunocompetent cells.

Now Susan Michelson of the Institut Pasteur and her colleagues have shown that the mere entry of even thenonreplicating HCMV into a cell can modify host cell functions within 10 min and prior to any expression of the viral genome. Such modifications include hypophosphorylation of newly infected cell proteins. "We are therefore currently trying to identify incoming viral proteins which are involved in hyperimmediate modifications of the host cell," says Michelson, which may "help in the development of new antiviral drugs."

(S.Michelson, P. Turowski, L. Picard, J. Goris, M. P. Landini, A. Topilko, B. Hemmings, C. Bessia, A. Garcia, and J. L. Virelizier. 1996. Human cytomegalovirus carries serine/threonine protein phosphatases PP1 and a host-cell derived PP2A. J. Virol. 70:1415-1423.)


Histone H4 Maintains Genome Integrity

Histones are essential for the assembly and function of eukaryotic chromosomes. Now M. Mitchell Smith and his colleagues at the University of Virginia Cancer Center have discovered a novel function for histone H4: maintenance of genome integrity. This group has identified the first temperature-sensitive lethal H4 mutant, in Saccharomyces cerevisiae, which is defective in mitotic chromosome transmission and nuclear division.

The work also shows that H4 interacts genetically with Cse4p, a unique histone H3 variant, and that this interaction is required for proper mitotic chromosome transmission, says Smith, who plans relevant genetic experiments.

Similarity between Cse4p and CENP-A, a mammalian kinetochore antigen, suggests that the specialized H4-Cse4p nucleosomes are part of the yeast kinetochore, "a view that has already made it into two recent review articles-without a shred of direct evidence," says Smith, who plans to test the hypothesis directly.

(M.M. Smith, P. Yang, M. S. Santisteban, P. W. Boone, A.T. Goldstein, and P. C. Megee. 1996. A novel histone H4 mutant defective in nuclear division and mitotic chromosome transmission. Mol. Cell. Biol. 16:1017-1026.)


Novel Oxazolidinones Squash Resistant Gram-Positive Organisms

Gram-positive bacteria cause the most prevalent and serious bacterial infections. Resistance among important gram-positive cocci to commonly used antimicrobial agents has climbed at an alarming rate. Vancomycin, long active against all gram-positive cocci, has lost effectiveness against enterococci, and penicillin resistance among pneumococci now exceeds 20% in the United States.

Now Ronald N. Jones and colleagues at the University of Iowa College of Medicine have demonstrated that two new Upjohn oxazolidinone antibiotics have universal activity in vitro against gram-positive bacteria, including vancomycin-resistant enterococci, methicillin-resistant staphylococci, and multi-resistant pneumococci. Preliminary oral and parenteral data are promising as well, says Jones.

(R.N. Jones, D. M. Johnson, and M. E. Erwin. 1996. In vitro antimicrobial activities and spectra of U-100592 and U-100766, two novel fluorinated oxazolidinones. Antimicrob. Agents Chemother. 40:720-726.)

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