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Journal Highlights

RNA Self-Replicating System for HCV Cell Culture Shows Promise

Lohmann (rear) and Bartenschlager

Hepatitis C virus research has been hampered by absence of an efficient cell culture system.

Previously, Ralf Bartenschlager and colleagues of Johannes Gutenberg University, Germany, had developed an RNA self-replicating system. Now, by analysis of adaptive mutations, they have been able to improve this system by several orders of magnitude. "Our main goal is to develop a system that supports replication of a full-length HCV genome," says Bartenschlager. "So far, the replicons are subgenomic and lack the complete structural genes. Therefore, we still do not have a system that supports the complete viral life cycle. However, it is now possible to introduce adaptive mutations into a cloned full-length genome. This will increase its replication to a level that hopefully it allows efficient production of virus."

(V. Lohmann, F. Korner, A. Dobierzewska, and R. Bartenschlager. 2001. Mutations in hepatitis C virus RNAs conferring cell culture adaptation. J. Virol. 75:1437-1449.) Abstract | Full Text

Dendritic Cells May Be Reservoir for Mycobacteria

Flynn and Bodnar

Like Saddam Hussein, Mycobacterium tuberculosis is persistent even against a strong immune response.

JoAnne Flynn and colleagues of the University of Pittsburgh School of Medicine, Pittsburgh, Pa., grew M. tuberculosis in dendritic cells and macrophages in vitro. Once activated, the macrophages killed the intracellular bacteria, but the dendritic cells did not, although the latter produced nitric oxide and inhibited the growth of the bacteria. "The results suggest that dendritic cells may be a reservoir for mycobacteria," says Flynn. The microbes may migrate from the lungs to the lymph nodes inside the cells, she says.

"We are comparing macrophages and dendritic cells with respect to subcellular location of the M. tuberculosis bacteria and antimicrobial effector functions," says Flynn.

(K. A. Bodnar, N. V. Serbina, and J. L. Flynn. 2001. Fate of Mycobacterium tuberculosis within murine dendritic cells. Infect. Immun. 69:800-809.) Abstract | Full Text

Adoptive Transfer of Splenocytes Vanquishes H. pylori

Helicobacter pylori infections are frustratingly persistent. But working in a new mouse model of severe gastritis in H. pylori-infected SCID mice, Kathryn A. Eaton and Megan E. Mefford of the Ohio State University, Columbus, have shown that the infection resolved following the adoptive transfer of splenocytes. "By 45 weeks after adoptive transfer, the stomachs had almost completely recovered their normal architecture," says Eaton. "We showed that the unstimulated immune response is capable of curing infection, and that even badly damaged stomachs can completely recover once the bacterial infection resolves. We are beginning to identify the cells responsible for eradicating the bacteria."

(K. A. Eaton and M. E. Mefford. 2001. Cure of Helicobacter pylori infection and resolution of gastritis by adoptive transfer of splenocytes in mice. Infect. Immun. 69:1025-1031.) Abstract | Full Text

Genomic Island Discovery in P. aeruginosa Raises New Questions

Liang

Pseudomonas aeruginosa causes a variety of serious human infections, but little work has been done to characterize genetic and clinical differences between strains.

Using strain PAO1 which was sequenced last summer as a reference, Stephen Lory of the Harvard Medical School, Boston, Mass., and others compared pathogenic isolates and found a 50-kb genomic island comprising 51 genes to be present in 85% of them but absent from PAO1. Two of the genes appear to be detoxifiers of free radicals. Analysis of flanking sequences showed that the island replaces a preexisting five-gene sequence.

"Our paper suggests a model for horizontal gene transfer where eliminating genes may be as important as acquiring of new traits," says Lory. "Interestingly, both the genomic island and the deleted region encode transcription regulators. Thus, this genetic exchange may influence large numbers of genes beyond the island, and beyond the genes it displaces."

(X. Liang, X. Q. T. Pham, M. V. Olson, and S. Lory. 2001. Identification of the genomic island present in the majority of pathogenic isolates of Pseudomonas aeruginosa. J. Bacteriol.183:1-11.) Abstract | Full Text

Molecular Ecology Elucidates Evolution of Tetracycline Resistance Genes

Aminov

Efforts to understand how antibiotic resistance spreads are hobbled by confinement of studies to cultivable bacteria. But now R. I. Aminov of the University of Illinois and colleagues have demonstrated a way to determine the presence and transmission patterns of antibiotic resistance in ecosystems. They performed a phylogenetic analysis of tetracycline resistance genes encoding ribosomal protection proteins, and then developed PCR primers enabling detection and analysis in any environmental sample.

The tetracycline resistance genes may be billions of years old, and are of monophyletic origin, contradicting the popular view that the genes were transferred from antibiotic-producing strains. "But we found that virtually identical tetracycline resistance genes circulate in the gastrointestinal tract of swine and steers, despite the different antibiotic regimen used in these animals," says Aminov. "More interestingly, the components of animal feed seemed to harbor a plethora of these genes, suggesting substantial genetic contamination in animal production."

(R. I. Aminov, N. Garrigues-Jeanjean, and R. I. Mackie. 2001. Molecular ecology of tetracycline resistance: development and validation of primers for detection of tetracycline resistance genes encoding ribosomal protection proteins. Appl. Environ. Microbiol. 67:22-32.) Abstract | Full Text

Triclosan Causes Multidrug Resistance in P. aeruginosa

Debate over Impact of Antibacterial Cleaning Agents Rejoined

Schweizer

Increasing numbers of household products, such as soaps, toys, utensils, and textiles, are impregnated with antibacterials. Herbert Schweizer of Colorado State University and others showed that when exposed to triclosan, a common antiseptic, Pseudomonas aeruginosa developed resistance to multiple antibiotics, including several key fluoroquinolones. This is worrisome because P. aeruginosa is a dangerous iatrogen, and because triclosan may cause resistance in other clinically important bacteria, says Schweizer (see Current Topics, p. 130).

Triclosan selects for the same regulatory mutations as antibiotics do," says Schweizer. The mutant P. aeruginosa over expressed a multidrug efflux pump, MexCD-OprJ. Further research showed triclosan selects for other efflux pumps, further boosting resistance. "How this relates to the real world, we don't know yet," says Schweizer. "But the concern is that antibacterial products may help create super bacteria."

(R. Chuanchuen, K. Beinlich, T. T. Hoang, A. Becher, R. R. Karkhoff-Schweizer, and H. P. Schweizer. 2001. Cross-resistance between triclosan and antibiotics in Pseudomonas aeruginosa is mediated by multidrug efflux pumps: exposure of a susceptible mutant strain to triclosan selects nfxB mutants overexpressing MexCD-OprJ. Antimicrob. Agents Chemother. 45:428-432.) Abstract | Full Text