By David N. Leff

Editor s note: Science Scan is a roundup of recently published biotechnology-relevant research.

It took 55 co-authors from a dozen institutes in France, Germany and Spain to sequence the genome of Listeria monocytogenes, one of the nastiest bacteria that infect humans. In fact, the collaborators got two for the price of one: L. monocytogenes has a nonidentical twin, aptly named L. innocua, because it s harmless to people.

A paper in Science dated Oct. 26, 2001, reports on Comparative genomics of Listeria species. Its senior author is cell microbiologist Pascale Cossart, who heads the Bacterial Cell Interaction Unit at the Pasteur Institute in Paris. There is a degree of poetic logic in this Listeria connection, as the bacterium and its infection Listeriosis are named for Joseph (Lord) Lister (1827-1912), the British pioneer of antisepsis, whose early mentor was the French founder of bacteriology, Louis Pasteur (1822-1895).

L. monocytogenes tips the scales at 2,944,528 base pairs in a circular chromosome; L. innocua is almost identical at 3,011,209 bp. Listeria monocytogenes, the Science paper leads off, is a food-borne pathogen with a high mortality rate that has also emerged as a paradigm for intracellular parasitism. It adds: The presence of 270 L. monocytogenes and 149 L. innocua strain-specific genes (clustered in 100 and 63 islets, respectively) suggests that virulence in Listeria results from multiple gene acquisition and deletion events. (For how this virulence devastates the human gut and brain, see BioWorld Today, June 4, 2001, p. 1.)

The co-authors identified 2,853 protein-coding genes in the L. monocytogenes chromosome and 2,973 in that of L. innocua, which also contains an 81,905-bp plasmid encoding heavy metal resistance. Encoded proteins, the paper reported, revealed a striking similarity to those of the soil bacterium Bacillus subtilis. No function could be predicted for 35.3 percent of L. monocytogenes genes and 37 percent of L. innocua genes, a proportion similar to that found in other sequenced bacterial genomes.

Analysis of the many surface proteins and adaptation systems, the paper concluded, opens new avenues for postgenomic analysis of the lifestyles of L. monocytogenes in the environment and the infected host.

Yalies Do Undoable: Microchip Proteome Analysis Of Yeast Protein Complement

A single baker s yeast cell (Saccharomyces cerevisiae) contains some 6,200 genes, each of which encodes a protein. These interact to develop and sustain life. Studying so many proteins simultaneously on a near-total scale had never been done, and seemed to many scientists scarcely doable. Now Michael Snyder, the chair of molecular, cellular and developmental biology at Yale University in New Haven, Conn., reports accomplishing this impossible dream. Snyder is senior author of a paper in Science dated Sept. 14, 2001, but originally published electronically on July 26, 2001. It s titled: Global analysis of protein activities using proteome chips.

The Yale team cloned and purified 5,800 of yeast s 6,200 proteins and spotted them within a postage stamp-size space on a nickel-coated glass microscope slide. This microarray chip revealed the interaction of the proteins with other proteins tagged to glow when one protein bound to another. This initial proteomic analysis disclosed many previously unknown protein functions.

Snyder is now at work moving up from S. cerevisiae to H. sapiens designing a human protein chip. Humans, he suggests, are likely to have proteins in their genomes numbering in the hundreds of thousands. Focusing on proteomic analysis of a single protein expressed by each of the few thousand known genes in the human genome, he believes, may lead to rapid advances in the understanding of human biology.

Snyder pointed out, Diseases can arise when proteins do not interact properly. This chip technology allows us to get at the function of many of the different proteins far faster than current methods. It could speed the development of new diagnostic methods, advancements in drug discovery, and improvements in therapies for diseases.

Tropical Liver Flukes Tune Their On-Or-Off Reproduction To CD4 T Lymphocytes

When the AIDS virus (HIV-1) takes aim at infecting its human host, the bull s eye in the viral cross-hairs is the key immune system, carrying its CD4-positive (CD4+) T lymphocyte as a flag. Yet paradoxically a population of similar CD4+ cells can make life easier for people afflicted with schistosomiasis.

This tropical disease, caused by infection with a worm-like helminth liver fluke (Schistoma mansoni), is endemic in Africa, parts of the Middle East and West Indies, South America and certain Caribbean islands. That water-borne parasite doesn t worm its way into its victim s liver all by itself. Most people in tropical climes go barefoot, so they pick up a freshwater snail, of the genus Biomphalaria, which transmits the S. mansoni pathogen into their blood, en route to the liver where it will live. A paper in Science dated Nov. 9, 2001, sums up the unfolding story. Its title: Modulation of blood fluke development in the liver by hepatic CD4+ lymphocytes. The authors are immunologists and microbiologists at the University of California at San Francisco.

They report that immune system T lymphocytes bearing the CD4+ badge may emit cellular signals that direct the fluke s development. These commands monitor changes in the parasite s environment so they may adjust their own life cycles accordingly. The co-authors performed experiments on knockout mice lacking the CD4+ T lymphocytes, and discovered that blood fluke egg production was both delayed and reduced. They suggest that the flukes interpreted the consequent missing signals as spelling trouble for their mammalian host, so they turned off their own reproduction until better times return. Parasites can survive for decades within their infected hosts, the Science paper points out.

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