On Aug. 19, in rural Colorado, a 31-year-old man rescued hisfriend's sick cat from a trailer crawl space. One week later, theGood Samaritan was dead of pneumonic plague -- the firstplague fatality in the U.S. since 1987, the Centers for DiseaseControl (CDC) reported.

Thomas Quan, of the CDC's Division of Vector-Borne Diseases inFt. Collins, Colo., told BioWorld that the victim was notscratched or bitten by the animal, but did have "severalminutes of face-to-face breathing contact with the cat," whichdied that same day.

The cat presumably harbored fleas from a chipmunk, whosedead body was later found to be laden with Yersinia pestis, thegram-negative bacterium that carries plague. The cat's breathwas freighted with highly contagious aerosol Y. pestis droplets.

Quan co-authored a paper in Friday's Science titled "A SurfaceProtease and the Invasive Character of Plague." It reportsresearch by molecular biologist Jon D. Goguen and his associatesat the University of Massachusetts Medical School that revealsthe role of a gene called pla in the Y. pestis genome.

Pla resides on a 9.5-kilobase plasmid (expression vector) in thebacterium. It encodes a protein-cleaving enzyme called Pla onthe bacterial cell surface. In mice, the Pla protease increasedthe lethal dose of Y. pestis 1 million-fold.

To achieve this escalation of virulence, Pla acts exactly like atissue plasminogen activator, such as human urokinase orrecombinant t-PA. It dissolves the mesh of fibrin that the bodyweaves at the pathogen's site of entry -- usually an infectedflea bite. This entangling fibrin clot entraps the bacteria toprevent them from penetrating internal organs. Clot-lysing Plareopens their lethal pathway.

To prove this effect, Goguen's team created Y. pestis mutantslacking the pla gene, and injected them under the skin of mice.Besides producing a local infection, these mutants "greatlyreduced ability to establish infection in liver and spleen, andare essentially a virulent by this route." Their experiment wenton to show that "nonetheless, they (the pla-minus mutants)remain highly virulent if delivered intravenously," thusevading the fibrin barrier.

A second mechanism by which Pla may frustrate the body'sdefenses against Y. pestis is by short-circuiting the alternativecomplement pathway, which summons bacteria-scavengingpolymorphic neutrophils to the scene of entry, the flea-bite.

In bygone centuries, pandemics of plague brought down wholepopulations in Europe and Asia. In the U.S., it is endemic amongrodents and their fleas in the Rocky Mountain and Pacificstates, where so far this year, 11 people contracted plague, thesame as so far last year. CDC warned in its Oct. 23 report that"increased risk for human cases will persist into 1993 andbeyond."

Thanks to antibiotics and early diagnosis, this risk is no longera likely death sentence, but the plague paper in last week'sScience may pay off in future management of less-virulentgram-negative infections. Goguen's group found largelyhomologous gene sequences to Y. pestis pla in Escherichia coli,salmonella typhimurium and S. typhi.

"The role of Pla in plague," the researchers suggest, "impliesthat this class of proteases may contribute, in a more subtleway, to the capacity of less virulent species to producedisseminated infection, a major source of mortality forimmunocompromised patients."

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.

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