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Cholera primed by gut transit
Gastroenterology News Anil K. Rustgi, Section Editor
Cholera Primed By Gut Transit
T
and microbiology and immunology at Stanford University, turned to transcriptional profiling. Probing for differences in gene expression, they exposed a microarray containing segments of 3357 Vibrio genes to Vibrio RNA isolated from fresh stools and from laboratory strains of the bacteria. In the stool-derived sample, the microarray probe revealed greater activity in 44 genes and less activity in 193 genes than in other genes studied. Further study revealed silencing of several genes responsible for chemotaxis, which meant the bacteria were “swimming blindly” via their flagella when excreted and not heading toward or away from chemical targets. Camilli says this finding was of great interest because his laboratory had previously shown that mutant strains of the microbe that were motile and nondirectional were hyperinfectious and that they colonized throughout the intestinal tract, rather than mainly in the lower small intestine. On seeing similar data in the stoolderived Vibrio, “we were excited because we thought here’s a potential explanation for why they are hyperinfectious.” Camilli says the findings of
enhanced infectivity and maintenance of that state over a period of time in pond water suggest this “may be an important factor in rapid epidemic spread” in humans. In addition, he sees the study as having implications for vaccine development. Perhaps cholera and other enteric vaccines “should be based on the natural transmissible state of the bacteria.” Agreement on this comes from coauthor Dr. Firdausi Qadri, immunologist and senior scientist in the laboratory sciences division of the International Center for Diarrheal Disease and Research (ICDDR) in Dhaka, Bangladesh. Out of roughly 100,000 people seeking treatment each year at the ICDDR hospital, about 15,000 to 20,000 are infected with V. cholerae. “Our recent study of the host-induced epidemic spread of V. cholerae shows us that the concept of the design of vaccines may need to be revisited,” she states. For more about ICDDR, Bangladesh, go to www.icddrb.org
ransit through the gut greatly enhances infectivity of Vibrio cholerae, the microorganism responsible for the deadly diarrheal disease, according to a report in the June 6, 2002 issue of Nature. Initial support for this hypothesis arose from experiments in Bangladesh involving mice co-inoculated with laboratory-grown V. cholerae and cholera bacteria derived from fresh human stools. The stool-derived bacteria “outcompeted the laboratory-grown strain by quite a large degree,” says Dr. Andrew Camilli, Assistant Professor of Molecular biology and Microbiology at Tufts University School of Medicine, a coauthor of the report and whose graduate students conducted the animal experiments. Indeed, Vibrio from fresh cholera stools were “hyperinfectious,” calculated at up to 700 times more so than the laboratorygrown strain. The Tufts researchers then diluted cholera stool-derived bacteria in pond water from 2 sources in BangAGA Advocacy Helps Prompt ladesh. After 5 hours incubation, the IBD Act experiments in mice were repeated with similar results. NorThe AGA played a leading mally, people do not come advocacy role in the May 23 into contact with fresh introduction of the Inflamcholera stool. However, matory Bowel Disease Act Vibrio does get into the by Senate Majority Whip water supply via rivers and Harry Reid, D-NV. If ponds, Camilli explains. adopted, the Act, S. 2563, “Our hypothesis based on would authorize $75 million that data is that Vibrio is in in fiscal year 2003 and $100 a heightened state of transmillion in FY 2004 for supmissibility in the natural sitport of inflammatory bowel uation when there is epidisease (IBD) research at the demic spread. And that’s a NIDDK. new discovery.” “This is an exceptionally To understand the eximportant development for creted microbe’s heightgastroenterology and for gasened infectivity compared with laboratory-grown Vibrio, An electron micrograph showing a microcolony of Vibrio cholerae troenterology research,” said attached to crypt cells in the mouse small intestine. Photograph Dr. Mark Donowitz, chair of Camilli and Dr. Gary School- provided courtesy of Michael Angelichio and Andrew Camilli. AGA’s Public Policy Commitnik, professorof medicine
GASTROENTEROLOGY 2002;123:403– 404
Cholera Primed By Gut Transit
T
and microbiology and immunology at Stanford University, turned to transcriptional profiling. Probing for differences in gene expression, they exposed a microarray containing segments of 3357 Vibrio genes to Vibrio RNA isolated from fresh stools and from laboratory strains of the bacteria. In the stool-derived sample, the microarray probe revealed greater activity in 44 genes and less activity in 193 genes than in other genes studied. Further study revealed silencing of several genes responsible for chemotaxis, which meant the bacteria were “swimming blindly” via their flagella when excreted and not heading toward or away from chemical targets. Camilli says this finding was of great interest because his laboratory had previously shown that mutant strains of the microbe that were motile and nondirectional were hyperinfectious and that they colonized throughout the intestinal tract, rather than mainly in the lower small intestine. On seeing similar data in the stoolderived Vibrio, “we were excited because we thought here’s a potential explanation for why they are hyperinfectious.” Camilli says the findings of
enhanced infectivity and maintenance of that state over a period of time in pond water suggest this “may be an important factor in rapid epidemic spread” in humans. In addition, he sees the study as having implications for vaccine development. Perhaps cholera and other enteric vaccines “should be based on the natural transmissible state of the bacteria.” Agreement on this comes from coauthor Dr. Firdausi Qadri, immunologist and senior scientist in the laboratory sciences division of the International Center for Diarrheal Disease and Research (ICDDR) in Dhaka, Bangladesh. Out of roughly 100,000 people seeking treatment each year at the ICDDR hospital, about 15,000 to 20,000 are infected with V. cholerae. “Our recent study of the host-induced epidemic spread of V. cholerae shows us that the concept of the design of vaccines may need to be revisited,” she states. For more about ICDDR, Bangladesh, go to www.icddrb.org
ransit through the gut greatly enhances infectivity of Vibrio cholerae, the microorganism responsible for the deadly diarrheal disease, according to a report in the June 6, 2002 issue of Nature. Initial support for this hypothesis arose from experiments in Bangladesh involving mice co-inoculated with laboratory-grown V. cholerae and cholera bacteria derived from fresh human stools. The stool-derived bacteria “outcompeted the laboratory-grown strain by quite a large degree,” says Dr. Andrew Camilli, Assistant Professor of Molecular biology and Microbiology at Tufts University School of Medicine, a coauthor of the report and whose graduate students conducted the animal experiments. Indeed, Vibrio from fresh cholera stools were “hyperinfectious,” calculated at up to 700 times more so than the laboratorygrown strain. The Tufts researchers then diluted cholera stool-derived bacteria in pond water from 2 sources in BangAGA Advocacy Helps Prompt ladesh. After 5 hours incubation, the IBD Act experiments in mice were repeated with similar results. NorThe AGA played a leading mally, people do not come advocacy role in the May 23 into contact with fresh introduction of the Inflamcholera stool. However, matory Bowel Disease Act Vibrio does get into the by Senate Majority Whip water supply via rivers and Harry Reid, D-NV. If ponds, Camilli explains. adopted, the Act, S. 2563, “Our hypothesis based on would authorize $75 million that data is that Vibrio is in in fiscal year 2003 and $100 a heightened state of transmillion in FY 2004 for supmissibility in the natural sitport of inflammatory bowel uation when there is epidisease (IBD) research at the demic spread. And that’s a NIDDK. new discovery.” “This is an exceptionally To understand the eximportant development for creted microbe’s heightgastroenterology and for gasened infectivity compared with laboratory-grown Vibrio, An electron micrograph showing a microcolony of Vibrio cholerae troenterology research,” said attached to crypt cells in the mouse small intestine. Photograph Dr. Mark Donowitz, chair of Camilli and Dr. Gary School- provided courtesy of Michael Angelichio and Andrew Camilli. AGA’s Public Policy Commitnik, professorof medicine
GASTROENTEROLOGY 2002;123:403– 404