While traditional antibiotics kill bacteria outright by interfering with processes essential for their survival, the new agent blocks production of bacterial proteins that cause the severe diarrhea associated with Vibrio cholerae infection.

"What we have done is made a custom, organism-specific antibiotic against Vibrio cholerae," said John Mekalanos, the Adele Lehman professor of microbiology and molecular genetics at HMS and the senior author on a report of the work appearing in the online edition of Science.

Using a high-throughput screen of 50,000 small molecule candidate compounds, Mekalanos and lead author Deborah Hung identified several that turned off the expression of virulence proteins, factors that help the bacteria invade its human host and cause disease. They then showed that the most promising compound prevented cholera bacteria from setting up an infection when introduced into the digestive tract of mice.

Since most disease-causing organisms use elaborate virulence factors such as toxins to do their damage, the new approach should be widely applicable. "There is no reason our results cannot be replicated for a number of other important pathogens," Mekalanos said.

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"For each major conduct symptom in a child's life, the age of first drink decreased by about three months," added Kuperman, who also is director of the child psychiatry division in Children's Hospital of Iowa at UI Hospitals and Clinics.

Kuperman said some previous studies reported that a family history of alcoholism or antisocial personality disorder relates to an earlier age of first drink. However, he noted, those studies did not take into account the additional negative behaviors and conditions included in the current study.

"This study helps put things in perspective. It is not just the age of first drink that relates to negative outcomes. There are often bad things happening to these children and the age of first drink represents just one of them and is not the most important one," Kuperman said.

Kuperman said the team will continue to study what factors, including age of first drink, are important in predicting negative outcomes for youth.

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