Hunting Down a Killer-Bacterium's Infectious Protein

	The Cornell-Oswaldo Cruz Foundation/Brazilian Ministry of Health community site where Dr. Ko and his team are researching rat-borne leptospirosis among urban slum residents.

A marksman needs certain key conditions for success – one essential factor is having a clear target to shoot at. Just like an archer aiming for a bull's-eye, Weill Cornell Medical College physician-scientists have targeted a protein they believe is responsible for leptospirosis, a bacterial disease transmitted from animals to humans, which infects a half-million people and leads to the death of up to 100,000, annually.

Researchers located a protein on the surface of the bacterium, Leptospira interrogans – responsible for causing leptospirosis. Doing so may help scientists create a vaccine to one-day shoot down the sickness-causing germ.

"The disease is a major public health problem in urban slums of developing countries, such as Brazil," says Dr. Albert Ko, contributing researcher in the study and physician-scientist from the Division of International Medicine and Infectious Disease at Weill Cornell Medical College. Dr. Ko is stationed at Oswaldo Cruz Foundation/Brazilian Ministry of Health in the city of Salvador, Brazil, as coordinator of a collaborative research and training program of infectious diseases and urban poverty.

Findings published in the July edition of the Public Library of Science: Pathogens (PLoS) show that the bacterium is rendered non-functional and unable to produce disease in guinea pig models, when a gene producing a protein called Loa22 is disrupted. Before these findings, the active agent causing the disease was completely unknown.

	An electron micrograph of the pathogen, Leptospira interrogans, which is the cause of leptospirosis. The strain shown in the photo was obtained from a patient with severe leptospirosis in Salvador.

The study was the first to identify a virulence factor in the Leptospira bacteria. When the gene was reintroduced, the bacteria-strains regained their virulence and ability to cause leptospirosis and death in guinea pigs.

In humans, leptospirosis is characterized by high fever, severe headache, chills, muscle aches, vomiting, and may lead to jaundice (yellow skin and eyes), red eyes, abdominal pain, diarrhea or a rash. If left untreated, a human patient might develop kidney damage, meningitis (inflammation of the membrane around the brain and spinal cord), liver failure and respiratory distress, according to the Centers for Disease Control. Furthermore, infection with the Leptospira bacteria can cause a severe pulmonary hemorrhage, which is associated with death in more than 50 percent of the cases with this syndrome.

The only way to diagnose leptospirosis is through blood and urine testing, because symptoms can easily be misdiagnosed for other illnesses. Treatment includes a course of oral antibiotics, like penicillin, early in the disease. But, if the symptoms are severe, intravenous antibiotics are necessary.

People who work with, or who are around animals like cattle, pigs, horses, dogs, rodents and wild animals should take extra caution. Leptospira interrogans is found in the urine of infected animals.

The team from the Cornell Global Infectious Disease Training Program at the Oswaldo Cruz Foundation, (left to right) Flavia McBride, Albert Ko and Claudio Figueira.

Humans might become infected through contact with water, food or soil containing urine from these infected animals. This may happen by swallowing contaminated food or water or through skin contact, especially broken skin, or through the eyes or nostrils. It is not spread from one person to another.

In cities, in developing countries, like Brazil, large epidemics of rat-borne leptospirosis occur each year during the rainy season, explains Dr. Ko.

Other names for leptospirosis are also Weil's disease, canicola fever, hemorrhagic jaundice, infectious jaundice, mud fever, spirochetal jaundice, swamp fever, swineherd's disease, caver's flu or sewerman's flu.

The study that led to the identification of the first virulence factor in Leptospira was done in collaboration with Dr. Mathieu Picardeau's group at Institut Pasteur, Paris. The lead author of the article, Paula Ristow, is a trainee in the Weill Medical College Global Infectious Disease Training Program coordinated by Dr. Ko in Brazil, as are two other authors, Flávia McBride and Claudio Figueira.

For media inquiries please contact Andrew Klein at 212-821-0560 or ank2017@med.cornell.edu