Researchers Work to Develop Avian Pathogenic <I>E. coli</I> Vaccine

Biodesign Institute at Arizona State University associate research scientist Melha Mellata is leading a USDA funded project to develop a vaccine against a leading poultry disease called avian pathogenic E. coli (APEC).

APEC is part of a large, diverse group of microbes called extra-intestinal pathogenic E. coli (ExPEC). They cause a number of complex brain, lung and urinary tract diseases in human, animals and birds. There is also considerable concern in the scientific community that APEC strains are becoming an emergent food pathogen. The poultry products are a suspected source of a suite of ExPEC infections, including those causing human disease.

The United States is the leading poultry industry in the world at an annual value of more than $50 billion, and E. coli infections are a big threat, causing millions in losses for the industry. According to the USDA, the two most common types of poultry infections are from the bacteria E. coli and Salmonella.

Antibiotics have long been the first line of defense to prevent APEC, but have lost their potency, as the bacteria have grown increasingly resistant to treatment. How these microbes cause disease is poorly understood. Mellata and colleagues in the institute's Center for Infectious Diseases and Vaccinology, led by Roy Curtiss, have been hard at work to understand the molecular tricks these bacteria use to evade a host's immune system.

Now, in a paper published in the journal PLoS One, Mellata's team has analyzed the DNA sequence of a critical genetic element of APEC that contains several genes responsible for triggering its harmful effects. In addition, by comparing these genes to a collection of human ExPEC strains, they have shown that human and avian E. coli can carry the same disease-causing elements, which may increase the human risk of infection from poultry.

"The best way to prevent this infection is to develop a vaccine," said Mellata. "Our idea is to ultimately protect both poultry and humans by finding a group of genes common against all extra-intestinal E. coli." With this new knowledge of APEC, the group hopes to pursue the development of several new vaccine candidates.

Their latest research results help narrow the genetic search for the cause of APEC infections. Previously, she had shown that a circular, 100,000 base pair long DNA segment, called a plasmid, was responsible for causing disease. Without the plasmid, APEC becomes docile, losing its disease-causing strength.

Plasmids, in an evolutionary game of high-stakes poker, are swapped freely among bacteria in order to gain the upper hand — or in the case of pathogenic E. coli, to outwit its competitors by colonizing animals and causing disease. Over time, each plasmid becomes a patchwork quilt of DNA information, containing DNA parts exchanged among billions of bacterial encounters.

Her team took advantage of the latest advances in DNA sequencing to analyze the complete 103,275 DNA chemical letters that make up the plasmid, called pAPEC-1.

The multidisciplinary effort involved expertise from several ASU researchers, including Jeff Touchman, a School of Life Science Professor specializing in bioinformatics. It also utilized MEGA4, a software program developed by the Biodesign colleague Sudhir Kumar's lab that is used by more than 50,000 scientists worldwide to trace back and compare the evolutionary history of any DNA segment.

"DNA sequencing and bioinformatics analysis are very powerful tools that contribute in fully understanding the virulence of APEC, and provide new avenues of research," said Mellata.