Resistance of Yersinia pestis to Complement-Dependent Killing is Mediated by the Ail Outer Membrane Protein

Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710; Department of Microbiology and Immunology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202; Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, NIH, NIAID, Hamilton, MT 59840; Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden

^* To whom correspondence should be addressed. Email: gplano{at}med.miami.edu.

	Abstract

Y. pestis, the causative agent of plague, must survive in blood in order to cause disease and to be transmitted from host-to-host by the flea. Members of the Ail/Lom family of outer membrane proteins provide protection from complement-dependent killing for a number of pathogenic bacteria. The Y. pestis KIM genome is predicted to encode four Ail/Lom family proteins. Y. pestis mutants specifically deficient in expression of each of these proteins were constructed using lambda Red-mediated recombination. The Ail outer membrane protein was essential for Y. pestis to resist complement-mediated killing at 26°C and 37°C. Ail was expressed at high levels at both 26°C and 37°C, but not at 6°C. Expression of Ail in E. coli provided protection from the bacteriocidal activity of complement. High-level expression of the three other Y. pestis Ail/Lom family proteins (y1682, y2034 and y2446) provided no protection against complement-mediated bacterial killing. A Y. pestis ail deletion mutant was rapidly killed by sera obtained from all mammals tested except mouse serum. The role of Ail in infections of mice, C. elegans and fleas was investigated.