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Published online on May 17, 2007, 10.1073/pnas.0700286104
PNAS | May 29, 2007 | vol. 104 | no. 22 | 9481-9486


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BIOLOGICAL SCIENCES / MICROBIOLOGY
Interaction between innate immune cells and a bacterial type III secretion system in mutualistic and pathogenic associations

Adam C. Silver*, Yoshitomo Kikuchi*,{dagger}, Amin A. Fadl{ddagger}, Jian Sha{ddagger}, Ashok K. Chopra{ddagger}, and Joerg Graf*,§

*Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269; {dagger}Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8566, Japan; and {ddagger}Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555

Edited by Nancy A. Moran, University of Arizona, Tucson, AZ, and approved April 9, 2007 (received for review January 11, 2007)

Animals house a community of bacterial symbionts in their digestive tracts that contribute to their well being. The medicinal leech, Hirudo verbana, has a remarkably simple gut population carrying two extracellular microbes in the crop where the ingested blood is stored. This simplicity renders it attractive for studying colonization factors. Aeromonas veronii, one of the leech symbionts, can be genetically manipulated and is a pathogen of mammals. Screening transposon mutants of A. veronii for colonization defects in the leech, we found one mutant, JG752, with a transposon insertion in an ascU homolog, encoding an essential component of type III secretion systems (T3SS). Competing JG752 against the wild type revealed that JG752 was increasingly attenuated over time (10-fold at 18 h and >10,000-fold at 96 h). This colonization defect was linked to ascU by complementing JG752 with the operon containing ascU. Fluorescence in situ hybridization analysis revealed that at 42 h 38% of JG752 cells were phagocytosed by leech macrophage-like cells compared with <0.1% of the parental strain. Using mammalian macrophages, a lactate dehydrogenase release assay revealed that cytotoxicity was significantly reduced in macrophages exposed to JG752. In a mouse septicemia model, JG752 killed only 30% of mice, whereas the parent strain killed 100%, showing the importance of T3SS for both pathogenesis and mutualism. Phagocytic immune cells are important not only in defending against pathogens but also in maintaining the mutualistic symbiont community inside the leech, demonstrating that animals use similar, conserved mechanisms to control bacterial populations, even when the outcomes differ dramatically.

Aeromonas | innate immunity | pathogenesis | symbiosis | Hirudo

Author contributions: A.C.S., Y.K., A.K.C., and J.G. designed research; A.C.S., Y.K., A.A.F., J.S., and J.G. performed research; A.C.S., Y.K., J.S., and J.G. analyzed data; and A.C.S., Y.K., J.S., A.K.C., and J.G. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. EF215451).

This article contains supporting information online at www.pnas.org/cgi/content/full/0700286104/DC1.

§To whom correspondence should be addressed. E-mail: joerg.graf{at}uconn.edu

© 2007 by The National Academy of Sciences of the USA


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 J. Bacteriol.Home page
A. C. Silver, N. M. Rabinowitz, S. Kuffer, and J. Graf
Identification of Aeromonas veronii Genes Required for Colonization of the Medicinal Leech, Hirudo verbana
J. Bacteriol., October 1, 2007; 189(19): 6763 - 6772.
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