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Science 17 October 2003:
Vol. 302. no. 5644, pp. 462 - 464
DOI: 10.1126/science.1088170
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Reports

Listeria Intracellular Growth and Virulence Require Host-Derived Lipoic Acid

Mary O'Riordan,1* Marlena A. Moors,2 Daniel A. Portnoy1,3

Listeria monocytogenes is a Gram-positive intracytosolic pathogen that causes severe disease in pregnant and immunocompromised individuals. We found that L. monocytogenes lacking the lipoate protein ligase LplA1 was defective for growth specifically in the host cytosol and was less virulent in animals by a factor of 300. A major target for LplA1, the E2 subunit of pyruvate dehydrogenase (PDH), lacked a critical lipoyl modification when the {Delta}lplA1 strain was grown intracellularly, which suggests that abortive growth was due to loss of PDH function. Thus, the use of host-derived lipoic acid may be a critical process for in vivo replication of bacterial pathogens.

1 Department of Molecular and Cell Biology, School of Public Health, University of California, Berkeley, CA 94720–3202, USA.
2 Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
3 Division of Infectious Disease, School of Public Health, University of California, Berkeley, CA 94720–3202, USA.

* To whom correspondence should be addressed. Present address: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109–0620, USA. E-mail: oriordan{at}umich.edu

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