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Infection and Immunity, March 2009, p. 1022-1030, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01064-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Emerging Human Pathogen Photorhabdus asymbiotica Is a Facultative Intracellular Bacterium and Induces Apoptosis of Macrophage-Like Cells{triangledown}

S. C. P. Costa,1,2,3 P. A. Girard,1,2 M. Brehélin,1,2 and R. Zumbihl1,2*

Université Montpellier II, UMR1133 Laboratoire EMIP, F-34095 Montpellier, France,1 INRA, UMR1133 Laboratoire EMIP, F-34095 Montpellier, France,2 Departamento de Biologia, Universidade dos Acores, Rua Mãe de Deus, Ponta Delgada Açores, Portugal3

Received 27 August 2008/ Returned for modification 8 October 2008/ Accepted 4 December 2008

Photorhabdus species are gram-negative entomopathogenic bacteria of the family Enterobacteriaceae. Among the different members of the genus, one species, Photorhabdus asymbiotica, is a pathogen of both insects and humans. The pathogenicity mechanisms of this bacterium are unknown. Here we show that P. asymbiotica is a facultative intracellular pathogen that is able to replicate inside human macrophage-like cells. Furthermore, P. asymbiotica was shown for the first time in an intracellular location after insect infection. We also demonstrated that among Australian and American clinical isolates, only the Australian strains were able to invade nonphagocytic human cells. In cell culture infection experiments, Australian clinical isolates as well as cell-free bacterial culture supernatant induced strong apoptosis of a macrophage cell line at 6 h postinfection. American isolates also induced cellular death, but much later than that induced by Australian ones. Mammalian cultured cells analyzed for key features of apoptosis displayed apoptotic nuclear morphology, activation of the initiator caspases 8 and 9 and the executioner caspases 3 and 7, and poly(ADP-ribose) polymerase proteolysis, suggesting activation of both the intrinsic and extrinsic apoptotic pathways.

* Corresponding author. Mailing address: Université Montpellier II, UMR1133 Laboratoire EMIP, F-34095 Montpellier, France. Phone: (33) 04 67 14 46 72. Fax: (33) 04 67 14 46 79. E-mail: zumbihl{at}univ-montp2.fr

{triangledown} Published ahead of print on 15 December 2008.

Editor: A. J. Bäumler

Infection and Immunity, March 2009, p. 1022-1030, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01064-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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