Photorhabdus asymbiotica

From insects to human hosts: Identification of major genomic differences between entomopathogenic strains of
Photorhabdus and the emerging human pathogen Photorhabdus asymbiotica

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Slim Tounsia, Mark Blightb, Samir Jaouaa and Andréa de Lima Pimentac, ,
aLaboratoire des Biopesticides, Centre de Biotechnologie de Sfax, B.P.”K”, 3038 Sfax, Tunisie
bCentre de Génétique Moléculaire, Bât. 26, CNRS, F-91198 Gif-sur-Yvette, France
cUniversité de Cergy-Pontoise, Dept. Biologie, Lab. ERRMECe, F-95302 Cergy-Pontoise Cedex, France

Received 14 November 2005;  revised 10 March 2006;  accepted 8 June 2006.  Available online 6 October 2006.

Pathogenic bacteria of the genus Photorhabdus are naturally found in symbiotic association with soil
entomopathogenic nematodes, and are of increasing economic interest in view of their potential for the development of
novel biopesticides. This bipartite natural system is currently used for the biological control of crop pests in several
countries. However, an increasing number of Photorhabdus strains have recently been isolated from human clinical
specimens in both the United States and Australia, associated with locally invasive soft tissue infections and
disseminated bacteraemia. In view of their growing use in biological control, which increases the potential rate of
exposure of humans to these pathogens, we decided to undertake a comparative study of the genomic differences
between insect and human pathogenic strains of Photorhabdus, in an attempt to understand the genetic mechanisms
involved in the apparent change of host specificity, presumably responsible for their recently acquired capacity to
infect humans. The data presented here demonstrates that major genomic differences exist between strains of
Photorhabdus exhibiting virulence against insects or humans. Several individual genes, coding for virulence factors,
were isolated and shown to be specific to the Photorhabdus asymbiotica human pathogens. One of these genes,
sopB, encoding a host cell invasion factor translocated via the type III secretion system, has been cloned and the
comparison of its genomic context in different pathogens strongly indicates that horizontal gene transfer is implicated
in the acquisition of these virulence factors specific to the human pathogens. The precise role of this and other
virulence factors identified here in the pathogenicity of P. asymbiotica towards humans is currently under investigation

The three currently recognised Photorhabdus species are bioluminescent bacteria that are pathogenic to insects. P.
luminescens and P. temperata form a symbiotic relationship with nematodes that infect insects. P. asymbiotica, on the
other hand, has only been isolated from human clinical specimens from the USA and Australia. The bacterium has
been associated with
locally invasive soft tissue and disseminated bacteraemic infections. An invertebrate vector
for P. asymbiotica has not yet been identified.

Most newly recognized human pathogens are zoonotic (i.e., able to infect nonhuman animal species) (1). Although it is
well established that vertebrates are associated with emerging human infectious disease, the role of invertebrates,
which constitute >95% of known animal species, has received far less attention.

The genomics era, however, has resulted in a dawning recognition of the importance of invertebrates in the
emergence of human infection (2). For example, the virulent insect pathogen Bacillus thuringiensis is genetically
closely related to the human pathogen Bacillus anthracis, the cause of anthrax (3). Yersinia pestis, the cause of
plague, contains insecticidal toxins, which may have been laterally transferred from the insect pathogen Photorhabdus
luminescens (4).

Photorhabdus organisms are γ-proteobacteria that display the curious property of bioluminescence (they glow in the
dark); 3 species are currently recognized: P. asymbiotica, P. luminescens, and P. temperata (5). The latter 2 species
have been intensively studied by entomologists because they are virulent insect pathogens. They form a symbiotic
relationship with nematodes (Heterorhabditis sp.) that invade the larvae of insects. The nematodes regurgitate the
bacteria, which kill the insects and provide a food source for the nematodes. Insect-pathogenic nematodes are thought
to be harmless to vertebrates and are used in horticulture for biologic control of insects (6).

P. asymbiotica is a human pathogen, the source of which has not previously been identified. First described in 1989 by
Farmer et al. (7), P. asymbiotica has been associated with invasive soft tissue and disseminated bacteremic infections
in the United States and Australia. Multifocal skin and soft tissue abscesses are characteristic. Reported predominantly
from Texas and the eastern coast of Australia, P. asymbiotica infections have been associated with outdoor activity
during the warm summer months (8). Because this bacterium was not believed to be associated with nematodes, it was
given the name asymbiotica (not a symbiont) in 1999 (5).

The organism can be isolated from soft tissue or blood samples and grows readily on conventional bacterial culture
media. However, because clinical microbiology laboratories may misidentify P. asymbiotica, the true frequency of
human infection is uncertain (9).