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Infection and Immunity, January 2002, p. 5-10, Vol. 70, No. 1
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.1.5-10.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Escherichia coli Hemoglobin Protease Autotransporter Contributes to Synergistic Abscess Formation and Heme-Dependent Growth of Bacteroides fragilis

Ben R. Otto,1* Silvy J. M. van Dooren,1 Charles M. Dozois ,2,{dagger} Joen Luirink,1 and Bauke Oudega1

Department of Molecular Microbiology, Institute of Molecular Biological Sciences, Amsterdam, The Netherlands,1 Department of Biology, Washington University, St. Louis, Missouri2

Received 2 March 2001/ Returned for modification 28 May 2001/ Accepted 10 October 2001

Intra-abdominal infections (IAI) continue to be a serious clinical problem. Bacterial synergism is an important factor that influences the shift from contamination to IAI, leading to the development of lesions and abscess formation. Escherichia coli and Bacteroides fragilis are particularly abundant in IAI. The underlying molecular mechanisms of this pathogenic synergy are still unclear. The role of the hemoglobin protease (Hbp) autotransporter protein from E. coli in the synergy of IAI was investigated. Hbp is identical to Tsh, a temperature-sensitive hemagglutinin associated with avian pathogenic E. coli. Clinical isolates from miscellaneous extraintestinal infections were phenotypically and genotypically screened for Hbp. The presence of Hbp was significantly associated with E. coli isolated from IAI and other extraintestinal infections. In a murine infection model, Hbp was shown to contribute to the pathogenic synergy of abscess development. Mice immunized with Hbp were protected against mixed infections and did not develop abscess lesions. Furthermore, an E. coli wild-type strain that did not induce abscess formation in the synergy model was transformed with a plasmid encoding the hbp gene, and mixed infections with this strain lead to increased growth of B. fragilis and induction of abscess lesions. Growth-promoting studies showed that purified Hbp is able to deliver heme to B. fragilis strain BE1. In conclusion, results suggest the synergy of abscess formation by E. coli and B. fragilis can be partly explained by the capacity of B. fragilis to intercept Hbp and iron from heme to overcome the iron restrictions imposed by the host.

* Corresponding author. Mailing address: Department of Molecular Microbiology, Institute of Molecular Biological Sciences, De Boelelaan 1087, 1081 HV Amsterdam, The Netherlands. Phone: 31-20-4447036. Fax: 31-20-4446979. E-mail: brotto{at}bio.vu.nl.

Editor: B. B. Finlay

{dagger} Present address: INRS—Institut Armand-Frappier Microbiologie et Immunologie, Laval, Quebec, Canada.

Infection and Immunity, January 2002, p. 5-10, Vol. 70, No. 1
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.1.5-10.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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