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Infection and Immunity, June 2000, p. 3657-3666, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

An OmpA-Like Protein from Acinetobacter spp. Stimulates Gastrin and Interleukin-8 Promoters

Ernest Ofori-Darko,1 Yana Zavros,2 Gabriele Rieder,1 Susan A. Tarlé,2 Mary Van Antwerp,2 and Juanita L. Merchant1,2,3,*

Howard Hughes Medical Institute2 and Departments of Internal Medicine1 and Physiology,3 University of Michigan, Ann Arbor, Michigan

Received 14 December 1999/Returned for modification 21 February 2000/Accepted 15 March 2000

Bacterial overgrowth in the stomach may occur under conditions of diminished or absent acid secretion. Under these conditions, secretion of the hormone gastrin is elevated. Alternatively, bacterial factors may directly stimulate gastrin. Consistent with this hypothesis, we found that mice colonized for 2 months with a mixed bacterial culture of opportunistic pathogens showed an increase in serum gastrin. To examine regulation of gene expression by bacterial proteins, stable transformants of AGS cells expressing gastrin or interleukin-8 (IL-8) promoters were cocultured with live organisms. Both whole-cell sonicates and a heat-stable fraction were also coincubated with the cells. A level of 108 organisms per ml stimulated both the gastrin and IL-8 promoters. Heat-stable proteins prepared from these bacterial sonicates stimulated the promoter significantly more than the live organism or unheated sonicates. A 38-kDa heat-stable protein stimulating the gastrin and IL-8 promoters was cloned and found to be an OmpA-related protein. Immunoblotting using antibody to the OmpA-like protein identified an Acinetobacter sp. as the bacterial species that expressed this protein and colonized the mouse stomach. Moreover, reintubation of mice with a pure culture of the Acinetobacter sp. caused gastritis. We conclude that bacterial colonization of the stomach may increase serum gastrin levels in part through the ability of the bacteria to produce OmpA-like proteins that directly stimulate gastrin and IL-8 gene expression. These results implicate OmpA-secreting bacteria in the activation of gastrin gene expression and raise the possibility that a variety of organisms may contribute to the increase in serum gastrin and subsequent epithelial cell proliferation in the hypochlorhydric stomach.

* Corresponding author. Mailing address: 1150 West Medical Dr., MSRB I, 3510, Ann Arbor, MI 48109-0650. Phone: (734) 647-2944. Fax: (734) 936-1400. E-mail: merchanj{at}umich.edu.

Infection and Immunity, June 2000, p. 3657-3666, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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