Regulation of Expression of the Haemophilus ducreyi LspB and LspA2 Proteins by CpxR
| Autor: | Eric J. Hansen, Maria Labandeira-Rey, Jason R. Mock |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
DNA
Bacterial Sexually transmitted disease medicine.medical_specialty Operon Immunology Virulence Electrophoretic Mobility Shift Assay urologic and male genital diseases Microbiology Haemophilus ducreyi Gene Knockout Techniques Bacterial Proteins Lectins Molecular genetics medicine Humans Promoter Regions Genetic Pathogen Gene Oligonucleotide Array Sequence Analysis biology Gene Expression Profiling Gene Expression Regulation Bacterial medicine.disease biology.organism_classification Molecular Pathogenesis Virology Chancroid female genital diseases and pregnancy complications Infectious Diseases bacteria Parasitology Bacterial Outer Membrane Proteins Protein Binding Signal Transduction |
| Zdroj: | Infection and Immunity. 77:3402-3411 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00292-09 |
| Popis: | Haemophilus ducreyi is a gram-negative coccobacillus and the causative agent of the sexually transmitted genital ulcer disease (GUD) chancroid (1, 8). Globally, chancroid is a significant sexually transmitted disease, with more than 6 million cases reported in 1997 (60). In the United States, several outbreaks were reported between 1980 and 2000 (24, 36, 51), but since then the number of cases has greatly diminished, and today the soft chancres characteristic of H. ducreyi infection occur only in isolated cases that are typically associated with the sex trade industry (57). Chancroid is endemic in some developing countries in Africa, Asia, and South America, where it accounts for almost half of all GUD cases, although these numbers could be higher as H. ducreyi cases remain poorly documented (55, 57). GUD is a recognized cofactor for human immunodeficiency virus acquisition and transmission (25, 37), and a better understanding of H. ducreyi pathogenesis is necessary to allow a rational approach to the identification of vaccine candidates that could be used to prevent chancroid. H. ducreyi is a strict human pathogen, and it is likely that during the different stages of ulcer production (i.e., progression of a papule into a pustule followed by frank ulceration [1, 8, 50]), this pathogen controls gene expression to enhance its growth and to evade the host immune system. Information about regulatory networks that might control the expression of H. ducreyi virulence factors is very limited at present. Although nucleotide sequence analysis of the H. ducreyi 35000HP genome (GenBank accession no. NC002940) revealed the presence of several genes encoding predicted proteins with homology to known bacterial regulators, to date, only the fur gene (12), the groE operon (44), and the dnaK-dnaJ operon (43) have been studied in any detail. The LspA1, LspA2, and LspB proteins constitute a two-partner secretion system in H. ducreyi (65). Expression of either LspA1 or LspA2 has been shown to be necessary for H. ducreyi to inhibit phagocytosis by immune cells in vitro (61). LspA1 and LspA2 have 86% identity (64), and their respective open reading frames (ORFs) are located very distant from each other in the H. ducreyi chromosome. These proteins are also required for full virulence of this pathogen in both the human (30) and the temperature-dependent rabbit (63) models of experimental H. ducreyi infection. Previous studies in our laboratory indicated that wild-type H. ducreyi apparently expressed more LspA1 than LspA2 and that a lspA1 mutant expressed increased amounts of LspA2 (63). Taken together, these results suggested that these two proteins might be under the control of different, unidentified regulatory factors. In the present study, we report that inactivation of the gene encoding the response regulator CpxR resulted in increased expression of both LspB and LspA2, suggesting that the H. ducreyi lspB-lspA2 operon is under the control of the CpxRA two-component regulatory system (18, 46, 47) homolog present in H. ducreyi. |
| Databáze: | OpenAIRE |
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