The Haemophilus ducreyi Fis Protein Is Involved in Controlling Expression of thelspB-lspA2Operon and Other Virulence Factors

Abstract

ABSTRACTExpression of thelspB-lspA2operon encoding a virulence-related two-partner secretion system inHaemophilus ducreyi35000HP is directly regulated by the CpxRA regulatory system (M. Labandeira-Rey, J. R. Mock, and E. J. Hansen, Infect. Immun. 77:3402–3411, 2009). In the present study, we show that this secretion system is also regulated by the small nucleoid-associated protein Fis. Inactivation of theH. ducreyi fisgene resulted in a reduction in expression of both theH. ducreyiLspB and LspA2 proteins. DNA microarray experiments showed that aH. ducreyi fisdeletion mutant exhibited altered expression levels of genes encoding other importantH. ducreyivirulence factors, including DsrA and Flp1, suggesting a possible global role for Fis in the control of virulence in this obligate human pathogen. While theH. ducreyiFis protein has a high degree of sequence and structural similarity to the Fis proteins of other bacteria, its temporal pattern of expression was very different from that of enterobacterial Fis proteins. The use of alacZ-based transcriptional reporter provided evidence which indicated that theH. ducreyiFis homolog is a positive regulator ofgyrB, a gene that is negatively regulated by Fis in enteric bacteria. Taken together, the Fis protein expression data and the observed regulatory effects of Fis inH. ducreyisuggest that this small DNA binding protein has a regulatory role inH. ducreyiwhich may differ in substantial ways from that of other Fis proteins.