Expression of BfrH, a Putative Siderophore Receptor of Bordetella bronchiseptica , Is Regulated by Iron, Fur1, and the Extracellular Function Sigma Factor EcfI

Abstract

Iron (Fe) in soluble elemental form is found in the tissues and fluids of animals at concentrations insufficient for sustaining growth of bacteria. Consequently, to promote colonization and persistence, pathogenic bacteria evolved a myriad of scavenging mechanisms to acquire Fe from the host. Bordetella bronchiseptica, the etiologic agent of upper respiratory infections in a wide range of mammalian hosts, expresses a number of proteins for acquisition of Fe. Using proteomic and genomic approaches, three Fe-regulated genes were identified in the bordetellae: bfrH, a gene encoding a putative siderophore receptor; ecfI, a gene encoding a putative extracellular function (ECF) sigma factor; and ecfR, a gene encoding a putative EcfI modulator. All three genes are highly conserved in B. pertussis, B. parapertussis, and B. avium. Genetic analysis revealed that transcription of bfrH was coregulated by ecfI, ecfR, and fur1, one of two fur homologues carried by B. bronchiseptica. Overexpression of ecfI decoupled bfrH from Fe-dependent regulation. In contrast, expression of bfrH was significantly reduced in an ecfI deletion mutant. Deletion of ecfR, however, was correlated with a significant increase in expression of bfrH, due in part to a cis-acting nucleotide sequence within ecfR which likely reduces the frequency of readthrough transcription of bfrH from the Fe-dependent ecfIR promoter. Using a murine competition infection model, bfrH was shown to be required for optimal virulence of B. bronchiseptica. These experiments revealed ecfIR-bfrH as a locus encoding a new member of the growing family of Fe and ECF sigma factor-modulated regulons in the bordetellae.

Transcriptional Profiling of the Iron Starvation Response in Bordetella pertussis Provides New Insights into Siderophore Utilization and Virulence Gene Expression

“…BP1136 encodes an extracytoplasmic function sigma factor; this gene is an ortholog of the B. bronchiseptica ecfI gene adjacent to and required for expression of bfrH (BB3658/BP1138), encoding a TonB-dependent receptor of unknown ligand specificity (27). Other upregulated genes adjacent to predicted TonB-dependent iron source receptor genes included BP1961 near bfrI (BP1962) and BP0454 near hemC (BP0456).…”

Comparative Phosphoproteomics of Classical Bordetellae Elucidates the Potential Role of Serine, Threonine and Tyrosine Phosphorylation in Bordetella Biology and Virulence

“…In addition, four other virulence factors were also phosphorylated in one or more Bordetella species ( Table 2 ). Three were involved in iron acquisition including BfrH, a siderophore receptor ( Burgos et al., 2010 ), as well as AlcA and AlcC, both of which are involved in the synthesis of the alcaligin siderophore. BfrH was phosphorylated in both B. pertussis and B. bronchiseptica while AlcA and AlcC was only phosphorylated in B. pertussis and B. parapertussis respectively.…”

Caracterización molecular y funcional de la respuesta de la acidez en Bordetella bronchiseptica

“…B. bronchiseptica es capaz de responder y adaptarse a concentraciones cambiantes de hierro, mediante un complejo mecanismo regulatorio [188][189]. Esta capacidad de respuesta, Bvg-independiente [190][191], desempeña un importante papel durante el proceso infectivo [188][189].…”

“…Interesentamente, esta última proteína puede desempeñar un importante rol en el desarrollo de ATR [208,241]. Si bien no hemos analizado este último aspecto, el genoma secuenciado de la cepa de B. bronchiseptica RB50, posee dos ORF para la proteína Fur (BB0215 y BB3942) [98,191]. Al menos una de estos dos codifica para un producto funcional que responde de manera análoga a cambios en la concentración de de hierro con genes equivalentes de otras bacterias Gram negativas [188][189][190][191].…”

“…El estudio metabolismo del hierro en B. bronchiseptica se ha limitado mayormente a una serie de mecanismos que dispone éste patógeno para secuestrar hierro a partir del huésped durante su tránsito in vivo. Estos incluyen, al sideróforo Alcaligina (FauA), el xenosideróforo Enterobactina (BfeA) y los sistemas de captura de Hemina (BfrH) y Hemoglobina (BhuR) [188][189]191]. La expresión de todos ellos tiene, en mayor o menor grado, efectos sobre el desarrollo del proceso infectivo [188].…”