The Bordetella bronchiseptica nic locus encodes a nicotinic acid degradation pathway and the 6‐hydroxynicotinate‐responsive regulator BpsR

Abstract

The classical Bordetella species use amino acids as carbon sources and can catabolize organic acids and tricarboxylic acid cycle intermediates. They are also auxotrophic for nicotinamide adenine dinucleotide (NAD) pathway precursors such as nicotinic acid. Bordetellae have a putative nicotinate catabolism gene locus highly similar to that characterized in Pseudomonas putida KT2440. This study determined the distribution of the nic genes among Bordetella species and analyzed the regulation of this nicotinic acid degradation system. Transcription of the Bordetella bronchiseptica nicC gene was repressed by the NicR ortholog, BpsR, previously shown to regulate extracellular polysaccharide synthesis genes. nicC expression was derepressed by nicotinic acid or by the first product of the degradation pathway, 6-hydroxynicotinic acid, which was shown to be the inducer. Results using mutants with either a hyperactivated pathway or an inactivated pathway showed a marked effect on growth on nicotinic acid that indicated this degradation pathway influences NAD biosynthesis. Pathway dysregulation also affected Bordetella BvgAS-mediated virulence gene regulation, demonstrating that fluctuation of intracellular nicotinic acid pools impacts Bvg phase transition responses.

The Transcriptional Regulator BpsR Controls the Growth of Bordetella bronchiseptica by Repressing Genes Involved in Nicotinic Acid Degradation

“…Results very similar to ours were recently reported by Brickman and Armstrong (29). However, these authors did not report a restoration of the growth of the bpsR mutant due to the deletion of the nicA gene, the binding of BpsR to the nic promoter, and the effect of NA and 6-HNA on this binding.…”

Conquering the host: Bordetella spp. and Pseudomonas aeruginosa molecular regulators in lung infection

“…breaks down erythrocytes to have access to the iron. The iron starvation response is mediated by Fur ( Brickman and Armstrong, 1995 , 2018 ), which responds to the presence of cathecolamines ( Brickman et al, 2011 ) or blood and serum ( Gestal et al, 2018 ). But iron stress even promotes binding to the respiratory epithelia ( Vidakovics et al, 2007 ) indicating that is not simply a nutritional exchange but also it is involved in the virulence and attachment.…”

“…has also genetic and metabolic similarities with Pseudomonas spp. ( Gross et al, 2008 ; Brickman and Armstrong, 2018 ). Both have evolved from environmental origins ( Mathee et al, 2008 ), and both have evolved a variety of virulence mechanisms that allows them to be adaptable to different environmental stressors, including host immune responses ( Hauser, 2011 ; Gestal et al, 2019a , b ; Qin et al, 2022 ).…”

Structural mechanism for regulation of DNA binding of BpsR, a Bordetella regulator of biofilm formation, by 6-hydroxynicotinic acid

“…Recently, we and others have shown that BpsR controls the growth of B . bronchiseptica by repressing genes involved in nicotinic acid (NA) degradation [16,17]. Nicotinic acid or nicotinamide is essential for the growth of many pathogenic Bordetella species in the laboratory.…”

“…pertussis , and B . parapertussis [16,17] with a similar pathway conserved in other bacteria [18,19]. In the first step of degradation, NA is oxidized to 6-hydroxynicotinic acid (6HNA) by the nicA and nicB gene products [18,19].…”