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  • Nicotinic acid modulates Legionella pneumophila gene expression and induces virulence traits.

Nicotinic acid modulates Legionella pneumophila gene expression and induces virulence traits.

Infection and immunity (2013-01-16)
Rachel L Edwards, Andrew Bryan, Matthieu Jules, Kaoru Harada, Carmen Buchrieser, Michele S Swanson
ABSTRACT

In response to environmental fluctuations or stresses, bacteria can activate transcriptional and phenotypic programs to coordinate an adaptive response. The intracellular pathogen Legionella pneumophila converts from a noninfectious replicative form to an infectious transmissive form when the bacterium encounters alterations in either amino acid concentrations or fatty acid biosynthesis. Here, we report that L. pneumophila differentiation is also triggered by nicotinic acid, a precursor of the central metabolite NAD(+). In particular, when replicative L. pneumophila are treated with 5 mM nicotinic acid, the bacteria induce numerous transmissive-phase phenotypes, including motility, cytotoxicity toward macrophages, sodium sensitivity, and lysosome avoidance. Transcriptional profile analysis determined that nicotinic acid induces the expression of a panel of genes characteristic of transmissive-phase L. pneumophila. Moreover, an additional 213 genes specific to nicotinic acid treatment were altered. Although nearly 25% of these genes lack an assigned function, the gene most highly induced by nicotinic acid treatment encodes a putative major facilitator superfamily transporter, Lpg0273. Indeed, lpg0273 protects L. pneumophila from toxic concentrations of nicotinic acid as judged by analyzing the growth of the corresponding mutant. The broad utility of the nicotinic acid pathway to couple central metabolism and cell fate is underscored by this small metabolite's modulation of gene expression by diverse microbes, including Candida glabrata, Bordetella pertussis, Escherichia coli, and L. pneumophila.

MATERIALS
Product Number
Brand
Product Description

Supelco
Nicotinic acid, analytical standard
Sigma-Aldrich
Nicotinic acid sodium salt, 98%
Sigma-Aldrich
Nicotinic acid, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥98%
Sigma-Aldrich
Nicotinic acid, ≥98%
Sigma-Aldrich
Nicotinic acid, meets USP testing specifications
Sigma-Aldrich
Nicotinic acid, ≥99.5% (HPLC)
Supelco
Niacin (Nicotinic Acid), Pharmaceutical Secondary Standard; Certified Reference Material