title: Nicotinic acid modulates Legionella pneumophila gene expression and induces virulence traits.
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.
authors: Cellular and Molecular Biology Program, Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors: Rachel L
authors: RL
authors: Edwards
authors: Andrew
authors: A
authors: Bryan
authors: Matthieu
authors: M
authors: Jules
authors: Kaoru
authors: K
authors: Harada
authors: Carmen
authors: C
authors: Buchrieser
authors: Michele S
authors: MS
authors: Swanson
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D049109:Cell Proliferation; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D016952:Legionella pneumophila / Q000187:drug effects* / Q000378:metabolism* / Q000472:pathogenicity; D008247:Lysosomes; D008264:Macrophages; D051379:Mice; D008958:Models, Molecular; D009525:Niacin / Q000494:pharmacology*; D011487:Protein Conformation; D013997:Time Factors; D059467:Transcriptome; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; C068355:CcdA protein, Bacteria; D009525:Niacin