title: Molecular evolution of the nicotinic acid requirement within the Shigella/EIEC pathotype.
abstract: Nicotinamide adenine dinucleotide (NAD) is a crucial cofactor in several anabolic and catabolic reactions. NAD derives from quinolinic acid (QUIN) which in Escherichia coli is obtained through a pyridine salvage pathway or a de novo synthesis pathway. In the latter case, two enzymes, L-aspartate oxidase (NadB) and quinolinate synthase (NadA), are required for the synthesis of QUIN. In contrast to its E. coli ancestor, Shigella spp., the causative agent of bacillary dissentery, lacks the de novo pathway and strictly requires nicotinic acid for growth (Nic⁻ phenotype). This phenotype depends on the silencing of the nadB and nadA genes and its pathoadaptive nature is suggested by the observation that QUIN attenuates the Shigella invasive process. Shigella shares the pathogenicity mechanism with enteronvasive E. coli (EIEC), a group of pathogenic E. coli. On the basis of this similarity EIEC and Shigella have been grouped into a single E. coli pathotype. However EIEC strains do not constitute a homogeneous group and do not possess the complete set of characters that define Shigella strains. In this work we have analysed thirteen EIEC strains belonging to different serotypes and originating from different geographic areas. We show that, in contrast to Shigella, only some EIEC strains require nicotinic acid for growth in minimal medium. Moreover, by studying the emergence of the Nic⁻ phenotype in all serotypes of S. flexneri, as well as in S. sonnei and S. dysenteriae, we describe which molecular rearrangements occurred and which mutations are responsible for the inactivation of the nadA and nadB genes. Our data confirm that the genome of Shigella is extremely dynamic and support the hypothesis that EIEC might reflect an earlier stage of the pathoadaptation process undergone by Shigella.
authors.affiliation: Dipartimento di Scienze, Università Roma Tre, Viale G. Marconi 446, 00146 Roma, Italy.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Di Martino
authors.forename: Rosa
authors.initials: R
authors.lastname: Fioravanti
authors.forename: Giada
authors.initials: G
authors.lastname: Barbabella
authors.forename: Gianni
authors.initials: G
authors.lastname: Prosseda
authors.forename: Bianca
authors.initials: B
authors.lastname: Colonna
authors.forename: Mariassunta
authors.initials: M
authors.lastname: Casalino
mesh_terms: D000220:Adaptation, Biological; D003470:Culture Media / Q000737:chemistry; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008969:Molecular Sequence Data; D009525:Niacin / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D012760:Shigella / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*
chemical_list: D003470:Culture Media; D004269:DNA, Bacterial; D009525:Niacin
keywords: Evolution; NAD biosynthesis; Pathoadaptive mutations; Pathogenic E. coli; Shigella