RESUMO
Helicobacter heilmannii naturally colonizes the stomachs of dogs and cats and has been associated with gastric disorders in humans. Nine feline Helicobacter strains, classified as H. heilmannii based on ureAB and 16S rRNA gene sequences, were divided into a highly virulent and a low-virulence group. The genomes of these strains were sequenced to investigate their phylogenetic relationships, to define their gene content and diversity, and to determine if the differences in pathogenicity were associated with the presence or absence of potential virulence genes. The capacities of these helicobacters to bind to the gastric mucosa were investigated as well. Our analyses revealed that the low-virulence strains do not belong to the species H. heilmannii but to a novel, closely related species for which we propose the name Helicobacter ailurogastricus. Several homologs of H. pylori virulence factors, such as IceA1, HrgA, and jhp0562-like glycosyltransferase, are present in H. heilmannii but absent in H. ailurogastricus. Both species contain a VacA-like autotransporter, for which the passenger domain is remarkably larger in H. ailurogastricus than in H. heilmannii. In addition, H. ailurogastricus shows clear differences in binding to the gastric mucosa compared to H. heilmannii. These findings highlight the low-virulence character of this novel Helicobacter species.
Assuntos
Mucosa Gástrica/microbiologia , Gastrite/microbiologia , Helicobacter heilmannii/genética , Helicobacter heilmannii/patogenicidade , Mucosa Intestinal/microbiologia , Animais , Aderência Bacteriana/genética , Proteínas de Bactérias/genética , Gatos , Linhagem Celular , Desoxirribonucleases de Sítio Específico do Tipo II/genética , Cães , Células Epiteliais/microbiologia , Mucosa Gástrica/citologia , Gerbillinae , Glicosiltransferases/genética , Infecções por Helicobacter/microbiologia , Helicobacter heilmannii/classificação , Humanos , Mucosa Intestinal/citologia , Dados de Sequência Molecular , Filogenia , Estrutura Terciária de Proteína , RNA Ribossômico 16S/genética , Virulência/genética , Zoonoses/microbiologiaRESUMO
Structure-based virtual screening was performed against the target dipeptidyl peptidase IV (DPP-IV) to identify good chemical starting points for medicinal chemistry. A database of available compounds was filtered by calculated physical properties and undesired chemistry. This database was matched against two in-house designed DPP-IV pharmacophores, and the hits from these pharmacophore searches were docked into a DPP-IV crystal structure. Compounds were then selected for testing and 51 active compounds were identified from a list of 4000 compounds tested. These had activities ranging from 30% to 82% when tested at a concentration of 30 microM in an enzyme inhibition assay.