title: NafA negatively controls Neisseria meningitidis piliation.
abstract: Bacterial auto-aggregation is a critical step during adhesion of N. meningitidis to host cells. The precise mechanisms and functions of bacterial auto-aggregation still remain to be fully elucidated. In this work, we characterize the role of a meningococcal hypothetical protein, NMB0995/NMC0982, and show that this protein, here denoted NafA, acts as an anti-aggregation factor. NafA was confirmed to be surface exposed and was found to be induced at a late stage of bacterial adherence to epithelial cells. A NafA deficient mutant was hyperpiliated and formed bundles of pili. Further, the mutant displayed increased adherence to epithelial cells when compared to the wild-type strain. In the absence of host cells, the NafA deficient mutant was more aggregative than the wild-type strain. The in vivo role of NafA in sepsis was studied in a murine model of meningococcal disease. Challenge with the NafA deficient mutant resulted in lower bacteremia levels and mortality when compared to the wild-type strain. The present study reveals that meningococcal NafA is an anti-aggregation factor with strong impact on the disease outcome. These data also suggest that appropriate bacterial auto-aggregation is controlled by both aggregation and anti-aggregation factors during Neisseria infection in vivo.
authors: Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden. kuwae@lisci.kitasato-u.ac.jp
authors: Asaomi
authors: A
authors: Kuwae
authors: Hong
authors: H
authors: Sjölinder
authors: Jens
authors: J
authors: Eriksson
authors: Sara
authors: S
authors: Eriksson
authors: Yao
authors: Y
authors: Chen
authors: Ann-Beth
authors: AB
authors: Jonsson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D004847:Epithelial Cells / Q000166:cytology / Q000382:microbiology; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D006801:Humans; D008589:Meningococcal Infections / Q000097:blood / Q000382:microbiology; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009345:Neisseria meningitidis / Q000166:cytology* / Q000378:metabolism* / Q000472:pathogenicity; D015854:Up-Regulation
chemical_list: D001426:Bacterial Proteins