更新于：2024-11-01

Bacterial adhesin

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 Bacterial adhesin 相关的药物

VCD-088

靶点

Bacterial adhesin

作用机制

细菌粘附素拮抗剂

在研机构

The Brigham & Women's Hospital, Inc.

原研机构

Vyome Therapeutics, Inc.

在研适应症-

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 Bacterial adhesin 相关的临床结果

登录后查看更多信息

100 项与 Bacterial adhesin 相关的转化医学

登录后查看更多信息

0 项与 Bacterial adhesin 相关的专利（医药）

登录后查看更多信息

项与 Bacterial adhesin 相关的文献（医药）

2024-10-01·Proceedings of the National Academy of Sciences

Structural basis for adhesin secretion by the outer-membrane usher in type 1 pili

Article

作者: Dodson, Karen W. ; Summers, Brock T. ; Pinkner, Jerome S. ; Zimmerman, Maxwell I. ; Hultgren, Scott J. ; Yuan, Peng ; Bitter, Ryan M.

Gram-negative bacteria produce chaperone–usher pathway pili, which are extracellular protein fibers tipped with an adhesive protein that binds to a receptor with stereochemical specificity to determine host and tissue tropism. The outer-membrane usher protein, together with a periplasmic chaperone, assembles thousands of pilin subunits into a highly ordered pilus fiber. The tip adhesin in complex with its cognate chaperone activates the usher to allow extrusion across the outer membrane. The structural requirements to translocate the adhesin through the usher pore from the periplasm to the extracellular space remains incompletely understood. Here, we present a cryoelectron microscopy structure of a quaternary tip complex in the type 1 pilus system from Escherichia coli , which consists of the usher FimD, chaperone FimC, adhesin FimH, and the tip adapter FimF. In this structure, the usher FimD is caught in the act of secreting its cognate adhesin FimH. Comparison with previous structures depicting the adhesin either first entering or having completely exited the usher pore reveals remarkable structural plasticity of the two-domain adhesin during translocation. Moreover, a piliation assay demonstrated that the structural plasticity, enabled by a flexible linker between the two domains, is a prerequisite for adhesin translocation through the usher pore and thus pilus biogenesis. Overall, this study provides molecular details of adhesin translocation across the outer membrane and elucidates a unique conformational state adopted by the adhesin during stepwise secretion through the usher pore. This study elucidates fundamental aspects of FimH and usher dynamics critical in urinary tract infections and is leading to antibiotic-sparing therapeutics.

2023-06-01·Poultry Science

Collagen adhesin protein and necrotic enteritis B-like toxin as biomarkers for early diagnosis of necrotic enteritis in commercial broiler chickens

Article

作者: Nam, H ; Li, C ; Goo, D ; Smith, A H ; Lee, Y ; Rehberger, T G ; Park, I ; Sawall, J ; Lillehoj, H S

Mouse monoclonal antibodies (mAbs) reactive with Clostridium perfringens collagen adhesin protein (CNA) and necrotic enteritis B-like toxin (NetB) were developed. The best capture/detection mAb pairs for CNA and NetB were selected based on their affinity and specificity to develop sandwich enzyme-linked immunosorbent assays (ELISAs) to detect CNA and NetB proteins, respectively, in jejunal digesta samples from commercial broiler farms in the United States. Prior to the analysis of samples from commercial broiler flocks, the specificity and sensitivity of the CNA and NetB ELISAs were validated using sera, jejunal digesta, and fecal samples from chickens coinfected with Eimeria maxima and CNA⁺/NetB⁺C. perfringens in an animal model of necrotic enteritis (NE). Subsequently, a total of 251 field samples were collected from 74 commercial poultry farms. Among these, 18 samples were from 6 broiler farms that used certified organics (CO), and 155 samples were from 42 farms with nonantibiotics (NA). In jejunal digesta samples, CNA levels ranged from 0.02 to 0.59 ng/mL and NetB levels ranged from 0.09 to 1.91 ng/mL. CNA and NetB levels showed a positive correlation with each other (Pearson correlation coefficient r = 0.772, P < 0.001). CNA and NetB levels in jejunal digesta were significantly decreased in CO farms compared with those from NA farms (P < 0.001). In conclusion, these new C. perfringens antigen-specific sandwich ELISAs offer a sensitive and specific means to detect C. perfringens CNA and NetB proteins as biomarkers of early NE occurrence in field samples from commercial broiler chickens.

2023-05-30·Pathogens (Basel, Switzerland)

Characterization of Collagen Binding Activity of Clostridium perfringens Strains Isolated from Broiler Chickens.

Article

作者: Sun, Zhifeng ; Lillehoj, Hyun ; Lee, Youngsub ; Lu, Mingmin ; Yan, Xianghe ; Li, Charles ; Goo, Doyun ; Yuan, Baohong

Clostridium perfringens is the etiological agent for necrotic enteritis (NE) in broiler chickens, which causes a substantial economic loss of an estimated USD 6 billion annually in the global poultry industry. Collagen adhesion is involved in the NE pathogenesis in poultry. In this study, the binding capabilities of chicken C. perfringens isolates of various genetic backgrounds (netB^-tpeL^-, netB⁺tpeL^-, netB⁺tpeL⁺) to collagen types I-V and gelatin were examined, and the putative adhesin protein cnaA gene was investigated at the genomic level. In total, 28 C. perfringens strains from healthy and NE-inflicted sick chickens were examined. The results on collagen adhesin-encoding gene cnaA by the quantitative-PCR results indicated that netB^-tpeL^- isolates had much lower copies of the detectable cnaA gene than netB⁺ isolates (10 netB⁺tpeL^- isolates, 5 netB⁺tpeL⁺ isolates). Most of the virulent C. perfringens isolates demonstrated collagen-binding abilities to types I-II and IV-V, while some strains showed weak or no binding to collagen type III and gelatin. However, the netB⁺tpeL⁺ isolates showed significantly higher binding capabilities to collagen III than netB^-tpeL^- and netB⁺tpeL^- isolates. The data in this study suggest that the collagen-binding capability of clinical C. perfringens isolates correlates well with their NE pathogenicity levels, especially for C. perfringens isolates carrying genes encoding crucial virulence factors and virulence-associated factors such as netB, cnaA, and tpeL. These results indicate that the presence of the cnaA gene may be correlated with C. perfringens virulence (particularly for netB⁺ isolates).