Talaromyces marneffei Mp1 Protein, a Novel Virulence Factor, Carries Two Arachidonic Acid-Binding Domains To Suppress Inflammatory Responses in Hosts

Lam, Wai-Hei1; Sze, Kong-Hung2,3,4,5; Ke, Yihong2,3,4,5; Tse, Man-Kit2,3,4,5; Zhang, Hongmin1,6,7,8; Woo, Patrick C. Y.2,3,4,5; Lau, Susanna K. P.2,3,4,5; Lau, Candy C. Y.2,3,4,5; Xu, Simin2,3,4,5; Lai, Pok-Man2,3,4,5; Zhou, Ting2,3,4,5; Antonyuk, Svetlana, V9; Kao, Richard Y. T.2,3,4,5; Yuen, Kwok-Yung2,3,4,5; Hao, Quan1,6

2019-04

10.1128/IAI.00679-18

INFECTION AND IMMUNITY   影响因子和分区

0019-9567

1098-5522

Talaromyces marneffei infection causes talaromycosis (previously known as penicilliosis), a very important opportunistic systematic mycosis in immunocompromised patients. Different virulence mechanisms in T. marneffei have been proposed and investigated. In the sera of patients with talaromycosis, Mp1 protein (Mp1p), a secretory galactomannoprotein antigen with two tandem ligand-binding domains (Mp1p-LBD1 and Mp1p-LBD2), was found to be abundant. Mp1p-LBD2 was reported to possess a hydrophobic cavity to bind copurified palmitic acid (PLM). It was hypothesized that capturing of lipids from human hosts by expressing a large quantity of Mp1p is a virulence mechanism of T. marneffei. It was shown that expression of Mp1p enhanced the intracellular survival of T. marneffei by suppressing proinflammatory responses. Mechanistic study of Mp1p-LBD2 suggested that arachidonic acid (AA), a precursor of paracrine signaling molecules for regulation of inflammatory responses, is the major physiological target of Mp1p-LBD2. In this study, we use crystallographic and biochemical techniques to further demonstrate that Mp1p-LBD1, the previously unsolved first lipid binding domain of Mp1p, is also a strong AA-binding domain in Mp1p. These studies on Mp1p-LBD1 support the idea that the highly expressed Mp1p is an effective AA-capturing protein. Each Mp1p can bind up to 4 AA molecules. The crystal structure of Mp1p-LBD1-LBD2 has also been solved, showing that both LBDs are likely to function independently with a flexible linker between them. T. marneffei and potentially other pathogens highly expressing and secreting proteins similar to Mp1p can severely disturb host signaling cascades during proinflammatory responses by reducing the availabilities of important paracrine signaling molecules.

X-ray crystallography arachidonic acid (AA) lipid-protein interaction nuclear magnetic resonance virulence factors

SCI

英语

其他

European Community[283570] ; European Community[2370/5437]

Immunology ; Infectious Diseases

Immunology ; Infectious Diseases

WOS:000462160400009

AMER SOC MICROBIOLOGY

IMMUNOLOGY

Web of Science

1.Univ Hong Kong, Sch Biomed Sci, Hong Kong, Peoples R China
2.Univ Hong Kong, State Key Lab Emerging Infect Dis, Hong Kong, Peoples R China
3.Univ Hong Kong, Dept Microbiol, Hong Kong, Peoples R China
4.Univ Hong Kong, Res Ctr Infect & Immun, Hong Kong, Peoples R China
5.Univ Hong Kong, Carol Yu Ctr Infect, Hong Kong, Peoples R China
6.Univ Hong Kong, Shenzhen Inst Innovat & Res, Shenzhen, Peoples R China
7.Southern Univ Sci & Technol, Dept Biol, Shenzhen, Peoples R China
8.Southern Univ Sci & Technol, Shenzhen Key Lab Cell Microenvironm, Shenzhen, Peoples R China
9.Univ Liverpool, Mol Biophys Grp, Liverpool, Merseyside, England

Lam, Wai-Hei,Sze, Kong-Hung,Ke, Yihong,et al. Talaromyces marneffei Mp1 Protein, a Novel Virulence Factor, Carries Two Arachidonic Acid-Binding Domains To Suppress Inflammatory Responses in Hosts[J]. INFECTION AND IMMUNITY,2019,87(4).

Lam, Wai-Hei.,Sze, Kong-Hung.,Ke, Yihong.,Tse, Man-Kit.,Zhang, Hongmin.,...&Hao, Quan.(2019).Talaromyces marneffei Mp1 Protein, a Novel Virulence Factor, Carries Two Arachidonic Acid-Binding Domains To Suppress Inflammatory Responses in Hosts.INFECTION AND IMMUNITY,87(4).

Lam, Wai-Hei,et al."Talaromyces marneffei Mp1 Protein, a Novel Virulence Factor, Carries Two Arachidonic Acid-Binding Domains To Suppress Inflammatory Responses in Hosts".INFECTION AND IMMUNITY 87.4(2019).