title: Thermolysin damages animal life through degradation of plasma proteins enhanced by rapid cleavage of serpins and activation of proteases.
abstract: Thermolysin, a metallopeptidase secreted by pathogenic microbes, is concluded as an important virulence factor due to cleaving purified host proteins in vitro. Using the silkworm Bombyx mori as a model system, we found that thermolysin injection into larvae induces the destruction of the coagulation response and the activation of hemolymph melanization, which results in larval death. Thermolysin triggers the rapid degradation of insect and mammalian plasma proteins at a level that is considerably greater than expected in vitro and/or in vivo. To more specifically explore the mechanism, thermolysin-induced changes to key proteins belonging to the insect melanization pathway were assessed as a window for observing plasma protein cleavage. The application of thermolysin induced the rapid cleavage of the melanization negative regulator serpin-3, but did not directly activate the melanization rate-limiting enzyme prophenoloxidase (PPO) or the terminal serine proteases responsible for PPO activation. Terminal serine proteases of melanization are activated indirectly after thermolysin exposure. We hypothesize that thermolysin induces the rapid degradation of serpins and the activation of proteases directly or indirectly, boosting uncontrolled plasma protein degradation in insects and mammalians.
authors.affiliation: College of Life Science, Anhui Agricultural University, Changjiang, People's Republic of China; College of Agriculture and Biology, Shanghai Jiaotong University, Dongchuan, Shanghai, People's Republic of China; Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Kong
authors.forename: Anrui
authors.initials: A
authors.lastname: Lu
authors.forename: Jingmin
authors.initials: J
authors.lastname: Guan
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.forename: Muwang
authors.initials: M
authors.lastname: Li
authors.forename: Julián F
authors.initials: JF
authors.lastname: Hillyer
authors.forename: Nalini
authors.initials: N
authors.lastname: Ramarao
authors.forename: Kenneth
authors.initials: K
authors.lastname: Söderhäll
authors.forename: Chaoliang
authors.initials: C
authors.lastname: Liu
authors.forename: Erjun
authors.initials: E
authors.lastname: Ling
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D012831:Bombyx / Q000187:drug effects* / Q000276:immunology; D004156:Catechol Oxidase; D004331:Drosophila melanogaster / Q000378:metabolism; D004792:Enzyme Precursors; D006458:Hemolymph / Q000378:metabolism; D019476:Insect Proteins / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000276:immunology; D008543:Melanins / Q000096:biosynthesis; D010447:Peptide Hydrolases / Q000378:metabolism*; D012697:Serine Endopeptidases; D057057:Serine Proteases; D015843:Serpins / Q000378:metabolism; D013820:Thermolysin / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D004792:Enzyme Precursors; D019476:Insect Proteins; D008543:Melanins; D015843:Serpins; D037521:Virulence Factors; C038451:pro-phenoloxidase; D004156:Catechol Oxidase; D010447:Peptide Hydrolases; D057057:Serine Proteases; D012697:Serine Endopeptidases; D013820:Thermolysin
keywords: cleavage; plasma; thermolysin