《微生物学》课程PPT课件讲稿（英文版）Lecture 3 Strategies for Studying Microbial Pathogenesis

Choosing an Animal model Pathogen may not affect animal at all OR may give different symptoms Given disease may have a number of animal models none of which fully satisfies characteristics of disease BIOL 533 Lecture three

BIOL 533 2 Lecture Three Choosing an Animal Model • Pathogen may not affect animal at all -OR￾may give different symptoms • Given disease may have a number of animal models, none of which fully satisfies characteristics of disease

Choosing an Animal model ep One model may show certain aspects of disease, but not another Different models may rely on different routes of introducing pathogen; e. g Bordetella pertussis ● Intracrania ● Interperitoneal Respiratory aspiration BIOL 533 Lecture three

BIOL 533 3 Lecture Three Choosing an Animal Model • One model may show certain aspects of disease, but not another • Different models may rely on different routes of introducing pathogen; e.g.: – Bordetella pertussis • Intracranial • Interperitoneal • Respiratory aspiration

Choosing an Animal model Ideally, want model to Use same route as human disease Display same symptoms Display same virulence Alternative: cell culture, organ culture BIOL 533 Lecture three

BIOL 533 4 Lecture Three Choosing an Animal Model • Ideally, want model to: – Use same route as human disease – Display same symptoms – Display same virulence • Alternative: cell culture, organ culture

Cell Culture/Organ Culture e Difficult Cell-lines often tumor lines that are genetically and physiologically different (immortal--many mutations) Removed from effects of other organs hormones · Cells grown in artificial media differ from∥Wivo Cell lines may not express same Ag on surface as When in animal BIOL 533 Lecture three

BIOL 533 5 Lecture Three Cell Culture/Organ Culture • Difficult • Cell-lines often tumor lines that are genetically and physiologically different (immortal—many mutations) • Removed from effects of other organs, hormones • Cells grown in artificial media differ from in vivo • Cell lines may not express same Ag on surface as when in animal

Studying Pathogenic Organisms a5 Look at phylogeny to find closely related organisms, for example S, typhimurium vs One may respond more easily than the other to variety of genetic techniques BIOL 533 Lecture three

BIOL 533 6 Lecture Three Studying Pathogenic Organisms • Look at phylogeny to find closely related organisms; for example: – S. typhimurium vs. – S. typhi One may respond more easily than the other to variety of genetic techniques

Studying Pathogenic Organisms a5 Look at other similar members of the same genus; for example M, smegmatis vs M tuberculosis M, smegmatis is faster-growing; methods may be applicable to M. tuberculosis BIOL 533 7 Lecture three

BIOL 533 7 Lecture Three Studying Pathogenic Organisms • Look at other, similar members of the same genus; for example: – M. smegnatis vs. – M. tuberculosis M. smegnatis is faster-growing; methods may be applicable to M. tuberculosis

Studying Pathogenic Organisms a5 Approaches for identifying virulence factor and proving its importance in causing disease Biochemical Genetic Immunological Best to combine approaches BIOL 533 Lecture three

BIOL 533 8 Lecture Three Studying Pathogenic Organisms • Approaches for identifying virulence factor and proving its importance in causing disease: – Biochemical – Genetic – Immunological • Best to combine approaches

Biochemical/Immunological Purify molecule and study in vitro Yields detailed information about Cofactors General physical properties BIOL 533 Lecture three

BIOL 533 9 Lecture Three Biochemical/Immunological • Purify molecule and study in vitro • Yields detailed information about – Cofactors – General physical properties

Biochemical/Immunological TWo limitations Molecule must be assayable: most applicable if know product and function Measurements on isolated molecules may not accurately reflect function in intact bacterium Prove function in vivo, have to take either genetic or immunological approach BIOL 533 Lecture three

BIOL 533 10 Lecture Three Biochemical/Immunological • Two limitations: – Molecule must be assayable; most applicable if know product and function – Measurements on isolated molecules may not accurately reflect function in intact bacterium • Prove function in vivo; have to take either genetic or immunological approach

Immunological Determine whether ab to bacterial product are protective in infected animals Possible problem Ab to bacterial surface molecules might prevent infection by opsonizing or enhancing complement action rather than inactivating virulence factor BIOL 533 Lecture three

BIOL 533 11 Lecture Three Immunological • Determine whether Ab to bacterial product are protective in infected animals • Possible problem: – Ab to bacterial surface molecules might prevent infection by opsonizing or enhancing complement action rather than inactivating virulence factor