复旦大学：《医学微生物学 Medical Microbiology（MBBS）》课程讲义_理论课_Lecture4-pathogenesis

Normal human microbiota Pathogenesis of Bacterial Infection DiQu(瞿涤) MOH&MOE Key Lab of Medical Molecular Virology Shanghai Medical College, Fudan University 复旦大学基础医学院 医学分子病毒学教育部卫生部重点实验室 Chapter 10 Chapter 9

Normal Human Microbiota Pathogenesis of Bacterial Infection Shibo Jiang (姜世勃) MOH&MOE Key Lab of Medical Molecular Virology Shanghai Medical College, Fudan University 复旦大学上海医学院分子病毒学教育部/卫生部重点实验室 Di Qu (瞿涤) MOH&MOE Key Lab of Medical Molecular Virology Shanghai Medical College, Fudan University 复旦大学基础医学院 医学分子病毒学教育部/卫生部重点实验室 Chapter 10 Chapter 9

Key Words Pathogen Opportunistic pathogen Adhesion Normal microbiota Penetration Pathogenicity Invasiveness/spread Extra/intra cellular bacteria Virulence Exotoxin Opportunistic infection Nosocomial infection Toxoid Koch's postulates Endotoxin Carrier Transmission Compromised host Outbreak, Epidemic, Pandemic Bacterial biofilm

Key Words Adhesion Penetration Invasiveness/spread Extra/intra cellular bacteria Exotoxin Toxoid Endotoxin Carrier Compromised host Bacterial biofilm Pathogen Opportunistic pathogen Normal microbiota Pathogenicity Virulence Opportunistic infection Nosocomial infection Koch’s postulates Transmission Outbreak, Epidemic, Pandemic

Outline of the lecture Normal microbiota =normal flora Y Opportunistic infections Koch's postulates v Virulence of bacteria Invasive oxins -endotoxin exotoxin v Bacterial biofilms v Modes of infectious disease transmission Infections v Control of nosocomial infection

Outline of the lecture  Normal microbiota =Normal flora  Opportunistic infections  Koch's postulates  Virulence of bacteria Invasive Toxins – endotoxin exotoxin Bacterial biofilms Modes of infectious disease transmission Infections Control of Nosocomial Infection

Microbes and humans At lest two questions here Very few microbes are How to identify always pathogenic a pathogen? Many microbes are potentially pathogenic Under what condition? Opportunistic Most microbes are infection never pathogenic ()

Microbes and humans Very few microbes are always pathogenic Many microbes are potentially pathogenic Most microbes are never pathogenic Under what condition? -Opportunistic infection How to identify a pathogen? At lest two questions here

Microbes and human Normal flora =Normal microbiota(beneficial or ignored) GI track, skin, upper respiratory track Opportunistic bacteria(when host with underline problem) Pseudomonas aeruginosa: cystic fibrosis/burn Kaposis sarcoma(herpesvirus): AIDS E coll, Staphylococcus Virulent bacteria (actively cause disease) Mobile genetic elements pathogenic islands

Microbes and Human Normal flora =Normal microbiota (beneficial or ignored):  GI track, skin, upper respiratory track… Opportunistic bacteria (when host with underline problem):  Pseudomonas aeruginosa: cystic fibrosis/ burn  Kaposi’s sarcoma (herpesvirus): AIDS  E.coli，Staphylococcus Virulent bacteria (actively cause disease): Mobile genetic elements pathogenic islands

DIVERSITY IN THE HUMAN MICROBIOME The human Microbiome Project has examined bacteria on 242 lable 10-1 people. Some of the microbes living in and on the human body: Propionibacterium acnes lives on the skin and nose of Streptococcus dominates ost people the oral cavity Bacteroides is the most abundant genus in the gut of almost Staphylococcus healthy subjects epidermidis colonizes external body sites E. coli is present in the Lactobacillus gut of the majority of species are healthy subjects but at predominant very low abundance in the vagina SOURCE: Human Microbiome Project

Table 10-1

Copyright o The McGraw-Hill Companes lne. Permission required for ction or dsplay TABLE 13.1 Sites That Harbor a Normal Flora Sites of normal Skin and its contiguous mucous membranes Microbiota Upper respiratory tract Gastrointestinal tract (various parts Outer opening of urethra External genitalia Copyright o The McGeaw-Hill Companies, Ine. Permission required for reproduction or diply · Vagina TABLE 13.2 Sterile(Microbe-Free) Anatomical · External ear canal Sites and fluids External eye(lids, conjunctiva) All Internal Tissues and organs Heart and circulatory system Kidneys and bladder Lungs Brain and spinal cord Muscles Microbe-free sites Ovaries /testes Glands(pancreas, salivary, thyroid) Sinuses Middle and inner ear ab|e10-1 Internal eye Fluids Within an Organ or Tissue Blood Urine in kidneys, ureters, bladder Cerebrospinal fluid Saliva prior to entering the oral cavity Semen prior to entering th e urethra Amniotic fluid surrounding the embryo and fetus

Sites of Normal Microbiota Table 10-1 Microbe-free sites

● Extemal auditory Retroauricular O O Nare Occiput● Table 10-1 Normal ● Manubrium Bacterial Microbiota O Axillary vault dO Antecubital Gluteal O Differs in the different MAAN pliteal fossa O v location HYpothenar Plantar heel O web space O Inguinal crease UMbilicus O Toe web space □ Corynebacteriaceae Micrococcaceae Other actinobacteria Other firmicutes ● Sebaceous Moist O Dry C Butel Is, Morse SA M TA: Jawetz, Melnick, Adelberg's Micrebialogy,25thEdition:www.accessmedicine.co

Table 10-1 Normal Bacterial Microbiota Differs in the different location

Microbes and humans Disease can come about in several overlapping ways 1. Entirely adapted to the pathogenic way of life in humans, and never be part of the normal flora but may cause subclinical infection, e.g. M.tuberculosis 2. Part of the normal flora acquire extra virulence factors making them pathogenic, e.g. E. coll 3. Part of the normal flora can cause disease if they gain access to deep tissues by trauma, surgery, lines, e.g.s epidermIdIS 4. In immunocompromised patients many free-living bacteria and components of the normal flora can cause disease, especially if introduced into deep tissues, e.g Acinetobacter

Microbes and humans Disease can come about in several overlapping ways 1. Entirely adapted to the pathogenic way of life in humans, and never be part of the normal flora but may cause subclinical infection, e.g. M . tuberculosis 2. Part of the normal flora acquire extra virulence factors making them pathogenic, e.g. E. coli 3. Part of the normal flora can cause disease if they gain access to deep tissues by trauma, surgery, lines, e.g. S. epidermidis 4. In immunocompromised patients many free-living bacteria and components of the normal flora can cause disease, especially if introduced into deep tissues, e.g. Acinetobacter

Normal microbiota All body surfaces possess a rich normal bacterial flora especially the mouth, nasopharynx, gastrointestinal tract vagina, skin This can be a nuisance v contaminate specimens cause disease This is beneficial protect against infection by preventing pathogens colonising epithelial surfaces(colonisation resistance) v removal of the normal flora with antibiotics can cause superinfection, usually with resistant microbes Endogenous viruses reside in the human genome worries about similar pig viruses in xenografts

Normal microbiota • All body surfaces possess a rich normal bacterial flora, especially the mouth, nasopharynx, gastrointestinal tract, vagina, skin… – This can be a nuisance contaminate specimens cause disease – This is beneficial protect against infection by preventing pathogens colonising epithelial surfaces (colonisation resistance) removal of the normal flora with antibiotics can cause superinfection, usually with resistant microbes • Endogenous viruses reside in the human genome – worries about similar pig viruses in xenografts