MICROB 2300 1nd Edition Lecture 3 Outline of Current Lecture I. Microbial Pathogenesis 2a. Summary of Part 1b. Reservoirs of Infectioni. Animal Reservoirsii. Human Carriersiii. Nonliving Reservoirsc. Stages of Bacterial Pathogenesisd. Modes of Transmissione. Virulence Determinantsf. Exotoxinsg. Exceptions to Koch’s Postulatesh. Extent of Host Involvementi. EpidemiologyII. The Human Microbiomea. Microbiomeb. rRNAc. Studying Human Microbiomed. Relevancee. Weight and Microbiotaf. Antibiotics and MicrobiotaCurrent LectureMicrobial Pathogenesis ii Mike Baldwin [email protected] of part i• Human body is colonized by mutualistic and commensal microorganisms  NORMAL MICROBIOTA• Normal microbiota have low/moderate potential to cause disease  OPPORTUNISTIC PATHOGENSThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.• PRIMARY PATHOGENS have a high potential to cause diseaseSummary of part i• PATHOGENICITY: The ability of a microorganism to cause disease • VIRULENCE: The relative ability of a microorganism to cause disease in a specific host• Pathogenicity results from the expression of VIRULENCE FACTORSReservoirs of InfectionMost pathogens cannot survive long outside of their hostSites where pathogens are maintained as sources of infection are termed reservoirs 3 types of reservoirs:• Animal reservoir• Human carriers• Nonliving reservoirAnimal ReservoirsZoonoses: diseases that are naturally spread from their usual animal host to humansAnimal ReservoirsZoonoses: diseases that are naturally spread from their usual animal host to humansHuman CarriersInfected individuals who are asymptomatic but infective to othersNonliving ReservoirsSoil, water and food can be reservoirs of infection• Presence of microorganisms is often due to contamination by feces or urineStages of Bacterial PathogenesisTransmissionPenetration of the barrierAdherenceProliferation  colonizationClinical manifestations Host responseRecovery or death Modes of TransmissionModes of TransmissionPortals of Entry A Portal of Entry is the route a pathogen takes to enter a hostSome Pathogens that Cross the PlacentaPortals of Exit Evasion of the Host Immune SystemCapsule Antigenic mimicryMutationPhagosome escape Prevention of phagolysosomal fusionPrevention of phagolysosomal acidificationVirulence Determinants• Surface Virulence Factors• Capsules  Immune evasion• Pili  Adherence to target cells • Endotoxin• Component of bacterial membrane  inflammatory response• Exotoxins• Tissue damage  nutrient release• Dissemination to new hosts• Immune evasion Surface Virulence FactorsExotoxinsExceptions to Koch’s PostulatesSome pathogens can’t be cultured in the laboratorySome diseases are caused by a combination of pathogens Ethical considerations prevent applying Koch’s postulates to pathogens that require a human hostExtent of Host Involvement Localized:• Impetigo• Ear infection• SinusitisSystemic: • Bacteremia• Sepsis• Septic Shock• Toxic ShockEpidemiologyStudy of where and when diseases occur and how they are transmitted within populationsTrack occurrence of diseases using two measures• Incidence- number of new cases in a given area during a given period of time• Prevalence- number of total cases (new and pre-existing) in a given area during a given period of timeNosocomial InfectionsInfections acquired while in a health care facilityTypes of nosocomial infections• Exogenous: pathogen acquired from the health care environment• Endogenous: pathogen arise from normal microbiota due to factors within the health care setting• Iatrogenic:- results from modern medical proceduresControl of Nosocomial InfectionsInvolves precautions designed to reduce the factors that result in diseaseUniversal Precautions instituted by the CDC to limit exposure to pathogensHand washing is the most effective way to reduce nosocomial infectionsThe Human MicrobiomeRole in Infection and Human DiseaseAugust 28, 2014Mark McIntosh, [email protected]?The totality of microbes, including their genetic content (genomes), in a given environment.All plants and animals live in close association with microbial organisms. We usually consider the microbial world however in the context of disease states and a relatively small number of symbiotic case studies. But - Organisms do not live in isolation, but have evolved in the context of complex communities. Microbial Genomics and the Human MicrobiomeDistribution of Human MicrobiotaMicrobial Community Composition at Different Body LocationsHow do you generate this level of information about microbial niche populations (in any environment)?Remember, most organisms have never been cultured in the laboratory!!rRNA – The Common Denominator in All Microbial GenomesIdeal Substrate for Phylotyping at the Organism LevelMost organisms (>90%) cannot be cultivated under normal laboratory conditionsDNA sequence analysis of individual organisms or populations16S r RNA for phylogeny cataloguingFunctional cataloguing of enzymes, cell structuresHigh throughput DNA sequencing strategiesMassively parallel amplification of DNA targets How Do You Begin to Study the Human Microbiome?Next Generation DNA Sequencers capable of generating 2-20 Gigabases of sequence per runA Gigabase = 1 billion bases of DNA sequenceTypical bacterium = 4-5 Megabases of DNAHuman genome = 3 billion bases MetagenomicsAnalysis of all DNA sequences within a particular environment (gut, nasopharynx, urogenital tract, environment, etc.)Bacterial speciation within environment based on conserved DNA sequences (rRNA, conserved housekeeping genes)Next Generation TechnologiesWhat do we do with these metagenomic datasets?What is the “Normal” Human Gut Flora?Majority of bacteria associated belong to the Firmicutes and Bacteroidetes – constitute >90% of the known phylogenetic categories and dominate the distal gut microbiota; >80% represent sequences from species that have not been cultivatedSubstantial diversity of the gut microbiome between healthy individuals – especially marked among infants but converges to more similar phyla later in lifeFirmicutes95% are Clostridial speciesAlso Lactobacillus, Mycoplasma, Bacillus and many butyrate-producersFunction in maintenance and protection of the normal intestinal epitheliumBacteroideteshighly variable