Human-Microbe Interactions

BIOL 310 MicrobiologyMicrobial Interactions with HumansNormal microbial floraMicroorganisms that are usually found associated with healthy body tissueColonizationGrowth of a microorganism after it has gained access to host tissuesOverviewHostAn organism that harbors a parasiteParasiteAn organism that grows in or on a host and causes diseasePathogenAn organism, usually a microorganism, that causes diseaseOutcome of host-parasite relationship depends on:Resistance or susceptibility of host to parasitePathogenicity ability of a parasite to inflict damage on the hostThe environmentOpportunistic pathogenAn organism that causes disease only in the absence of normal host resistanceVirulenceQuantitative measure of pathogenicityCell number that elicits disease in a host within a given time periodPathogensInfectionAny situation in which a microorganism is established and growing in a host, whether or not the host is harmedDiseaseDamage or injury to the host that impairs host functionInfection and DiseaseAnimal hosts provide favorable environments for growth of microorganismsRich in organic nutrients and growth factorsProvide conditions of controlled pH, osmotic pressure, and temperatureEach region/organ a selective environmentRelative dryness of skin favors Staphylococcus aureus High O2 of lungs favors Mycobacterium tuberculosisLow O2 of intestine favors Clostridium genusHost-Parasite Interactions

Infection starts at mucous membranesLine the urogenital, respiratory, and gastrointestinal tractsConsist of single or multiple layers of epithelial cells frequently coated with a protective layer of viscous soluble glycoproteins called mucusIf microorganisms adhere to epithelial cell as a result of cell-cell recognition, infection occursThe Infection Process

Figure 28.1 (Madigan et al. 2009)Beneficial Microbial Interactions with Humans

Average adult has 2 m2 of skin surface Varies in chemical composition and moisture contentMost organisms associated withapocrine (sweat) gland secretionsUnderarm, genital regions, nipples, and the umbilicusDo not become fully functional until pubertyNormal Microbial Flora of the SkinFigure 28.2 (Madigan et al. 2009)Normal flora of skin (bacteria, fungi, yeasts) are either transients or residentsResidents are able to grow on skin, not merely survive like transient organisms

Most common and stable resident microorganisms are gram-positive BacteriaSpecies of Staphylococcus and StreptococcusSpecies of CorynebacteriumPropionibacterium acnesSmall numbers of gram-negative BacteriaEscherichia and other intestinal organisms constantly inoculated onto skin via fecal contaminationAcinetobacter (non-fecal)***Inability to compete with gram-positive BacteriaWhat influences microflora composition on skin?WeatherAgePersonal hygiene

Normal Microbial Flora of the SkinSaliva is not an especially good growth medium for microorganismsNutrients in low concentrationAntibacterial substancesLysozyme cleaves glycosidic bonds in peptidoglycanLactoperoxidase enzyme that kills bacteria

Structure of a toothEnamel mineral matrix of calcium phosphate crystalsDentin and pulp living toot tissueNormal Microbial Flora of the Oral Cavity

Figure 28.3 (Madigan et al. 2009)ColonizationAttachment of single bacterial cellsAcidic glycoproteins from saliva form a thin organic film several micrometers thick attachment siteStreptococcus speciesFormation of plaqueThick bacterial layer resulting from colonization of glycoprotein filmAs plaque continues to form, filamentous anaerobes begin to growNormal Microbial Flora of the Oral CavityFigure 28.4 (Madigan et al. 2009)

Bacteria in the mouth differ as humans age What predominates and why?In first year of life (no teeth present) aerotolerant anaerobes (i.e. streptococci and lactobacilli) predominateWhen teeth appear, balance of microflora shifts toward anaerobesNormal Microbial Flora of the Oral CavityAs plaque accumulates, microflora produce high concentrations of organic acids that cause decalcificationDiets high in sucrose promote dental cariesLactic acid bacteria (Streptococcus sobrinus and mutans) ferment sugar to lactic acidCalcium phosphate is dissolved followed by proteolysis of supporting matrix allowing bacteria to penetrate further into matrixIncorporation of fluoride into calcium phosphate crystal tooth matrix increases resistance to acid decalcificationMicroorganisms in the mouth can also cause gingivitisDental Caries

Figure 28.5 (Madigan et al. 2009)Normal Microbial Flora of the Gastrointestinal Tract

Figure 28.8 (Madigan et al. 2009)Gastrointestinal tract consists of stomach, small intestine, and large intestineResponsible for:Digestion of foodAbsorption of nutrientsProduction of nutrients by indigenous microfloraOverall, there is about 1013 to 1014 microbial cells present in GI tractNormal Microbial Flora of the Gastrointestinal Tract

Bacteria make up one-third the weight of fecal matterTotal number of bacterial cells shed per day is on order of 1013Passage of material through entire GI tract takes about 24 hours

Antibiotics inhibit growth not only of pathogens, but also normal microfloraCauses diarrheaAllows opportunistic pathogens to establish in GI tractProbiotics help to reestablish normal microfloraNormal Microbial Flora of the Gastrointestinal TractRespiratory tractUpper respiratory tractNasopharynx, oral cavity, larynx, and pharynxStaphylococci, streptococci, diptheroid bacilli, gram-negative cocciLowerTrachea, bronchi, and lungsNo resident microflora

Urogenital tractBladderSterileUrethraColonized by facultative aerobic gram-negative rods and cocci (E. coli, Proteus mirabilis)Normal Microbial Flora of Other Body RegionsHarmful Microbial Interactions with HumansPathogenesisThe ability of microorganisms to cause diseaseStepsExposure to pathogenAdherence to host cellInvasionColonizationGrowthResult of unchecked growthToxicityInvasiveness***Both lead to host cell damageEntry of the Pathogen into the Host

Figure 28.12 (Madigan et al. 2009)Ability of a pathogen to cause diseaseExperimental studies of LD50 Dose of agent that kills 50% of animals/cells in test groupLD50 for Streptococcus difficult to determine because so few cells required to kill 100% of populationLD50 for Salmonella between 103 and 104 cellsAttenuationReduction or loss of virulence due to maintenance in labAttenuated strains are used for production of vaccines, especially viral vaccinesMeasuring Virulence

Figure 28.16 (Madigan et al. 2009)ToxicityThe ability of an organism to cause disease by means of a preformed toxin that inhibits cell function or kills host cellse.g. Clostridium tetani produces tetanus toxin which initiates irreversible muscle contraction

InvasivenessThe ability of a pathogen to grow in host tissue in such large numbers that it inhibits host functione.g. Streptococcus pneumoniae produces polysaccharide capsule that prevents the phagocytosis of pathogenic strains, defeating host defense mechanismToxicity and InvasivenessVirulence in Salmonella

Figure 28.17 (Madigan et al. 2009)Virulence factorsPathogen-produced proteins aiding in establishment and maintenance of diseaseEnhance pathogen colonization and growthe.g. streptococci, staphylococci and certain clostridia produce hyaluronidaseEnzyme that breaks down a polysaccharide functioning as intercellular cement, allowing spread from initial site of infectionVirulence FactorsExotoxinCytolytic toxinAB toxinTwo covalently bonded subunits; B generally binds to cell surface receptor; A transferred across membraneSuperantigen toxinStimulate large numbers of immune cells, resulting in extensive inflammation and tissue damageDiptheria toxinTetanus and botulinum toxinsEnterotoxinCholera toxinEndotoxin

ToxinsExotoxinProteins released from pathogen cell as it growsCytolytic toxinsProteins that damage the host cytoplasmic membrane causing cell lysis and deathe.g. Hemolysins detected by growth on blood agarExotoxins

Figure 28.18 (Madigan et al. 2009)ExotoxinProteins released from pathogen cell as it growsAB toxinInhibit protein synthesise.g. Diphtheria toxin, produced by Corynebacterium diptheriaeExotoxins

Figure 28.20 (Madigan et al. 2009)ExotoxinProteins released from pathogen cell as it growsAB toxine.g. Botulinum toxin, produced by Clostridium botulinum

Figure 28.21 (Madigan et al. 2009)ExotoxinsExotoxinProteins released from pathogen cell as it growsAB toxine.g. Tetanus toxin, produced by Clostridium tetaniFigure 28.22 (Madigan et al. 2009)Exotoxins

EnterotoxinExotoxins whose activity affects the small intestineCholera toxin, produced by Vibrio choleraeEnterotoxin

Figure 28.23 (Madigan et al. 2009)Lipopolysaccharides produced by gram-negative Bacteria as part of the outer layer of their cell wallBound to cell wall and only released when cells are lysedFound in E. coli, Shigella, and SalmonellaEndotoxinsRisk factors for infectionAgeStress and dietCompromised hostInnate ResistanceNatural host resistanceTissue specificityIf exposure site is not compatible with nutritional and metabolic needs of pathogen, no colonizationPhysical and chemical barriersSkin and mucosal tissues

Host Factors in InfectionInnate Resistance to Infection

Figure 28.25 (Madigan et al. 2009)