Medical Microbiology Lecture 9 PDF

Medical Microbiology BS2002 Lecture 9 A/Prof Yann Boucher SCELSE, Public Health, NUS [email protected] 1  Pippi’s Pedigree + My Scientific Pedigree Carl Woese Norm Pace F...

Medical Microbiology BS2002 Lecture 9 A/Prof Yann Boucher SCELSE, Public Health, NUS [email protected] 1  Pippi’s Pedigree + My Scientific Pedigree Carl Woese Norm Pace Ford Doolittle Yann Boucher Dog owner Just shy of Nobel NAS member NAS member Father of new Father of Archaea Father of 16S Father of LGT Vibrio species Meet your Prof  Medical Microbiology Human body is a diverse environment – Specific niches – Most microbes are benign Application of ecological principles – Many interactions between human and normal microbial flora – Microbiota - microbes regularly found at a given anatomical site  Normal flora Microorganisms living on body surfaces of healthy individuals bacteria more cells than rells human ~1014 bacteria and archaea in fewer average adult (about 1013 human cells) bigger - , all Most in the gut (400 m2 surface) 2 – Skin (2m2) great sa – Mouth – Respiratory tract – Urogenital tract - not a problem when healthy sick/get but once you get Many normal flora opportunistic pathogens a they cut/imunocompromised can take up e , Commensalism or mutualism? opportunity infect to cause an & both benefit  teeth disrupts microbial biofilm brushing Mouth Microbes adhere to gums and teeth Not removed by brushing – Acid contributes to dental plaque, caries, gingivitis, and periodontal disease Oral cavity colonized by microorganisms from the surrounding environment within hours following birth 6  Sugar—fermented to lactic acid Bacteria colonize tooth surfaces by attaching to glycoproteins deposited by saliva Extensive growth of oral microbes results in a thick bacterial layer (dental plaque) biofilm microbes & I bottom of thick ~ Eventually, anaerobic species grow they undergo fermentat - : ↑ acid Produce high concentrations of acid causing poce cavities teeth is calcium (minerals) that decalcifies tooth enamel (dental acid 7 caries): Streptococcus mutans dissolve in & they & gives it holes & barteria in e holes can go to eat flesh  Gastrointestinal tract to throughI month to get in there microbes have get Stomach: most microbes killed by acidic conditions – some survive if pass through very quickly – some survive in food particles - fairly acidic still Small intestine: few organisms not much acid oxygen no , ~ Large intestine: largest microbial population of body (1013 to 1014 microbial cells) – Eliminated from body by peristalsis, desquamation, and movement of mucus – Replaced rapidly due to rapid doubling times 8 – Most microbes are anaerobes Bacteria associated with mucous membranes nice lining e is a mucus in G1 tract in e mucous some bacteria live if bacteria I can be a point of entry is a pathogen Mucous membranes are frequent sites of infection due to favorable environment for bacterial growth 9  bacteria can break down food into smaller units, I provide more energy , calorie intake (good/bad thing wood 10 influence , state , brain , etc. chemical signaling  Bacteroides Colonizes exfoliated host cells, food particles and sloughed mucus Rapidly eliminated if not attached Adheres to particles in the gut, not the gut itself Degrades complex carbohydrates along with methanogens to get energy 11  Bacteroides and obesity Human gut: 10-100 trillion bacteria – Bacteroides and Firmicutes are main microorganisms that break down food- polymers sugar – Obese people have less Bacteroides and more Firmicutes than slim people – Bacteroides populations increase as obese people lose weight Bacteria-free mice infected with microbial population from guts of obese mice become obese Microbes determine how many calories can be extracted and absorbed! 12  Why? Firmicutes have numerous enzymes that break down “indigestible” carbohydrates Additional nutrients absorbed by intestine Leads to higher caloric intake from exact same food 13  Innate Resistance to Infection Nonspecific barriers prevent colonization of the host by most pathogens ~ biggest protecte Lack of defenses results in susceptibility to infection and colonization by pathogens 14 Deaths by cause, circa 2017 parasite 16  How do communicable disease happen ? Transmission routes Person-to-person – Airborne – Direct contact – Sexually transmitted mosquitos malaria sats transmitting diseases ~ dengue , , , Zoonotic and vectorborne tetanus toxin Soilborne ~ Salmonella Cholera ~ , Waterborne salmonella Foodborne -  Terms of Pathogenicity Attenuation ~ used for vaccines – The decrease or loss of virulence Toxicity – Ability of an organism to cause disease through making a toxin that inhibits host cell function or kills host cells – Toxins can travel to sites within host that are not inhabited by the pathogen & can pass through even I blood-brain barrier Invasiveness – Ability of pathogen to grow in host tissue at densities that inhibit host function – Cause damage without producing a toxin Many pathogens use combination of toxins, invasiveness, and virulence factors to enhance 18 pathogenicity  process of pathogenesis Pathogenesis Pathogens use various strategies to establish virulence 19  Adherence of pathogen Pathogen gains access Vibrio cholerae on to host tissues and intestinal villi to stick is using multiplies before damage way one to capsules , sticky sugars , cells epithelial can be done stick to Infectious bacteria and viruses often adhere specifically to epithelial cells E. coli contacting villi via capsule – Interactions between surfaces of the pathogen and surfaces of host cell 20  other many ways of adverance these are all diff types of virulence factors as they help i pathogenicity - one of components F membrane that allows it to cells - stick to e can also stick to things 21  Invasion Starts at the site of adherence May spread throughout the host via the blood circulatory or lymphatic systems basteria in can lead to Sepsis Availability of nutrients most important in affecting pathogen growth Pathogens may grow locally at site of invasion or spread throughout the body 22  Virulence Estimated from experimental studies of LD50 (lethal dose50): dose of agent that kills 50% of animals in test group 100 90 80 Response (%) 70 60 smaller E LD50 , i more virulent 50 40 30 20 10 LD50 = 17 bacteria x 100 0 10 20 30 40 50 23 Dose (# bacteria x 100)  Virulence Real determinate of virulence Highly virulent pathogens: little difference in # diff in no If diff in no of cells of cells between & (Dcor cells betw betw LD50 LD So & LD100 is greater => less virulent LD50 and LD100 is small very virulent > very - 24  Virulence Factors Enzymes that: – Enhance virulence by breaking down or altering host tissue to provide access to nutrients Hyaluronidase breaks down hyaluronic acid that cements animal cells together make space for bacteria to enter – Protect pathogen by interfering with normal host defense mechanisms Coagulase allows bacteria to be coated with fibrin < bacteria protect against immune system but can also 25 cause blood clots  pieces of pot that more befor bacteria - mostly carried by mobile genetic element ~ Lacquired by exchange of material betw bacteria I and piece of DNA that moves using to jump and genome (bacteriophage) transposase 26  allowing survival & invasi of body ~ Virulence Factors: Salmonella small molecules that grab iron injects toxi on ~ ~ which is a nutrient for bacteria & cells lose water structural parts that ~ are toxic to e body inhibits pragocytes of : immune system - ~get to site of infected evade immure system 27  Summary: Salmonella protects I basteria all ~ LPS: Gram negative cell wall; outer membrane structure - – Endotoxin: frequent in food-borne pathogens itself is toxic – O-specific polysaccharide Iron uptake – Siderophore: to aid growth Virulence plasmid: only in pathogenic strains Fimbriae: adherence Enterotoxin: exotoxin that affects small intestine & create more friendly ear* for bacteria 28  Exotoxins Proteins released from pathogenic organism as it grows Three categories – Cytolytic toxins – AB toxins – Superantigen toxins 29  Cytolytic toxins Work by degrading cytoplasmic membrane integrity Causing host cell lysis and death blood -agai plates if there is a Hemolysins zore of meaning clearance L break bacteria can down RB e degrada & break RB2 them open , e there is toxin 30 cyfolytic called nemolysing Example: Staphylococcal α toxin cell makes a pove in its a P that assembles in i memb of host all , a allowing things to in go out this messes osmotic balance , 31  AB toxins Consist of A and B subunits Work by binding to host cell receptor (B attachment subunit) and transfer a damaging agent (A - allows & penetrate of toxic subunit) across the cell membrane & effector actual 32  Diphtheria toxin Catalyzes ADP-ribosylation of elongation factor 2 (EF-2) and prevents transfer of amino acids to growing peptide chain in ribosome cell cannot make P & dies P birds to receptor - ↑ helptranspoa emb ~ 33  anaerobic bac -. Botulism (Clostridium I can grow inside i can botulinum) can is bumpy in> Ibacteria - can is growing bart &. polce gascan makes I bumpy 34  offeis Botulinum Toxin is ners Blocks release of acetylcholine to muscle tissue resulting in permanent relaxed state 35  100 90 Infant 80 botulism 70 Outbreak caused by 60 chili sauce, Texas Cases 50 Outbreak caused Outbreaks caused by by baked 40 fermented fish/seafood potatoes, Texas products, Alaska 30 20 Foodborne 10 botulism 1985 1990 1995 2000 2005 Year 36  provoke an overdrive immune system response Superantigen toxins ~ ~ does e damage Stimulate large numbers of immune cells I on body Result in extensive inflammation and tissue damage 37  Endotoxins Lipopolysaccharide portion of cell wall of certain gram-negative Bacteria is a toxin when solubilized Generally less toxic than exotoxins 38 Campylobacter jejuni endotoxins Food-borne pathogen, primarily from poultry Most common cause of bacterial gastroenteritis in the world 1 in 1000 people develop Guillain-Barré Syndrome – Paralytic disorder 39  C. jejuni LPS components mimic human gangliosides (host sugars) & in nervous system Immune system makes antibodies against bacterial sugar, but also attacks own sugars 40 Airborne Pathogens Aerosols are important for person-to-person transmission of many infectious diseases. Most pathogens survive poorly in air; thus, they are effectively transmitted only over short distances. Respiratory infections Different pathogens characteristically colonize the respiratory tract at different levels. The upper and lower respiratory tracts offer different environments (temperature, air flow, pH, etc.) and favor different microbes.  Tuberculosis Tuberculosis is caused by Mycobacterium tuberculosis. Hansen’s disease (leprosy) is caused by Mycobacterium leprae. All mycobacteria are acid- fast because of the waxy mycolic acid content of their cell walls.  Tuberculosis worldwide infectious disease of humans Incidence is increasing. M. tuberculosis is transmitted by airborne droplets. Cell-mediated immunity plays a critical role in preventing active disease after infection. classified as a primary infection (initial infection) or postprimary infection (reinfection)  Tuberculosis Spread of tuberculosis is prevented by hospitalization of patients in negative-pressure rooms use of face masks for healthcare workers Treatment Antimicrobial therapy with isoniazid or rifampin Treatment usually requires a nine-month regimen. affects the synthesis of mycolic acid in mycobacteria Directly observed therapy (DOT) is popular in some areas, to assure compliance with the doctor’s orders and reduce the risk of antibiotic resistance.  Tuberculosis What is multidrug-resistant tuberculosis (MDR TB)? Multidrug-resistant TB (MDR TB) is caused by an organism that is resistant to at least isoniazid and rifampin, the two most potent TB drugs. These drugs are used to treat all persons with TB disease. What is extensively drug resistant tuberculosis (XDR TB)? Extensively drug resistant TB (XDR TB) Predicted TB prevalence from 2019 is a rare type of MDR TB that is resistant to 2050 under current TB control to isoniazid and rifampin, plus any conditions. DS-TB+, bacteriologically fluoroquinolone and at least one of three injectable second-line drugs (i.e., confirmed drug-susceptible TB; MDR- amikacin, kanamycin, or capreomycin). TB, multidrug-resistant tuberculosis Other treatment options much less (China) effective.  Risk Factors for Infection Compromised Host: one or more resistance mechanisms are inactive and probability of infection is increased Age: factor for determining susceptibility to infectious diseases – Very young and very old individuals are more susceptible Stress: predisposes healthy individuals to disease Diet and lifestyle choices (e.g. smoking) Genetic conditions can compromise a host 47  Specific immunity Complex, multi-pathway systems – Innate immunity (phagocytes) – T-cell immunity – Antibody-mediated immunity Once an organism is recognized, person is immune – Immune memory The immune system https://www.youtube.com/watch?v=lXfEK8 49 G8CUI  Immunization Inoculation with attenuated or killed pathogens or chemically modified exotoxin—vaccination pre-empt development of ~ immune get sick system 34 you Immune system recognizes specific antigens—can mutate depends I on bacteria – Why we need new flu vaccine each year – More likely to happen with viral than bacterial diseases 50  * not I in of people context getting immunity after getting infected Herd immunity in a context of vaccinate it , protectse vulnerable that cannot are not vaccinated , need (vaccinated people) disease cannot be infectious disease vaccinated - blocks I transmiss betw them a transmitted through them (yellow) - they don't get virus as their confact is alr vaccinated no herd immunity 51  Disease Eradication ? - destroyina g can but - be Polio and Measles eradicated vaccinate program stopped bet of Covid-19 only disease eradicated is pletely smallpox 52 53 54 55 56