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Pathogenic Microbiology. Promed ProMED Sign up for daily digest Some items from ProMED will be discussed.

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Presentation on theme: "Pathogenic Microbiology. Promed ProMED Sign up for daily digest Some items from ProMED will be discussed."— Presentation transcript:

1 Pathogenic Microbiology

2 Promed ProMED Sign up for daily digest Some items from ProMED will be discussed in class and qualify for exam questions

3 Agricultural revolution of Eurasia Led to the formation of cities The domestication of animals likely resulted in transmission of infectious diseases Cattle Anthrax Smallpox Swine Influenza Poultry Influenza Arboviruses Rodents (indirect) Arenaviruses Bubonic plague History of Infectious Diseases

4 The Plague of Athens (c. 430 B.C.) Thucydides described it as rapid onset, raging fever, extreme thirst, bloody tongue and throat, red skin followed by pustules and blisters Probably scarlet fever Killed about half of Athens’ population At the time Athens was engaged in war with Sparta The war should have been an easy victory for Athens Because of the societal impact, Athens became stagnant The war continued for 27 more years and Sparta won

5 The Plague of Galen (c. 165 B.C.) Galen was a Roman physician who described the disease Likely the first large outbreak of smallpox Corresponded with arrival of the Huns from east Asia Invasion of the Huns resulted in westward movement of Germanic peoples and encroachment upon Rome Roman soldiers on the eastern front were first to be infected and upon returning to Rome brought the disease with them History of Infectious Diseases

6 The Plague of Justinian By 500 A.D. the Roman Empire was seated in Constantinople (Byzantine Empire) Justinian I was Emperor and was battling the Goths and Vandals An outbreak of what resembles bubonic plague occurred that weakened the legion History of Infectious Diseases

7 I Samuel: “Then said they, What shall be the trespass offering which we shall return to him? They answered, Five golden emerods, and five golden mice, according to the number of the lords of the Philistines: for one plague was on you all, and on your lords.” Emerods = “tumors”

8 Three pandemics from 540 to 1666 The Justinian Plague (540-590) The Black Death (1346-61) The Great Plague of London (1665-1666) Bubonic plague (Yersinia pestis) Rat-flea-human infection cycle Each started in coastal cities and moved inland Those who cared for the sick were at no greater risk than those who did not Death rates were low at the beginning, but as high as 90% toward the end A higher incidence of pneumonic plague occurred at the end Agricultural production dropped, leading to mass starvation History of Infectious Diseases The Dance of Death by Hans Holbein, c. 1519

9 Smallpox Likely arose in India Probably a zoonotic agent from cattle Efficient human to human transmission Wherever Europeans explored, they took smallpox with them Indigenous populations usually had high fatality rates When Spaniards colonized Mexico the fatality rate was 100% for some villages Variolation - First immunization using cowpox pustules scarified into the skin Cross-reactive immune response Eradicated in the 1970s History of Infectious Diseases

10 Edward Jenner (1749-1823) performing the first vaccination against Smallpox in 1796, by Gaston Melingue The Cow Pock or the Wonderful Effects of the New Inoculation, byJames GillrayJames Gillray

11 Measles First described by Persians (c. 700 A.D.) Two week incubation Respiratory transmission Immunosuppressive Secondary bacterial infections 60% of deaths from pneumonia (pre- antibiotics) in small children In older children, death is frequently from neurological manifestations Measles is the next disease targeted for eradication (after smallpox and polio) History of Infectious Diseases

12 European Arrival, 19th Century Endemic Malaria History of Infectious Diseases European colonization of Africa

13 Colonization of the New World 1400s to 1600s Europeans migrated to the Americas They brought diseases that were absent in the Americas Smallpox Measles Influenza Typhus Yellow fever (slave trade) Europeans had evolved with most of these diseases, thus were genetically-prepared for them Native American populations were not It is evident that most of the 58 million Native American deaths were from European diseases The British used smallpox as a biological weapon History of Infectious Diseases

14 Infectious diseases have shaped, and will continue to shape, humanity Given the opportunity, any microbe can cause disease

15 Characteristics of infectious disease Communicable or contagious diseases are readily transmitted person to person (e.g., influenza, measles, pertussis) Other diseases are not contagious (including West Nile virus, anthrax) since they are not transmitted person to person Infection is also a function of quantity of microbes The infectious dose is expressed as ID 50 The ID 50 for a microbe is the number of bacteria or viruses needed to infect 50 of 100 people given the dose This number varies among pathogens (anthrax = 10,000) Review of Pathogenic Microbiology

16 Some Communicable Diseases DiseaseAgentRoute DiphtheriaCorynebacterium diphtheriaeRespiratory InfluenzaVarious influenza virusesRespiratory Bacterial Meningitis Neisseria meningitidis, Hemophilus influnezae type B Respiratory MeaslesRubeola virusRespiratory MumpsMumps virusRespiratory RubellaRubella virusRespiratory PertussisBordetella pertussisRespiratory PolioPolio virusFecal/Oral ChlamydiaChlamydia trachomatisSexual GonorrheaNeisseria gonorrhoeaeSexual HIVHIV-1, HIV-2Sexual SyphilisTreponema pallidumSexual Infectious hepatitis Various hepatitis virusesVarious

17 Review of Pathogenic Microbiology Pathogenic - the capacity to cause disease Acute pathology - symptoms are apparent Subacute pathology - symptoms are inapparent Pathogenic microbe - any microbe that can cause disease Nearly any microbe, given the opportunity, can cause disease Pathogenesis - the process by which pathology occurs Virulence factors are responsible for pathogenesis They are molecules encoded by genes that allow the microbe to compromise the host Usually toxins for prokaryotes The genes in a toxin pathway are often cluster together in pathogenicity islands Subversion of host cellular processes Usually immune modulators for viruses The immune response often contributes to pathogenesis

18 Pathogenicity The capacity for a microbe to cause disease Some microbes are primary pathogens and usually cause disease after colonization Others are opportunistic pathogens and cause disease only in conjunction with some other unusual event Immunocompromised status Chemotherapy HIV disease Congenital immunodeficiency Compromised normal flora Aggressive antibiotic therapy Clostridium difficile Review of Pathogenic Microbiology

19 Infection - usually parasitic colonization by a microbe Clinical manifestations Subclinical (apathogenic) - none apparent Clinical (pathogenic) - symptoms of disease Course of infection Primary - disease caused by the initial infection Secondary - because of the initial infection, another microbe can establish an infection Review of Pathogenic Microbiology

20 Distribution of the pathogen Most are localized to a specific tissue Others can be systemic Some localized infections can become systemic; often a poor prognostic indicator Microbes and their products in the blood Bacteremia - bacteria in blood Viremia - virus in the blood Toxemia - toxins in the blood Septicemia - life-threatening; bacteria replicating in the blood Review of Pathogenic Microbiology

21 Adherence Mediated by glycoproteins termed adhesins Typically have specificity for host cell surface proteins Colonization Replication of bacteria at the site of adherence Secretion of factors that impair the host response, such as proteases that cleave antibodies, rendering them nonfunctional Expression of iron-binding molecules, termed siderophores Biofilms (tissues and medical devices) Delivery of effector molecules into host cells Often virulence factors that damage the host cell Review of Pathogenic Microbiology


23 Course of Infection Incubation period - no symptoms Illness - phase of disease Convalescence - recovery from disease Some people can be carriers for some infectious agents (”Typhoid Mary”) Duration of Symptoms Acute - rapid onset, short duration Chronic - slow onset, long duration Latent - agent is never eliminated Recrudescence is the recurrence of a latent viral infection Review of Pathogenic Microbiology

24 Koch’s Postulates of Infectious Disease Etiology The microbe must be present in every instance of the disease The microbe must be isolated and cultured from a diseased animal Introduction of the microbe into a susceptible animal must result in the disease The microbe must be reisolated from the animal

25 Genetic Basis of Microbial Virulence Genomic DNA Plasmid DNA Bacteriophage (“phage”) DNA Transposons

26 Plasmid-Encoded Virulence Factors OrganismVirulence FactorBiological Function Enterotoxigenic E. coli Heat-labile and -stable enterotoxins Activation of adenylate guanylate cyclase in GI leading to diarrhea Extraintestinal E. coliHemolysinCytotoxin Shigella sp and enteroinvasive E. coli Gene products involved in invasion Induce internalization by intestinalepithelial cells Yersinia sp Adherence factors and gene products involved in invasion Attachment, invasion Bacillus anthracis Edema factor, lethal factor and protective antigen EF is an adenyl cyclase; LF is a metalloprotease that acts on cell signalling Staphylococcus aureus Exfoliative toxinCauses toxic epidermal necrolysis Clostridium tetaniTetanus neurotoxin Blocks release of inhibitory neurotransmitter, leading to muscle spasms

27 Phage-Encoded Virulence Factors OrganismVirulence FactorBiologic Function Corynebacterium diphtheriae Diphtheria toxinInhibition of eukaryotic protein synthesis Streptococcus pyogenes Erythogenic toxinRash of scarlet fever Clostridium botulinum Botulism neurotoxin Blocks synaptic acetylcholine release, which leads to flaccid paralysis Enterohemorrhagic E. coli Shiga-like toxinInhibition of eukaryotic protein synthesis Vibrio choleraeCholera toxin Stimulates adenylate cyclase in host cells

28 Molecular Postulates of Infectious Disease Etiology The virulence factor or gene(s) must be detected in pathogenic members of a species, but not nonpathogenic members Introduction of the gene(s) that encodes the virulence factor into a nonpathogen must convert the microbe into a pathogenic strain The gene(s) must be expressed when introduced into a susceptible animal Antibodies or immune cells (e.g., Tc cells) must protect the animal from the disease

29 Penetration of the skin Cuts, abrasions, or burns Vector (flea, mosquito) Penetration of the mucous membranes Directed uptake by cells Exploitation of antigen sampling by immune cells Dendritic cells Macrophages Breaching Anatomic Barriers

30 Toxins Background Greek toxikon “Bow poison” - poisons commonly applied to arrows used by Greek warriors Coined by Roux and Yersin Cell-free culture liquids of Corynebacterium diphtheriae killed animals when injected Many toxins are enzymes

31 Synthesis and release of toxins Highly complex Usually controlled by environmental stimuli Toxin expression pathways are often encoded in the same regulon that allows concurrent expression of pathogenicity islands during particular stages of infection Toxins

32 Host Damage Exotoxins Proteins secreted by various pathogenic bacteria Can be local or systemic Fatal in small amounts 1 gram of botulinum toxin is sufficient to kill the Earth’s human population Potent antigens, but exert their effect before antibodies can be synthesized A-B toxins - disrupt cellular pathways to the microbe’s advantage B subunit specifies ligand A subunit has enzymatic activity Membrane-damaging toxins - hemolysin disrupts RBC membranes Superantigens “trick” large numbers of helper T cells into producing inflammatory cytokines


34 Type III secretion systems Some microbes use this system to inject enzyme toxins directly into target cells; a molecular syringe

35 Endotoxins Endotoxins are lipopolysaccharides (LPS) Lipid A (toxic) Polysaccharide Normally found as outer cell membrane component of Gram - bacteria Bind to Toll-like receptors on phagocytic cells, which results in the release of tumor necrosis factor from the cells TNF causes capillary leakage and inflammation This can lead to hypotension and disseminated intravascular coagulation - aka, septic shock Host Damage


37 Toxins Classification Chemical Protein Lipid Lipopolysaccharide Cellular or tissue target of action Enterotoxins Neurotoxins Leukotoxins Mechanism of action Proteolytic toxins ADP-ribosylating toxins Adenylate cyclase toxins Deamidating toxins Classification Major biological effect Small G proteins Heterotrimeric G proteins Intracellular target molecule Enterotoxins Neurotoxins Leukotoxins

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