1. 1 Applied Microbiology 8 th lecture: Chapter 13

2. 2 Microbes that engage in mutual or commensal associations - normal (resident) flora, indigenous flora, microbiota Microbes that engage in mutual or commensal associations - normal (resident) flora, indigenous flora, microbiota Infection- a condition in which pathogenic microbes penetrate host defenses, enter tissues and multiply Infection- a condition in which pathogenic microbes penetrate host defenses, enter tissues and multiply Disease – any deviation from health, disruption of a tissue or organ Disease – any deviation from health, disruption of a tissue or organ Caused by microbes or their products – infectious disease Caused by microbes or their products – infectious disease Microbe-Human Interactions Contact, Colonization, Infection, Disease

3. 3 Microbe-Human Interactions Contact, Colonization, Infection, Disease

4. 4 Microbe-Human Interactions Resident Flora: The human as a habitat Includes bacteria, fungi, protozoa, viruses and arthropods Includes bacteria, fungi, protozoa, viruses and arthropods Most areas of the body in contact with the outside environment harbor resident microbes; large intestine has the highest numbers of bacteria. Most areas of the body in contact with the outside environment harbor resident microbes; large intestine has the highest numbers of bacteria. Internal organs and tissues and fluids are microbe-free. Internal organs and tissues and fluids are microbe-free. Bacterial flora benefit host by preventing overgrowth of harmful microbes – microbial antagonism. Bacterial flora benefit host by preventing overgrowth of harmful microbes – microbial antagonism.

5. 5 Microbe-Human Interactions Resident Flora: The human as a habitat

6. 6 Microbe-Human Interactions Initial Colonization of the Newborn Uterus and contents are normally sterile and remain so until just before birth. Uterus and contents are normally sterile and remain so until just before birth. Breaking of fetal membrane exposes the infant; all subsequent handling and feeding continue to introduce what will be normal flora. Breaking of fetal membrane exposes the infant; all subsequent handling and feeding continue to introduce what will be normal flora. Resident Flora: The human as a habitat Within 8-10 hours after birth -> baby gets colonized by bacteria

7. 7 Microbe-Human Interactions Flora of specific regions

8. 8 Microbe-Human Interactions Flora of specific regions Flora indicated by yellow color

9. 9 Microbe-Human Interactions Life without Flora

10. 10 Microbe-Human Interactions Major Factors in the Development of an Infection True pathogens – capable of causing disease in healthy persons with normal immune defenses True pathogens – capable of causing disease in healthy persons with normal immune defenses influenza virus, plague bacillus, malarial protozoaninfluenza virus, plague bacillus, malarial protozoan Opportunistic pathogens – cause disease when the host’s defenses are compromised or when they grow in part of the body that is not natural to them Opportunistic pathogens – cause disease when the host’s defenses are compromised or when they grow in part of the body that is not natural to them Pseudomonas sp & Candida albicansPseudomonas sp & Candida albicans Severity of the disease depends on the virulence of the pathogen; characteristic or structure that contributes to the ability of a microbe to cause disease is a virulence factor (Biosafety levels). Severity of the disease depends on the virulence of the pathogen; characteristic or structure that contributes to the ability of a microbe to cause disease is a virulence factor (Biosafety levels).

11. 11 Microbe-Human Interactions Major Factors in the Development of an Infection

12. 12 Microbe-Human Interactions Major Factors in the Development of an Infection

13. 13 Microbe-Human Interactions Major Factors in the Development of an Infection Level 4 facilities

14. 14 Microbe-Human Interactions Major Factors in the Development of an Infection Portals of entry – characteristic route a microbe follows to enter the tissues of the body Portals of entry – characteristic route a microbe follows to enter the tissues of the body skin - nicks, abrasions, punctures, incisionsskin - nicks, abrasions, punctures, incisions gastrointestinal tract – food, drink, and other ingested materialsgastrointestinal tract – food, drink, and other ingested materials respiratory tract – oral and nasal cavitiesrespiratory tract – oral and nasal cavities urogenital tract – sexual, displaced organismsurogenital tract – sexual, displaced organisms TransplacentalTransplacental Exogenous agents originate from source outside the body. Exogenous agents originate from source outside the body. Endogenous agents already exist on or in the body (normal flora). Endogenous agents already exist on or in the body (normal flora).

15. 15 Microbe-Human Interactions Requirement for an Infectious Dose (ID) Minimum number of microbes required for infection to proceed Minimum number of microbes required for infection to proceed Microbes with small IDs have greater virulence. Microbes with small IDs have greater virulence. Lack of ID will not result in infection. Lack of ID will not result in infection. Major Factors in the Development of an Infection

16. 16 Microbe-Human Interactions Major Factors in the Development of an Infection Adhesion – microbes gain a stable foothold at the portal of entry; dependent on binding between specific molecules on host and pathogen Adhesion – microbes gain a stable foothold at the portal of entry; dependent on binding between specific molecules on host and pathogen fimbraefimbrae flagellaflagella adhesive slimes or capsulesadhesive slimes or capsules ciliacilia suckerssuckers hookshooks barbsbarbs

17. 17 Microbe-Human Interactions Attaching to the Host Major Factors in the Development of an Infection

18. 18 Microbe-Human Interactions Surviving Host Defenses Initial response of host defenses comes from phagocytes. Initial response of host defenses comes from phagocytes. Antiphagocytic factors – used to avoid phagocytosis Antiphagocytic factors – used to avoid phagocytosis Species of Staphylococcus and Streptococcus produce leukocidins, toxic to white blood cells. Species of Staphylococcus and Streptococcus produce leukocidins, toxic to white blood cells. Slime layer or capsule – makes phagocytosis difficult Slime layer or capsule – makes phagocytosis difficult Ability to survive intracellular phagocytosis Ability to survive intracellular phagocytosis Major Factors in the Development of an Infection

19. 19 Microbe-Human Interactions Causing Disease Virulence factors – traits used to invade and establish themselves in the host, also determine the degree of tissue damage that occurs – severity of disease Virulence factors – traits used to invade and establish themselves in the host, also determine the degree of tissue damage that occurs – severity of disease Exoenzymes – digest epithelial tissues and permit invasion of pathogens Exoenzymes – digest epithelial tissues and permit invasion of pathogens Toxigenicity – capacity to produce toxins ( at the site of multiplication Toxigenicity – capacity to produce toxins (Toxin: substance that is toxic to other cells) at the site of multiplication endotoxins – of Gram-negative bacteriaendotoxins – of Gram-negative bacteria exotoxins – proteins secreted by Gram-positive and Gram-negative bacteriaexotoxins – proteins secreted by Gram-positive and Gram-negative bacteria Antiphagocytic factors – help them to kill or avoid phagocytes; remain an irritant to host defenses Antiphagocytic factors – help them to kill or avoid phagocytes; remain an irritant to host defenses Major Factors in the Development of an Infection

20. 20 Microbe-Human Interactions Causing Disease - Toxins Major Factors in the Development of an Infection Secreted toxins Released after lysis

21. 21 Microbe-Human Interactions Causing Disease - Toxins Major Factors in the Development of an Infection A-B toxin of Corynebacterium diphtheriae Other toxins: - Toxin of Clostridium botulinum -> prevents transmission of nerve- muscle stimuli - Pertussis toxin -> inactivates respiratory cilia - Cholera toxin -> supports extreme amounts of salt and water loss from intestinal cells

22. 22 Microbe-Human Interactions The Process of Infection and Disease 4 distinct stages of clinical infections: 4 distinct stages of clinical infections: incubation period - time from initial contact with the infectious agent to the appearance of first symptoms; agent is multiplying but damage is insufficient to cause symptoms; several hours to several yearsincubation period - time from initial contact with the infectious agent to the appearance of first symptoms; agent is multiplying but damage is insufficient to cause symptoms; several hours to several years prodromal stage – vague feelings of discomfort; nonspecific complaintsprodromal stage – vague feelings of discomfort; nonspecific complaints period of invasion – multiplies at high levels, becomes well established; more specific signs and symptomsperiod of invasion – multiplies at high levels, becomes well established; more specific signs and symptoms convalescent period – as person begins to respond to the infection, symptoms declineconvalescent period – as person begins to respond to the infection, symptoms decline

23. 23 Microbe-Human Interactions Patterns of infection: Localized infection– microbes enters body and remains confined to a specific tissue Localized infection– microbes enters body and remains confined to a specific tissue Systemic infection– infection spreads to several sites and tissue fluids usually in the bloodstream Systemic infection– infection spreads to several sites and tissue fluids usually in the bloodstream Focal infection– when infectious agent breaks loose from a local infection and is carried to other tissues Focal infection– when infectious agent breaks loose from a local infection and is carried to other tissues Mixed infection – several microbes grow simultaneously at the infection site - polymicrobial Mixed infection – several microbes grow simultaneously at the infection site - polymicrobial Primary infection – initial infection Primary infection – initial infection Secondary infection – another infection by a different microbe Secondary infection – another infection by a different microbe Acute infection – comes on rapidly, with severe but short-lived effects Acute infection – comes on rapidly, with severe but short-lived effects Chronic infections –progress and persist over a long period of time Chronic infections –progress and persist over a long period of time Major Factors in the Development of an Infection

24. 24 Microbe-Human Interactions Major Factors in the Development of an Infection

25. 25 Microbe-Human Interactions Signs and Symptoms Sign – objective evidence of disease as noted by an observer Sign – objective evidence of disease as noted by an observer fever, septicemia, chest sounds, rash, leukocytosis, antibodiesfever, septicemia, chest sounds, rash, leukocytosis, antibodies Symptom – subjective evidence of disease as sensed by the patient Symptom – subjective evidence of disease as sensed by the patient chills, pain, ache, nausea, itching, headache. fatiguechills, pain, ache, nausea, itching, headache. fatigue Major Factors in the Development of an Infection

26. 26 Microbe-Human Interactions Signs and Symptoms of Inflammation Earliest symptoms of disease as a result of the activation of the body defenses Earliest symptoms of disease as a result of the activation of the body defenses fever, pain, soreness, swellingfever, pain, soreness, swelling Signs of inflammation: Signs of inflammation: edema - accumulation of fluid,edema - accumulation of fluid, granulomas and abscesses – walled-off collections of inflammatory cells and microbesgranulomas and abscesses – walled-off collections of inflammatory cells and microbes lymphadenitis – swollen lymph nodeslymphadenitis – swollen lymph nodes Major Factors in the Development of an Infection

27. 27 Microbe-Human Interactions Signs of Infection in the Blood Changes in the number of circulating white blood cells Changes in the number of circulating white blood cells leukocytosis – increase in white blood cellsleukocytosis – increase in white blood cells leukopenia – decrease in white blood cellsleukopenia – decrease in white blood cells septicemia – microorganisms are multiplying in the blood and present in large numberssepticemia – microorganisms are multiplying in the blood and present in large numbers bacteremia – small numbers of bacteria present in blood not necessarily multiplying bacteremia – small numbers of bacteria present in blood not necessarily multiplying viremia – small number of viruses present not necessarily multiplying viremia – small number of viruses present not necessarily multiplying Major Factors in the Development of an Infection

28. 28 Microbe-Human Interactions Portals of Exit Pathogens depart by a specific avenue; greatly influences the dissemination of infection Pathogens depart by a specific avenue; greatly influences the dissemination of infection respiratory – mucus, sputum, nasal drainage, salivarespiratory – mucus, sputum, nasal drainage, saliva skin scalesskin scales fecal exitfecal exit urogenital tracturogenital tract removal of bloodremoval of blood Major Factors in the Development of an Infection

29. 29 Microbe-Human Interactions Persistence of Microbes and Pathologic Conditions Apparent recovery of host does not always mean the microbe has been removed. Apparent recovery of host does not always mean the microbe has been removed. Latency – after the initial symptoms in certain chronic diseases, the microbe can periodically become active and produce a recurrent disease; person may or may not shed it during the latent stage Latency – after the initial symptoms in certain chronic diseases, the microbe can periodically become active and produce a recurrent disease; person may or may not shed it during the latent stage Chronic carrier – person with a latent infection who sheds the infectious agent Chronic carrier – person with a latent infection who sheds the infectious agent Sequelae – long-term or permanent damage to tissues or organs Sequelae – long-term or permanent damage to tissues or organs Major Factors in the Development of an Infection

30. 30 Microbe-Human Interactions Sources and Spread of Microbes Reservoirs: Where Pathogens Persist Reservoir – primary habitat of pathogen in the natural world Reservoir – primary habitat of pathogen in the natural world human or animal carrier, soil, water, plantshuman or animal carrier, soil, water, plants Source – individual or object from which an infection is actually acquired Source – individual or object from which an infection is actually acquired

31. 31 Microbe-Human Interactions Sources and Spread of Microbes Reservoirs: Where Pathogens Persist => Living Reservoirs Carrier – an individual who inconspicuously shelters a pathogen and spreads it to others; may or may not have experienced disease due to the microbe Carrier – an individual who inconspicuously shelters a pathogen and spreads it to others; may or may not have experienced disease due to the microbe Asymptomatic carrier – Asymptomatic carrier – incubation carriers – spread the infectious agent during the incubation periodincubation carriers – spread the infectious agent during the incubation period convalescent carriers – recuperating without symptomsconvalescent carriers – recuperating without symptoms chronic carrier – individual who shelters the infectious agent for a long periodchronic carrier – individual who shelters the infectious agent for a long period Passive carrier – contaminated healthcare provider picks up pathogens and transfers them to other patients Passive carrier – contaminated healthcare provider picks up pathogens and transfers them to other patients

32. 32 Microbe-Human Interactions Sources and Spread of Microbes Reservoirs: Where Pathogens Persist => Living Reservoirs -> Animals as Reservoirs and Sources A live animal (other than human) that transmits an infectious agent from one host to another is called a vector. A live animal (other than human) that transmits an infectious agent from one host to another is called a vector. Majority of vectors are arthropods – fleas, mosquitoes, flies, and ticks Majority of vectors are arthropods – fleas, mosquitoes, flies, and ticks Some larger animals can also spread infection – mammals, birds, lower vertebrates. Some larger animals can also spread infection – mammals, birds, lower vertebrates. Biological vectors – actively participate in a pathogen’s life cycle Biological vectors – actively participate in a pathogen’s life cycle Mechanical vector – not necessary to the life cycle of an infectious agent and merely transports it without being infected Mechanical vector – not necessary to the life cycle of an infectious agent and merely transports it without being infected

33. 33 Microbe-Human Interactions Sources and Spread of Microbes Reservoirs: Where Pathogens Persist => Living Reservoirs -> Animals as Reservoirs and Sources An infection indigenous to animals but naturally transmissible to humans is a zoonosis (animal disease). An infection indigenous to animals but naturally transmissible to humans is a zoonosis (animal disease). Humans don’t transmit the disease to others. Humans don’t transmit the disease to others. At least 150 zoonoses exist worldwide; make up 70% of all new emerging diseases worldwide. At least 150 zoonoses exist worldwide; make up 70% of all new emerging diseases worldwide. Impossible to eradicate the disease without eradicating the animal reservoir Impossible to eradicate the disease without eradicating the animal reservoir

34. 34 Microbe-Human Interactions Sources and Spread of Microbes => Living Reservoirs -> Animals as Reservoirs and Sources

35. 35 Microbe-Human Interactions Sources and Spread of Microbes Reservoirs: Where Pathogens Persist => Nonliving Reservoirs Soil (such as fungi, spores, anthrax bacillus, Clostridium botulinum,…), water, and air Soil (such as fungi, spores, anthrax bacillus, Clostridium botulinum,…), water, and air

36. 36 Microbe-Human Interactions Sources and Spread of Microbes Acquisition and Transmission of Infectious Agents Communicable disease – when an infected host can transmit the infectious agent to another host and establish infection in that host Communicable disease – when an infected host can transmit the infectious agent to another host and establish infection in that host Highly communicable disease is contagious. Highly communicable disease is contagious. Non-communicable infectious disease does not arise through transmission from host to host. Non-communicable infectious disease does not arise through transmission from host to host. occurs primarily when a compromised person is invaded by his or her own normal microfloraoccurs primarily when a compromised person is invaded by his or her own normal microflora contact with organism in natural, non-living reservoircontact with organism in natural, non-living reservoir

37. 37 Microbe-Human Interactions Sources and Spread of Microbes Acquisition and Transmission of Infectious Agents Patterns of Transmission Direct contact – physical contact or fine aerosol droplets Direct contact – physical contact or fine aerosol droplets Indirect contact – passes from infected host to intermediate conveyor and then to another host Indirect contact – passes from infected host to intermediate conveyor and then to another host vehicle – inanimate material, food, water, biological products, fomitesvehicle – inanimate material, food, water, biological products, fomites airborne – droplet nuclei, aerosolsairborne – droplet nuclei, aerosols

38. 38 Microbe-Human Interactions Sources and Spread of Microbes Nosocomial Infections – Hospital as a source of infection Diseases that are acquired or developed during a hospital stay Diseases that are acquired or developed during a hospital stay From surgical procedures, equipment, personnel, and exposure to drug-resistant microorganisms From surgical procedures, equipment, personnel, and exposure to drug-resistant microorganisms More than 1/3rd of nosocomial infections could be prevented. More than 1/3rd of nosocomial infections could be prevented. 2 to 4 million cases/year in U.S. with approximately 90,000 deaths 2 to 4 million cases/year in U.S. with approximately 90,000 deaths Most commonly involve urinary tract, respiratory tract, and surgical incisions Most commonly involve urinary tract, respiratory tract, and surgical incisions Most common organisms involved: Gram-negative intestinal flora Most common organisms involved: Gram-negative intestinal flora E. coli, Pseudomonas, StaphylococcusE. coli, Pseudomonas, Staphylococcus -> to prevent take universal precautions

39. 39 Microbe-Human Interactions Epidemiology The study of the frequency and distribution of disease and health-related factors in human populations The study of the frequency and distribution of disease and health-related factors in human populations Surveillance –collecting, analyzing, and reporting data on rates of occurrence, mortality, morbidity and transmission of infections Surveillance –collecting, analyzing, and reporting data on rates of occurrence, mortality, morbidity and transmission of infections Reportable, notifiable diseases must be reported to authorities. Reportable, notifiable diseases must be reported to authorities. Centers for Disease Control and Prevention (CDC) in Atlanta, GA – principal government agency responsible for keeping track of infectious diseases nationwide and worldwide Centers for Disease Control and Prevention (CDC) in Atlanta, GA – principal government agency responsible for keeping track of infectious diseases nationwide and worldwide http://www.cdc.gov http://www.cdc.gov http://www.cdc.gov

40. 40 Microbe-Human Interactions Koch’s Postulates Determining the causative or etiologic agent of infectious disease: Determining the causative or etiologic agent of infectious disease: Find evidence of a particular microbe in every case of a disease. Find evidence of a particular microbe in every case of a disease. Isolate that microbe from an infected subject and cultivate it artificially in the laboratory. Isolate that microbe from an infected subject and cultivate it artificially in the laboratory. Inoculate a susceptible healthy subject with the laboratory isolate and observe the resultant disease. Inoculate a susceptible healthy subject with the laboratory isolate and observe the resultant disease. Reisolate the agent from this subject. Reisolate the agent from this subject.