121 terms

MICRO 1.03c - Host and Microbial Relationships

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Infection
o Invasion or colonization of the body by pathogenic microorganisms (without signs and symptoms)
o Leads to alteration in the human microbiome
o Pathogenesis of bacterial infection includes initiation of the infectious process and the mechanisms that lead to development of signs and symptoms.
Transmissibility
Adherence to host cells
Invasion of host cells and tissues
Toxigenicity
Ability to invade the host's immune system
o Characteristics of pathogenic bacteria include:__________


o Many infections caused by pathogenic bacteria are unapparent or asymptomatic and can cause sufficient harm to the person.
Disease
o Occurs when an infection results in any change of the normal state of health
• Infectious disease
o Caused by pathogenic organisms (bacteria, parasites, fungi, viruses) that can be spread directly or indirectly between hosts
o Caused by unsuccessful relationship between host and parasite
ADherance

o Process by which bacteria stick to the surface of host cells
o A major step in initiation of the infection process once bacteria have entered the body
o May often be used interchangeably with adhesion and attachment
• Carrier
o A person or animal with asymptomatic (not showing symptoms) infection which carries the infectious agent and can transmit it to another susceptible host
Invasion

o Process whereby bacteria, parasites, fungi, and viruses enter the host's cells and tissues and spread into its body
Non-pathogen

o An organism that does not cause a disease
o Normally includes those that are part of our normal microflora
• Opportunistic pathogen
o Agent that is capable of causing a disease only when the host's resistance is impaired
o May or may not be a part of the normal microflora
Pathogen

o A microorganism capable of causing a disease
Toxicity

o The ability of a microorganism to produce a toxin that contributes to the development of the disease
Virulence

o Quantitative ability of an agent to cause a disease when introduced into the host in small numbers
o Degree of pathogenicity of a microorganism as indicated by case fatality rates and/or its ability to invade the tissues of the host
o Competence of any infectious agent to produce pathologic effects
KOCH'S POSTULATES


1. The same pathogen must be present in every case of the disease.
2. The pathogen must be isolated from the diseased host and grown into pure culture.
3. The pathogen from the pure culture must cause the disease when inoculated into a healthy susceptible laboratory animal.
4. The pathogen must be isolated from the inoculated animal and must be shown to be same as the originally inoculated.
• Four criteria that were established by Robert Koch to identify the causative agent of particular disease

1. The same pathogen must be _______________.
2. The pathogen must be_________
3. The pathogen from the pure culture must__________
4. The pathogen must be isolated from the inoculated animal and____________
syphilis, leprosy (need live animal)

Tetanus - trismus/lockjaw, generalized spasms
EXCEPTIONS TO KOCH'S POSTULATE
• Koch's postulates are modified to establish etiologies of diseases caused by viruses and some bacteria, which cannot be grown on artificial media
o Ex.___________
• Some diseases have distinguishing signs and symptoms that no other microbe can produce
o Tetanus - _________
o Diphtheria
o Rabies - hydro- and aerophobia
• Some diseases like pneumonia and nephritis may be caused by a variety of microbes (pneumonia, nephritis, pharyngitis)
• Some pathogens, such a S. pyogenes, cause several different diseases (erysipelas, cellulitis, necrotizing fascilitis)
• Certain pathogens cause disease in humans only
o HIV, measles
MOLECULAR KOCH'S POSTULATE
1. The phenotype or property under investigation should be significantly associated with pathogenic strains of a species and not with non-pathogenic strains.
2. Specific inactivation of the gene or associated genes with the suspected virulence trait should lead to a measurable decrease in pathogenicity or virulence.
3. Reversion or replacement of the mutated gene with the wild type gene should lead to restoration of pathogenicity or virulence
MOLECULAR KOCH'S POSTULATE
1. The phenotype or property under investigation should be significantly associated with ______
2. Specific inactivation of the gene or associated genes with the suspected virulence trait should lead to a measurable ____________
3. Reversion or replacement of the mutated gene with the wild type gene should lead to ____________
SUMMARY FOR "MOLECULAR GUIDELINES
FOR ESTABLISHING MICROBIAL DISEASE CAUSATION"
1. Nucleic acid of pathogen must be found WHERE the infection is. (Host orits part affected)
2. Nucleic acid of pathogen in diseased hosts > healthy individuals
3. When disease is present, so is the nucleic acid of pathogen
4. If the nucleic acid of the pathogen gives consistent clues to deduce the phenotype/characteristic of the pathogen involved, then the significance of detected microbial sequence is increased
SUMMARY FOR "MOLECULAR GUIDELINES
FOR ESTABLISHING MICROBIAL DISEASE CAUSATION"
1. Nucleic acid of pathogen must be found __________ (Host orits part affected)
2. Nucleic acid of pathogen in diseased hosts___ healthy individuals
3. When disease is present, so is the _______of pathogen
4. If the nucleic acid of the pathogen gives consistent clues to deduce the phenotype/characteristic of the pathogen involved, then the significance of detected microbial sequence is ______
Communicable Disease


Chickenpox, measles, tuberculosis
o Spreads from one host to another, either directly or indirectly
o ______________ (all these 3 spreads through respiratory tract)
Noncommunicable Diseases


Ex. ruptured appendix, tetanus from "rusty nail"
o Does not spread from one host to another
o Caused by microorganisms that normally inhabit the body and occasionally produce disease, or by microorganisms that reside outside the body and produce disease only when introduced into the body
o
Herd Immunity

Mass vaccination (measles, polio)

o Indirect protection from disease due to there being a high number of immune individuals in the population.
o The more immune individuals, the harder it is for the disease to be spread among many people; the cycle of transmission is broken.
o ______
o The goal of Expanded Program of Immunization
Notifiable Disease
Ex. TB, SARS, AH1N1

o Potentially harmful diseases which must be reported by the physicians
o Allows authorities to keep track and plan for intervention
o
Incidence
o Number of people in a population who develop a disease during a particular time period
o Indicator of the spread of the disease
Prevalence
o Number of people in a population who develop a disease at a specified time, regardless of when it appeared
o Takes into account both new and old cases
o Indicator of how seriously and how long a disease affects the population
1. Sporadic Disease
o
o Ex. Polio, meningococcemia
Disease occurs only occasionally
1. Endemic Disease
Ex. Tuberculosis in Filipinos, Malaria in Palawan
Disease constantly present in a population
1. Epidemic Disease
o
o Ex. Dengue, cholera
If many people in a given area acquire a certain disease in a relatively short period
1. Pandemic Disease
o o Ex. HIV, Influenza AH1N1
Epidemic spreads worldwide
• Acute Disease
o
o Ex. Viral diarrhea that last for around 5-7 days
Develops rapidly but lasts only a short time
• Chronic Disease
o
o Ex. TB, hepatitis
Develops more slowly (bet. > 2 weeks to >3 months) and the body's reaction may be less severe, but the disease is likely to be continual or recurrent for long periods.
• Subacute Disease
o
o Ex. Lyme disease
Intermediate between acute and chronic disease, you may have had the disease but you did not manifest full blown signs and symptoms
• Latent Disease
o
o Example: Chickenpox reactivation to become Zoster
Causative agent remains inactive for a time but then becomes active to produce signs and symptoms
o Latency = "quiet period"
1. Incubation Period
2. Prodromal Period
3. Illness/acute/invasive Period
4. Decline Period
5. Convalescent Period
STAGES OF DISEASE
INCUBATION PERIOD

• Ex. Dengue incubation period is 4 days
• The time interval between the initial infection and the first appearance of any signs or symptoms
• Period ends when the symptoms appear
• Depends on the specific microorganism, its virulence, the number of infecting microbes and host factors
PRODROMAL PERIOD

• Ex. measles: there is a prodrome before you develop the rash cough, colds, conjunctivitis, spots on the skin
• Relatively short period that follows the incubation period
• Marked by early, mild symptoms of disease, such as general aches and malaise (not present in all disease)

• Not every disease have prodromal stage
ILLNESS/ACUTE/INVASIVE PERIOD

In cholera, massive diarrhea contributes to contamination of water bodies
o In tuberculosis, coughing causes production of aerosol
• Disease is most acute/active; person exhibits overt signs and symptoms of disease
• Clinical manifestations of disease often promote transmission
o
• Generally, the patient's immune response and other defense mechanisms overcome the pathogen
• When disease is not successfully overcome, patient dies during this period
• Can serve as reservoir of disease and easily spread the disease to other people
DECLINE PERIOD
• Signs and symptoms subside
• May take from less than 24 hours to several days
• Patient is vulnerable to secondary infections
CONVALESCENT PERIOD
• Patient regains strength and the body returns to its pre-diseased state
• Recovery period
1. Direct contact transmission
o touching, kissing, and sexual contact
Person-to-person transmission
o Direct transmission of an agent by physical contact between its source and a susceptible host; no intermediate object is involved
o Most common forms:
2. Indirect contact transmission
o Agent of disease is transmitted from its reservoir to a susceptible host by means of a nonliving object (fomite)
3. Droplet transmission

coughing, sneezing, laughing or talking and travel less than 1 meter from the reservoir to the host
o Microbes are spread in droplet nuclei (mucus droplets) that travel only short distances
o Discharged into the air by
1. Waterborne

o Cholera, shigellosis, leptospirosis
o Pathogens spread via water contaminated with untreated or poorly treated sewage
2. Foodborne

Food poisoning, salmonella infections, tapeworm infections
o Pathogens generally transmitted in foods that are incompletely cooked, poorly refrigerated, or prepared under unsanitary conditions
o
3. Airborne
o
Ex. Spitting in public places very dangerous especially when not exposed to sunlight;
M. tuberculosis produces respiratory disease with cough and production of aerosols
Spread of agents of infection by droplet nuclei in dust that travel more than 1 meter from the reservoir to the host.
o Droplets are small enough to remain airborne for prolonged periods
1. Mechanical
o
o Houseflies walking on feces, spread germs to humans
Passive transport of the pathogens on the insect's feet or other body parts
2. Biological
o
o Pathogens then reproduce in the vector and transmit it to another host by several means: bite, defecation, vomiting
Active process; more complex
o Arthropod bites an infected person or animal and ingests some of the infected blood.
mucous membrane
skin
parenteral route
portals of entry
1. Respiratory tract
o Easiest and most frequently traveled portal of entry
o Inhaled into the nose or mouth in drops of moisture and dust particles
o Ex. common cold, pneunomia, influenza, TB
2. Gastrointestinal tract
o In food and water via contaminated fingers
o Those microbes which survive HCl in the stomach cause disease
o Often eliminated with feces and can be transmitted to other hosts via contaminated water, food, or fingers
o Cause poliomyelitis, hepatitis A, typhoid fever, shigellosis
3. Genitourinary tract
o For pathogens contracted sexually
o Some may penetrate an unbroken mucous membrane, others require a cut or abrasion of some type
o Ex. HIV infection, genital warts, herpes, syphilis, gonorrhea
SKIN
• One of the largest organs in terms of surface area
• Intact skin is impermeable by most microbes
• Some microbes gain access through skin openings like hair follicles and sweat gland ducts
• Significant during rainy season - leptospirosis
PARENTERAL ROUTE
• Microbes get deposited directly into the tissues beneath the skin or into mucous membranes when these barriers are injured
• Punctures, injections, bites, cuts, wounds, surgery
CRITICAL STEPS ON HOW MICROORGANISMS ACT
AS AGENTS OF DISEASE
1. Encountering the host
2. Locating the niche/Finding a favorable environment
3. Evade normal host defense mechanism
4. Procreate on or in the host
5. Maintain its existence in association with the host and cause an unfavorable host response disease
CRITICAL STEPS ON HOW MICROORGANISMS ACT
AS AGENTS OF DISEASE
1. Survival in an arthropod host (Ex. Malaria and Dengue)
2. Survival in an aerosol droplet (Ex. M. tuberculosis)
3. Survival in a hostile environment (Ex. C. tetani, B. anthracis)
4. Production of structures that can contribute to dissemination (fungal spore formation)
ENCOUNTERING THE HOST
• Factors that contributes to the ability of the organism to encounter a favourable host
1. Survival in an arthropod host (Ex. __)
2. Survival in an aerosol droplet (Ex. __)
3. Survival in a hostile environment (Ex. ___)
4. Production of structures that can contribute to dissemination (____)
motility
adherence factors
enzymes
previous infection/damage
ability to survive adverse host environment
ability to directly invade host epithelium to reach favorable environment
LOCATING THE NICHE/
FINDING A FAVORABLE ENVIRONMENT
MOTILITY
• Flagella or other mechanisms
• Allow microbes to penetrate mucous layers of the epithelial cells (ex. Helicobacter pylori)
• Chemotactic attractants and other features on the host encourage microbial contact with the appropriate surface
• Flagella or other mechanisms
• Allow microbes to penetrate mucous layers of the epithelial cells (ex. _____)
• _________ and other features on the host encourage microbial contact with the appropriate surface
ADHERENCE FACTORS

Surface hydrophobicity and net surface charge
o Bacteria and host cells commonly have net negative surface charges and, therefore, repulsive electric forces
o The more hydrophobic the bacterial cell surface, the greater the adherence to host cell.
• Factors affecting interaction between bacteria and tissue surface in adhesion process
• Surface ___and net surface charge
o Bacteria and host cells commonly have net ______surface charges and, therefore, _______electric forces
o The more ______the bacterial cell surface, the greater the _______to host cell.
Adhesins/ Ligands
o surface molecules on the pathogen which attach to the receptors on the cells of certain host tissues
o May be located on a microbe's glycocalyx or on other microbial surface structure, such as fimbriae
o Majority are glycoproteins or lipoproteins
Pili
- help mediate adherence to host cell surfaces
Fimbriae
o Extend from bacterial cell wall/glycocalyx,
Lipoteichoic acid and Protein F:
cause adherence of streptococci to buccal epithelial cells; adherence mediated by fibronectin(host cell receptor molecule)
M protein:
acts as antiphagocytic agent and is a major virulence factor
ENZYMES
• Adds to virulence of some microbes
• Break cells open, dissolve materials between cells, and form or dissolve blood clots
• Modify the local environment to provide a more hospitable home
1. Leukocidins
o
o Ex. staphylococci; streptococci
Destroy neutrophils, leukocytes, & macrophages which are active in phagocytosis
2. Hemolysins
o
Cause the lysis of erythrocytes
o Different species differ in ability to lyse RBC
o Different types of lysis: α-hemolytic, β-hemolytic, etc.
3. Coagulases
o
Coagulate/clot fibrinogen in blood
o Fibrinogen , a plasma protein produced by the liver, is converted by coagulases into fibrin, the threads that form a blood clot
protect bacterium from phagocytosis and isolate it from other host defenses
4. Kinases
o
o Ex. streptokinase; staphylokinase
Break down fibrin and thus dissolve clots formed by the body to isolate the infection
5. Hyaluronidase
o
Hydrolyzes hyaluronic acid, a polysaccharide that holds together the connective tissue
o Digesting action involved in the tissue blackening of infected wounds and help microorganisms spread to distant sites
6. Collagenase
o
o Ex. Clostridium perfringens (causing gangrene)
Breaks down the protein collagen, which forms the connective tissue of muscles and other body organs and tissues.
7. 1gA1 protease
o Neisseria gonorrhoeae,
N. meningitidis, Haemophilus influenza, and Streptococcus pneumoniae
Split IgA1 at specific proline-threonine or proline-serine bonds in the hinge region and inactivate its antibody activity
o Important virulence factor of _______
o Production allows pathogens to inactivate the primary antibody found in mucosal surfaces, thereby eliminating protection of the host by the antibody
PREVIOUS INFECTIONS AND TISSUE DAMAGE
• Can predispose host to more severe disease
• Ex. effect of influenza virus to the lung tissue: denuding the cilia in the lining of the respiratory tract superinfection with bacteria causing pneumonia
Gastric acidity - Salmonella survival
ABILITY TO SURVIVE ADVERSE HOST ENVIRONMENTS
• Ex.
ABILITY TO DIRECTLY INVADE HOST EPITHELIUM TO REACH FAVOURABLE ENVIRONMENT
• Bacteria produce virulence factors that influence host cells, causing them to engulf/ingest the bacteria
• Host cells play an active role in the process
• Direct entry of Entamoeba histolytica to the intestinal cells
• Yersinia enterocolitica adheres to host cell membrane and cause it to extrude protoplasmic projections, causing host cell to engulf bacteria

Listeria monocytogenesadheres to and readily invades macrophages and cultured and undifferentiated intestinal cells
ABILITY TO DIRECTLY INVADE HOST EPITHELIUM TO REACH FAVOURABLE ENVIRONMENT
• Bacteria produce virulence factors that influence host cells, causing them to engulf/ingest the bacteria
• Host cells play an active role in the process
• Direct entry of _________to the intestinal cells
• __________adheres to host cell membrane and cause it to extrude protoplasmic projections, causing host cell to engulf bacteria
__________adheres to and readily invades macrophages and cultured and undifferentiated intestinal cells
1. Production of extracellular matrices
2 Ability to induce "nonprofessional" phagocytic cells to engulf the microbe
3. Ability to survive intracellularly inmacrophages
4. Production of extracellular substances that inactivate cellular immune response
5. Substances produced can interfere with humoral immune response
EVADING HOST DEFENSES
1. Production of extracellular matrices
o Polysaccharide capsule formation - impairs phagocytosis by preventing phagocytic cell from adhering to the bacterium
o Ex. Streptococcus pneumoniae
2 Ability to induce "nonprofessional" phagocytic cells to engulf the microbe
o Ex. Chlamydia trachomatis can only be endocytosed by human squamo-columnar cells of the human genital tract
3. Ability to survive intracellularly inmacrophages
o Ex. Mycobacterium tuberculosis and Legionella sp. can survive within polymorphonuclear cells by:
Avoiding entry into phagolysosomes and living within cytosol
Preventing phagosome-lysosome fusion and living within the phagosome
Being resistant to lysosomal enzymes and surviving within the phagolysosome
4. Production of extracellular substances that inactivate cellular immune response
o Ex. Hemolysins directly destroy leukocytes; HIV virus destroys T helper cells
5. Substances produced can interfere with humoral immune response
o Ex. IgA proteases destroy IgA immunoglobulin surface proteins of S. aureus prevent antibody function
EXOTOXIN
1. Excreted by living cell; high concentrations in liquid medium
2. Produced by both G(+) and (-) bacteria
3. Polypeptides with molecular weight of 10k-900k kDa
4. Relatively unstable
5. Highly antigenic
6. Converted to antigenic toxoids
7. Highly toxic (concentrations as low as micrograms can produce toxic effect)
8. Bind to specific receptors
9. Does not cause fever
10. Frequently controlled by plasmids
ENDOTOXIN
1. Integral part of the cell wall of G(-) bacteria; may not need to be released to have biologic activity
2. Found only in G(-) bacteria
3. Lipopolysaccharide complexes/Lipid A portion responsible for toxicity
4. Relatively stable (can withstand 60oC for hours
5. Weakly immunogenic; antibodies are antitoxic and protective
6. Not converted to toxoids
7. Moderately toxic
8. No receptors on cells
9. Causes fever
10. Synthesis directed by chromosomal genes
toxoids
o - vaccines made from modified exotoxins to negate toxicity.
Cytotoxins

- Kill host cells or affect their functions
-
Corynebacterium diphtheriae - erythrogenic

- Clostridium perfringens - produce lecithinase that damages cell membranes and theta toxin that has a necrotizing effect


- Staphylococcus aureus - elaborate toxic shock syndrome (toxin-1, a super antigen, stimulates T-lymphocytes to produce large amounts of TNF and IL-1)
Neurotoxins

- Interfere with normal nerve impulse transmission

- Cl. botulinum - botulinum toxin

- Cl. tetani - tetanospasmin toxin (cause tetanus)
Enterotoxins

- Affect cells by lining the GIT

- Vibrio cholera - epidemic diarrheal disease


- S. aureus - staphylococcal enterotoxin stimulates vomiting center in the CNS (often cause projectile vomiting) and is the most common cause of food poisoning

o Cough and gag reflex - prevent particles from entering lungs
o Sneezing - expels infectious agents
o Swallowing - to move pathogens to the stomach
MECHANICAL BARRIERS

Reflexes
• Intact skin
o Inhibitory action of sebaceous glands
o Dry surface not conducive to microbial growth
o Continuous sloughing of epithelial cells carry adherent microbes away
o Flushing action of sweat removes microbes;
o Lysozymes also have inhibitory substances
MECHANICAL BARRIERS

intact skin
• Conjunctiva
o Flushing action of blinking and tears prevents colonization
o Lysozyme and other antibacterial substances hydrolyze a structural polysaccharide in bacterial cell walls
MECHANICAL BARRIERS

conjuctiva

o Mucus layers (ex. phlegm) entrap microorganisms and swept by ciliary action into the throat to be swallowed
o Presence of lysozyme in secretions
o Cilia prevent aerosol-borne agents from entering the lungs (movement of cilia is away from the lungs)
MECHANICAL BARRIERS

Mucous membrane epithelium
• Gastrointestinal tract
o Saliva flushes away microbes
o Presence of lysozyme destroys bacteria
o Stomach acidity and proteolytic enzymes destroy bacteria
o Bile is inhibitory to the growth of many bacteria
o Normal peristalsis forces organisms to move along the GI tract and excreted in the feces
o Mucosal layer protects epithelial cells
MECHANICAL BARRIERS

• Gastrointestinal tract
• Urinary tract
o Flushing of urine prevents bacterial population build up
o Acidity of urine is inhibitory to some organisms
MECHANICAL BARRIERS

urinary tract
• Genital tract
o Vaginal epithelium is sloughed rapidly and carries with it transient microbes
o Acidic vaginal secretions contain antimicrobial substances; also promote flushing of microorganisms from the body
MECHANICAL BARRIERS

genital tract
complement
interferon alpha & gamma
fibronectin
SOLBULE AND CIRCULATING NONSPECIFIC EFFECTORS
Complement

o Comprised of at least 20 proteins and glycoproteins
o Lyse microbial membranes and release inflammation enhancing substances
• Interferon - α (IF-α)
o Released by cells infected with virus
o Protect neighboring cells from viral multiplication by inducing production of intracellular antiviral proteins
• Interferon γ (IF-γ)
o Activates macrophages to phagocytose and destroy intracellular parasites more effectively
o Interrupts viral replication and promotes T-cell differentiation
• Fibronectin
o Produced by some macrophages and epithelial cells
o Nonspecific opsonin for certain microbes
• Alveolar macrophages

• Polymorphonuclear neutrophils

• Eosinophils

• Fixed macrophages


• Lactoferrin
CELLULAR NONSPECIFIC IMMUNE RECEPTORS
• Alveolar macrophages
o Remove particles and organisms that enter the alveoli
• Polymorphonuclear neutrophils
o First phagocytes into an infected area
secretory IgA
Serum IgG
IgM
HUMORAL IMMUNE SYSTEM
• Fixed macrophages
o Histiocytes
o Found in the tonsils and Kupffer cells of the liver
o Remove microorganisms
eosinophils
o Important in the removal of immune complexes
Lactoferrin

o Released by activated macrophages and PMNs,
o Causes sequestration of iron from plasma
o Reduces the amount of iron available to invading organisms and limits their ability to multiply
• Secretory IgA
o Found in mucus secretions
o Can bind to infectious agents and prevent attachment
• Serum IgG
o Neutralize viruses and prevent them from entering cells
o Act as opsonin for bacteria
o Initiates the complement cascade when bound to antigen
• IgM
o Initiate the complement cascade and aid in phagocytosis of bound bacteria (IgM as in Mauuna)
• Primary exposure = IgM, second exposure = IgG (via memory cells)
• Primary exposure = , second exposure = (via memory cells)
T lymphocytes (T helper cells)
Cytotoxic T cells
B cells
CELLULAR IMMUNE SYSTEM
• T LYMPHOCYTES (T HELPER CELLS)
o Enhance antibody production by B lymphocytes
• CYTOTOXIC T CELLS
o Kill virus-infected host cells directly
• B CELLS
o Stimulated by the binding of T- independent antigens, such as flagellar structures, to produce antibodies primarily IgM
Staphylococcus epidermidis and S. aureus - central venous catheter infection, eye infection (contact lens), dental plaque
o Pseudomonas aeruginosa- airway infection
THE ROLE OF BACTERIAL BIOFILM
• Biofilm is an aggregate of interactive bacteria attached to a solid surface or to each other encased in an exopolysaccharide matrix.
• Form slim coat on a hard surface throughout surface
• Important in human infections that are persistent and difficult to treat
• Usually more resistant to antimicrobial than when alone
• Individuals found deeper the biofilm has lower metabolism
• Examples:
o
Colonization
o Motility: Flagella
o Adherence: Pili
• Release of quorum sensing signals
BIOFILM FORMATION
• Colonization
o Motility: ___
o Adherence: ++++
• _________accumulate, resulting in a modification of the metabolic activity of the bacteria.
o Ex. acylhomoserine lactone signal - "nagtatawag ng resbak", similar to chemotaxis
• If certain number is released, they start to produce exopolysaccharide
• The exopolysaccharide matrix may be protected from the host's immune mechanisms.
• The matrix also functions as a diffusion barrier for some antimicrobials but, other antimicrobials may bind to it.
•open bench tops using standard microbiological practices

Examples: Bacillus subtilis, Saccharomyces cerevisiae
BIOSAFETY LEVEL 1 (BSL-1)
• Suitable for work involving well-characterized agents not known to consistently cause disease in immunocompetent adult humans and present minimal potential hazard to laboratory personnel and the environment
• Not necessarily separated from the general traffic patterns in the building
• Work is typically conducted on _________
• Special containment equipment or facility design is not required, but may be used as determined by appropriate risk assessment
• Laboratory personnel must have specific training in the procedures conducted in the laboratory and must be supervised by a scientist with training in microbiology or a related science
Example agents: pathogenic E. coli, Salmonella, P. falciparum, S. auerus, Hepatitis A-C viruses
BIOSAFETY LEVEL 2 (BSL-2)
• Suitable for work involving agents that pose moderate hazards to personnel and the environment
• Differences from BSL-1:
o Laboratory personnel have specific training in handling pathogenic agents and are supervised by scientists competent in handling infectious agents and associated procedures
o Access to the laboratory is restricted when work is being conducted
o All procedures in which infectious aerosols or splashes may be created are conducted in biosafety cabinets or other physical containment equipment
Example agents: Bacillus anthracis, Mycobacterium tuberculosis, HIV, SARS coronavirus
BIOSAFETY LEVEL 3 (BSL-3)
• High biohazard, multiple vaccinations required
• Applicable to clinical, diagnostic, teaching, research, or production facilities where work is performed with indigenous or exotic agents that may cause serious or potentially lethal disease through the inhalation route of exposure
• Laboratory personnel must receive specific training in handling pathogenic and potentially lethal agents, and must be supervised by scientists competent in handling infectious agents and associated procedures
• All procedures involving the manipulation of infectious materials must be conducted within biosafety cabinets or other physical containment devices
• BSL-3 laboratory has special engineering and design features
Cabinet Laboratory - manipulation of agents must be performed in a Class III biosafety cabinet
o Suit Laboratory - personnel must wear a positive pressure supplied air protective suit (this is what the characters in Outbreak wear when they are inside the lab; the one with wires)


Example agents: Ebola, Lassa, & Hanta viruses
BIOSAFETY LEVEL 4 (BSL-4)
• Extreme biohazard, maximum security
• Highly virulent, no known cures or vaccines
• Required for work with dangerous and exotic agents that pose a high individual risk of aerosol-transmitted laboratory infections and life-threatening disease that is frequently fatal, for which there are no vaccines or treatments, or a related agent with unknown risk of transmission
• Agents with a close or identical antigenic relationship to agents requiring BSL-4 containment must be handled at this level until sufficient data are obtained either to confirm continued work at this level, or re-designate the level
• Laboratory staff must have specific and thorough training in handling extremely hazardous infectious agents
• Laboratory staff must understand the primary and secondary containment functions of standard and special practices, containment equipment, and laboratory design characteristics
• All laboratory staff and supervisors must be competent in handling agents and procedures requiring BSL-4 containment
• The laboratory supervisor in accordance with institutional policies controls access to the laboratory
• Two models for BSL-4 laboratories:
o _________
• BSL-4 cabinet and suit laboratories have special engineering and design features to prevent microorganisms from being disseminated into the environment
RELATIONS WITH THE FILM "OUTBREAK":

• Agent: Motaba virus
• Disease: communicable, acute at first
• 1st portal of entry: oral
• Modes of transmission
o Direct: kissing
o Indirect: airborne via air vent, needle prick, water
o Droplet: coughing
• Control & isolation: cohorting in one tent, use of personal protective equipment (PPEs)
• Treatment: antibodies from Betsy (the monkey, original host)
RELATIONS WITH THE FILM "OUTBREAK":

• Agent:
• Disease:
• 1st portal of entry:
• Modes of transmission
o Direct:
o Indirect:
o Droplet:
• Control & isolation:
• Treatment:
plot
A virus called Motaba causing a deadly fever is discovered in the African jungle in 1967. To keep the virus a secret, U.S. Army officers Donald McClintock and William Ford destroy the army camp where soldiers were infected.

In 1995, the virus resurfaces in Zaire. Colonel Sam Daniels, a USAMRIID virologist, is sent to investigate. He and his crew—Lieutenant Colonel Casey Schuler and new recruit Major Salt—gather information and return to the United States. Daniels asks his superior, (now) Brigadier General William Ford, to issue an alert but Ford tells Daniels the virus is unlikely to spread.

Betsy, a white-headed capuchin monkey (a host species for the virus), is smuggled into the United States. When James "Jimbo" Scott—an employee of the Biotest animal-holding facility—steals Betsy and brings her to Cedar Creek, California, to sell on the black market, he is infected. Jimbo fails to sell Betsy to Rudy Alvarez, a pet-store owner who wanted a male for a customer. Rudy is also infected, and "Jimbo" releases the female monkey in the woods. He develops symptoms on a flight to Boston and infects his girlfriend, Alice. They are hospitalized, and Dr. Roberta Keough—a CDC scientist and Daniels' ex-wife—investigates their illness. Jimbo, Alice, and Rudy die, but Keough determines that no one else in Boston was infected.

Technicians at a Cedar Creek hospital, including Henry, run tests on Rudy's blood; Henry is infected when he accidentally breaks a vial of Rudy's blood. It is later found that the virus mutated into a strain capable of spreading like influenza, and a number of people are exposed in a movie theater. Daniels learns about the infection and flies to Cedar Creek against Ford's orders, joining Keough's team with Schuler and Salt. As they begin a search for the host animal, the U.S. Army quarantines the town and imposes martial law. Schuler is infected when his suit tears, and Keough accidentally sticks herself with a contaminated needle. Ford provides an experimental serum to treat the sick (which fails because of the mutation), and Daniels realizes that he was aware of the virus before the outbreak. He confronts Ford, who admits that he withheld information to cover the fact that the original Motaba strain was purposefully engineered by the military as a bioweapon; the 1967 outbreak in Africa had in fact been a test-run of the virus, which subsequently infected the local monkey population despite Ford's and McClintock's attempt to halt its spread and cover their actions.
Daniels learns about Operation Clean Sweep, a plan for the military to bomb Cedar Creek which has been approved by the President; now-Major General Donald McClintock plans to use the operation to conceal the virus's existence. To prevent Daniels from finding a cure, McClintock has him arrested for carrying the virus. Daniels escapes, and he and Salt fly a helicopter to the ship which carried Betsy. Daniels obtains a picture of Betsy and releases it to the media; Mrs. Jeffries realizes that her daughter Kate has been playing with Betsy in their yard and calls the CDC. Daniels and Salt arrive at the Jeffries' house, and Salt tranquilizes Betsy after Kate coaxes her out of hiding. When he learns from Daniels about Betsy's capture, Ford delays the bombing.

On their return flight, Daniels and Salt are chased by McClintock in another helicopter, and Salt fires two rockets into the trees to trick McClintock into thinking that they crashed. In Cedar Creek, Salt mixes Betsy's antibodies with Ford's serum to create an antiserum; although Schuler has died, they save Keough. McClintock returns to base and resumes Operation Clean Sweep, refusing to listen to Ford (who wants to cancel it).

Daniels and Salt fly a helicopter in the path of the bomber, which is commanded by a pilot codenamed Sandman One. With Ford's help, Daniels persuades Sandman One and his co-pilot to detonate the bomb over water and spare the town. Before McClintock can order another bombing, Ford relieves him of his command and arrests him for withholding information from the president. Daniels and Keough reconcile, and Cedar Creek's residents are cured.
E
1. A 22-year-old woman who works in a plant nursery presents with a history of fever and cough for 2 months. Over this period of time she has lost 5 kg. Chest radiography shows bilateral upper lobe infiltrates with cavities. A stain of her sputum shows acid-fast bacilli. The likely means by which the patient acquired her infection is.

A. Sexual activity
B. Ingesting the microorganisms in her food
C. Holding onto contaminated hand rails when she takes public transportation
D. Handling potting soil
E. Breathing aerosolized droplets containing the microorganism
E
2. A 65-year-old woman has a long-term central venous catheter for intravenous therapy. She develops fever and subsequently has multiple blood cultures positive for Staphylococcus epidermidis. All of the S. epidermidis isolates have the same colony morphology and antimicrobial susceptibility pattern, suggesting that they are the same strain. A S. epidermidis biofilm is thought to be present on the catheter. Which one of the following statements about such an infection is correct?

A. The biofilm containing the S. epidermidis is likely to wash off the catheter.
B. Production of an extracellular polysaccharide inhibits growth of the S. epidermidis, limiting the infection.
C. The S. epidermidis in the biofilm are likely to be more susceptible to antimicrobial therapy because the bacteria have decreased rates of metabolism.
D. The quorum-sensing ability of S. epidermidis results in increased susceptibility to antimicrobial therapy.
E. The complex molecular interactions within the biofilm make it difficult to provide effective antimicrobial therapy, and it is likely the catheter will have to be removed to cure the infection.
A
3. Which of the following is most likely to be associated with the formation of a bacterial biofilm?

A. Airway colonization in a cystic fibrosis patient with a mucoid (alginate-producing) strain of Pseudomonas aeruginosa
B. Urinary tract infection with Escherichia coli
C. Meningitis with Neisseria meningitidis
D. Tetanus
E. Impetigo caused by Staphylococcus aureus