PATHOGENIC MICROBIOLOGY
Summary of Host-Parasite Interactions
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I. NATURAL
HABITATS FOR MICROBES
- Soil; Water; Air
- Animals and Animal Products
II. MICROBIAL
FLORA OF HUMAN BODY
- Skin: Gram-positive bacteria are
most common
- Respiratory Tract (actually external
to body)
- Mouth and oropharynx
- Saliva
- Teeth and gums (gingiva)
- Nose and nasopharynx
- Microorganisms can be aspirated
into the lower respiratory tract
- Larynx, trachea and bronchial
tubes (bronchi)
- Lungs: Superior and inferior
lobes (also middle lobe in right lung); Alveoli
- Eye (Conjunctivae)
- Ear: Inner, middle and exterior;
Exterior commonly colonized
- Gastrointestinal Tract (actually
external to body): Intestinal flora play a significant role in: Digestion;
Vitamin production (e.g., vitamin K); Ecological competition (see below) with
potentially pathogenic microorganisms
- Esophagus: Not typically colonized
- Gastric mucosa of stomach:
Acid tolerant organisms - Small intestine: Extends from
pylorus to ileo-cecal junction (about 20 feet in length);
Colonized by mostly anaerobes
- Villi (plural of
villus) and microvilli are finger-like projections that protrude
through the mucous membrane throughout the length of the small intestine
and are responsible for absorption
- Peyer’s patch: Aggregations
of lymphoid tissue concentrated in the ileum
- M (microfold) cells:
specialized cells in the Peyer’s patches that sample the microenvironment
and uptake foreign antigens for processing by underlying macrophages
- Duodenum: Upper
portion of small intestine (about 10 inches in length) encompassing
the superior, descending, transverse and ascending portions, in that
order; Hepatic ducts (from liver), pancreatic duct, and cystic duct
(from gallbladder) join and enter into the intestine at the descending
duodenum
- Jejunum (middle portion):
Upper two-fifths of remaining length of small intestine
- Ileum (lower portion):
Remaining three-fifths of length of small intestine
- Large intestine: Extends from
ileo-cecal valve to anus (about 5 feet in length); >1011
bacteria per gram of feces with anaerobes 1000-fold more common than other
microbes
- Cecum (a.k.a., Caecum):
Large, blind pouch just posterior to the ileo-cecal junction
- Colon: Ascending,
transverse, descending, and sigmoid portions
- Rectum
- Anus
- Special conditions of intestinal
tract
- Intestinal tract of newborn
- Antibiotic alteration of
flora
- Genitourinary Tract
- External genitalia
- Anterior urethra: Normally colonized
by avirulent organisms; May be transiently colonized by fecal organisms
that can cause disease; Neisseria gonorrhoeae and Chlamydia trachomatis
may cause disease or asymptomatically colonize - Urinary bladder: Not normally
colonized; May be transiently colonized with urethral organisms - Vagina: Microbial population
influenced by hormones - Cervix: Not normally colonized;
Neisseria gonorrhoeae and Chlamydia trachomatis are important pathogens
III. NORMALLY
STERILE SITES IN THE HUMAN BODY: Colonization of one of these sites generally
involves a defect or breach in the natural defenses that creates a portal of
entry
- Brain; Central nervous system
- Blood; Tissues; Organ systems
- Sinuses; Inner and Middle Ear
- Lower Respiratory Tract: Larynx;
Trachea; Bronchioles (bronchi); Lungs; Alveoli
- Kidneys; Ureters; Urinary Bladder;
Posterior Urethra
- Uterus; Endometrium (Inner mucous
membrane of uterus ); Fallopian Tubes; Cervix and Endocervix
IV. ECOLOGY DEFINITIONS
- Ecological Niche: Unique
environmental position occupied by a particular species, perceived in terms
of actual physical space occupied and function performed within the community
or ecosystem
- Flora (Microbiology Definition)
= Microbiota: Microorganisms present in or characteristic of a special
location (Flora more generically refers to plants; Fauna generically
refers to animals)
- Normal flora = Indigenous
or resident microbiota: Microbial flora typically occupying a particular
niche; Organisms tend to segregate given diversity of environmental conditions;
Many normal flora perform important functions for the host, including: digestive
and nutritional functions and competition with pathogenic microorganisms - Transient flora: Microbial
flora only temporarily associated with a particular niche - Endogenous flora: Microbial
flora occupying niches that are in or on the body of the host - Exogenous flora: Microbial
flora normally existing externally to the body of the host
V. ECOLOGICAL
RELATIONSHIPS
- Independence: Living free
from the influence, guidance, or control by another organism
- Benign Relationship (Commensalism):
Carrier
- Malignant Relationship
(Parasitism): Disease
- Benign: Referring to
a non-life or non-health threating condition; commensalism between host
and parasite - Carrier: Symptomless
individual who is host to a pathogenic microorganim and has the potential
to pass the pathogen to others - Malignant: Disease tending
to become progressively worse (Morbidity = illness) and potentially
result in death (Mortality = death)
- Microbial Interactions:
Complex relationships among species; Neutral, Antagonistic,
or Synergistic
- Host-Parasite Interactions:
Commensalism (+/0); Mutualism (+/+); Parasitism (+/-)
- Symbiosis: A relationship
in which two dissimilar organisms (Symbiotes, Symbionts) live in
close association with one another - Commensalism: A relationship
between two species in which one is benefited and the other is not affected,
neither negatively nor positively - Mutualism: Mutually beneficial
relationship between two species - Parasitism: A relationship
between two species in which one benefits (Parasite) from the other
(Host); Usually involves some detriment to the host
- True pathogen (a.k.a.,
Strict pathogen): Any microorganism capable of causing disease;
An infecting agent
- Opportunistic pathogen:
A usually harmless microorganism that becomes pathogenic under favorable
conditions; Often a member of the normal microbial flora
VI.
EPIDEMIOLOGY: Study of factors influencing occurrence, transmission, distribution,
prevention and control of disease
- Epidemic: Occurring suddenly
in numbers clearly in access of normal expectancy - Endemic: Present or usually
prevalent in a population or geographic area at all times - Pandemic: Widespread
epidemic distributed or occurring widely throughout a region, country, continent,
or globally
- Acquiring
Infectious Agents
- Portals (Routes) of
entry: Ingestion, inhalation, direct penetration - Carrier state: Symptomless
individual (host) that is colonized by a pathogenic microorganism and who
has the potential to pass the pathogen to others; Carriage may be transient
or (semi-) permanent - Nosocomial infections:
Infection acquired in a hospital setting that was not present in the host
prior to admission, generally occurring within 72 hours of admission - Opportunistic infections:
Infection caused by a normally harmless microorganism when certain predisposing
conditions (disease or conditions that increase host susceptibility) exist
- Transmission
of Disease
- Portals of entry/exit
- Vector: Living carrier,
especially the animal that transfers an infectious agent from one host to
another; Commonly an Arthropod - Fomite: Inanimate object
capable of transmitting microbes from one host to another, e.g., soiled
bed linens, diapers, tissues and handkerchiefs, hospital respiratory equipment,
etc.
VII. FACTORS CONTROLLING GROWTH
OF ORGANISMS
- Nutrient Availabilty:
The accessibility of a necessary resource, substance or compound providing
nourishment to maintain life, i.e. capable of conversion to energy and structural
building blocks
- Fastidious: an organism
that has complex nutritional or cultural requirements, making isolation
and culture more difficult
- Physico/Environmental Parameters
- Water activity/Osmotic pressure:
- Water activity (aw):
Represents the available water
- Osmotic pressure (p): Expressed
in atmospheres; Reflects the concentration of solute in an aqueous solution
- Oxygen: Pathogenic microorganisms
may have metabolic oxygen requirements that are Obligate or Facultative,
Anaerobic or Aerobic, or somewhere in between, Microaerophilic - pH: Power of hydrogen; Measurement
of the amount of hydrogen ion in solution; Logarithm of the reciprocal of
the hydrogen ion concentration in an aqueous solution used to express its
acidity or alkalinity (0-14) - Temperature:
- Psycrophile (psychrophilic):
Liking cold temperatures; Optimal growth at 15o to 20oC
- Mesophile (mesophilic):
Liking moderate temperatures; Optimal growth at 20o to 45oC
- Thermophile (thermophilic):
Liking elevated temperatures; Optimal growth at 50o to 70oC
- Competition: Simultaneous
demand by two or more organisms or species for a necessary, common resource
or physical space (niche) that is in limited or potentially limited supply,
resulting in a struggle for survival
- Host Immune System: The
cells and tissues involved in recognizing and attacking foreign substances
in the body
VIII. PATHOGENICITY vs. VIRULENCE
- Pathogenicity: Quality
of producing or the ability to produce pathologic changes or disease
- Virulence: Measurement
of the degree of disease producing ability of a microorganism as indicated
by the severity of the disease produced; Measure of the dosage (inoculum size)
required to caused a specific degree of pathogenicity; One general standard
is the LD50
- Virulence factors: Microbial
characteristics that enhance the ability to cause disease - Dosage (Inoculum size):
Number of pathogenic microorganisms entering the host - LD50 = Lethal Dose
50: Number of microorganisms required to cause lethality in 50% of the
test host
IX. INFECTION vs. DISEASE
- Infection: Colonization
and/or invasion and multiplication of pathogenic microrganisms in the host
with or without the manifestation of disease
- Colonization: Successful
occupation of a new habitat by a species not normally found in this niche - Multiplication: Ability
of a microorganism to reproduce and increase in numbers during an infection
- Disease: Abnormal condition
of body function(s) or structure that is considered to be harmful to the affected
individual (host); Any deviation from or interruption of the normal structure
or function of any part, organ, or system of the body; Dependent upon the
dosage and virulence of the organism/agent and varies inversely with the resistance
of the host
X. MICROBIAL PATHOGENICITY
- Factors that Influence the Degree
of Pathogenicity and the Progression of Infection and Disease
- Host factors: Age, sex, ethnicity,
nutrition (diet), hormonal status; personal hygiene and immune status; Underlying
disease or medical condition; Antibiotic or drug usage; Presence of foreign
object (e.g., splinter, catheter, sutures, etc.); Innate differences between
hosts - Microbial factors: Bacterial
virulence factors; Inoculum size (dosage) - External factors (e.g., crowding;
seasonal variations; hygiene, sanitation and public health; food processing,
storage and preparation; etc.)
- Progression of Infection and Disease
- Entrance (Portal of entry)
- Colonization (Adherence;
Adhesion; Attachment) - Multiplication with or without
dissemination (spread) - Penetration (Invasion)
(Note: Not all pathogens are invasive) - Signs and symptoms of disease
(Morbidity; Mortality) - Resolution or chronic state
may be established - Elimination and/or exit of pathogen
(Carrier state may be established)
- Damage to Host
- Direct damage
- Tissue damage
- Cell components and
metabolic by-products - Toxins
- Enzymes
- Organ necrosis:
Sum of morphological changes indicative of cell death and caused
by the progressive degradative action of cellular components, metabolic
by-products, enzymes and/or toxins
- Metabolic Effects: Pathogenic
organisms can affect any of the body systems with disruptions in metabolic
processes
- Indirect Damage: Damage to host
from excessive or chronic immune response (immunopathogenesis)
XI. VIRULENCE FACTORS
- Colonization Factors
- Attachment/Adherence:
Close association of bacterial cells and host cells generally characterized
by receptors and target sites - Surface Receptors/Target
Sites: Receptor sites present on both host (Receptor) and bacterial
surfaces (Adhesins)
- Adhesins: Bind Specific
Host Receptors; Often involve fimbriae as structural cell component;
Host cell receptors are often sugar moieties; Lectin: Adhesin
specific for polysaccharide target receptor (sugar residues)
- Fimbriae (plural):
Modern term for short, hair-like, protein (pilin) appendages
extending outward from the surface of certain bacteria (formerly
and a.k.a., pili) - Pili (plural);
Pilus (singular): Short, hair-like protein (pilin)
appendages extending outward from the surface of certain bacteria;
Term more properly applied to those organelles (F-pilus)
responsible for bacterial conjugation (transfer of nucleic
acids between closely related strains or species = "bacterial
sex")
- Invasive Factors: Invasins
enable a pathogenic microorganism to enter and spread throughout the cells
and/or tissues of the host body; Specific recognition of receptor sites on
target cells enhances pathogenic advantage
- Degradative Enzymes:
Class of protein capable of catalytic reactions
- Bacterial growth requires
food and energy: Growth is achieved by enzymatic catalysis of catabolic
(breakdown) reactions of host tissues (resulting in tissue damage) linked
to catalysis of anabolic (buildup) reactions in the bacterial cell
- Bacterial and host enzymes both
play roles in the disease process
- Toxigenicity: the ability
of a microorganism to cause disease as determined by the toxin it produces
which partly determines its virulence
- Toxin-like pyrogenic (fever
inducing) cell components (e.g., peptidoglycan and peptidoglycan fragments;
Teichoic acid or lipoteichoic acid of Gram-positive cell wall) - Endotoxin: Complex bacterial
toxin; Lipid A portion of lipopolysaccharide from Gram-negative cell walls;
LPS is composed of Lipid A + Core Polysaccharide + O Antigen (a.k.a., O
polysaccharide side chain) and is released upon lysis of the cell during
infection (FIGURE 3-11); Lipid A component is responsible for endotoxin
activity effects on the host; O side chain is the antigenic portion of the
LPS molecule
- Effects of endotoxin:
Binds to specific receptors on macrophages, B lymphocytes (a.k.a., B
cells) and other cells stimulating production and secretion of acute
phase immunoreactants and lymphokines (e.g., IFN-gamma, IL-1, TNF-alpha,
IL-6, histamine, prostaglandins); Stimulates growth of B cells (mitogenic)
- Lymphocyte: Agranular
leukocyte that is concentrated in lymphoid tissue and is active
in immunological responses in the body, including the production
of lymphokines (cytokines) and antibodies
- Septic shock (sepsis):
Endotoxemia; Endotoxin in the blood; Associated with overwhelming
infection resulting in vascular system failure with sequestration
of large volumes of blood in capillaries and veins; Activation of
the complement and kinin systems and the release of histamines,
prostaglandins, and other mediators may be involved - Fever (Pyrogenicity):
Any elevation of the body temperature above the normal; Functions
to speed up immune reactions and to limit/slow bacterial growth
and multiplication - Leukopenia and
then Leukocytosis: Abnormal reduction in the number (-penia)
of leukocytes in the blood, (specifically a count of 5000 or less
per cubic millimeter) / Abnormal increase in the number (-cytosis)
of leukocytes in the blood, as during hemorrhage, infection, inflammation,
or fever (specifically a count of 12,000 or more per cubic millimeter),
respectively - Activation of alternate
complement pathway: C3a; C5a - Increased vascular permeability
(vasodilation); Decreased peripheral circulation; Decreased perfusion
(blood flow) of blood to major organs
- Petechiae:Round, purple lesions caused by intradermal or submucosal microvascular
hemorrhaging; capillary leakage; microhemorrhage - Hypotension:
Low blood pressure - Shock
- Effects on metabolic
and liver functions
- Decreased iron
- Hypoglycemia:
Abnormally low glucose levels
- Activation of clotting
pathway
- Thrombocytopenia:
Abnormally low numbers of blood platelet - Thrombosis: formation
of blood clot (thrombus) in heart or blood vessel - (DIC) Disseminated
intravascular coagulation: Disorder characterized by a reduction
in the elements involved in blood coagulation due to their utilization
in widespread blood clotting within the vessels; Late stages marked
by profuse hemorrhaging
- Shock: Characterized
by failure of the circulatory system to maintain adequate blood
flow to the vital organs; Symptoms include: Hypotension; Weak pulse;
Rapid and shallow breathing; Low body temperature; CNS (central
nervous system) effects (e.g., nausea) - Death
- Exotoxins: Potent toxic
substance formed and secreted extracellularly by species of certain bacteria;
Genetic control can be encoded either chromosomally, on a plasmid,
or by a lysogenic bacteriophage
- Toxoid: Toxin
that can be altered with formaldehyde to lose physiological toxicity
while retaining antigenicity; used as a vaccine
- Bacterial Cytolysins
(a.k.a., Cytotoxins; Cytolytic toxins; Cytolytic enzymes):
Responsible for hemolysis and tissue necrosis; May be
lethal when administered intravenously
- Three major types
based on mechanism of action:
- Hydrolyze membrane phospholipids(e.g., phospho-lipases of Clostridium, Staphylococcus)
- Thiol-activated cytolysins
(oxygen-labile) alter membrane permeability by binding to cholesterol;
e.g., Streptococcus, Clostridium - Detergentlike activity
on cell membranes; e.g. Staphylococcus, rapid rate of lysis
- Two-Component (Bipartite;
Two domain) Toxins (A-B or A-5B): Usually one component
is a receptor-binding domain (B) associated with absorption to
target cell surface and transfer of active component across cell membrane;
Second component is an enzymatic domain (A) (active component)
that enzymatically disrupts cell function
- Conform to general
structural model: Prototype is diphtheria toxin of Corynebacterium
diphtheriae
- Bipartite structure
(B, binding; A, active) - Receptor-mediated
endocytosis (host cell uptake and internalization of exotoxin - ADP-ribosylation
of intracellular target host molecule (e.g., host EF-2 (elongation
factor-2) is ADP-ribosylated by C. diphtheriae exotoxin)
- Other types of exotoxins
(e.g., PA, EF, LF protein toxins of Bacillus anthracis)
- Bacterial Defenses against
Host Responses to Infection
- Encapsulation and antigenic
mimicry, antigenic masking, and antigenic shift are important
bacterial defense mechanisms - Evasion or incapacitation of
phagocytic and/or immune clearance
- Phagocytosis inhibitors:
Mechanisms enabling an invading microorganism to resist being engulfed,
ingested, and or lysed by phagocytes/ phagolysosomes; Patients with
a defective/compromised monocyte-macrophage system (formerly,
RES, reticuloendothelial system)
are particularly susceptible to infection - Capsule (Slime
layer)
- Avoid recognition and killing
- Inhibit opsonization,
chemotaxis, and/or phagocytosis - Inhibit phagolysosomal
fusion and/or resist lysosomal killing - Block activation of
phagocytes by interferon-gamma
- Destroy (lyse) phagocytic
cell
- Inactivate/evade complement
and antibody
- Evade alternate complement
system - Survive opsonization
in presence of complement and PMNs and survive inside phagocytic
cells - Avoid antibody or proteolytically
cleave immunoglobulins
- Avoid immune response by
growing intracellularly
- Direct invasion of cells
- Resist lysosomal enzymes
and antibacterial substances and multiply intracellularly - Escape phagosome; Adapt
to cytoplasmic growth
- Nonspecific T cell activation
and/or mast cell stimulation: Bind TCR on T cell and MHCII on APC without
presence of antigen; Life-threatening release of excess interleukins and
mediators; Toxin-like, autoimmune-like responses or loss of immunoresponsiveness - Induction of excess or chronic
inflammation; Fibrosis (walling-off) of site of infection (e.g., granuloma
formation seen in mycobacterial infections) - Resistance to antibiotics:
Intrinsic resistance; Plasmid-mediated; Chromosomally-mediated
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BSCI 424 — Pathogenic Microbiology
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