Pathogenic Factors

The microbe:
Few are pathogenic
Many benefit the host and do not cause disease
Human body: 10 trillion cells + 100 trillion bacterial cells

The host:
Host factors greatly influence the relationship between microbe and host

One organism benefits from the relationship

ex: Saprophytic mycobacteria of the ear and external genitals
- live on secretions and sloughed-off cells causing no benefit or harm to the host (eat dead cells)

Both organisms benefit from the relationship

ex: Escherichia Coli in large intestine synthesize Vitamin K - vitamin K is absorbed into the blood stream and is used by the host
- large intestine of the host provides nutrients used by the bacteria, facilitating their survival

One organism benefits from the relationship at the expense of the other
- direct harm to host
- causes infectious disease

they do not produce disease under normal conditions
- Resident microbiota permanently colonize the host
- Transient microbiota temporarily colonize the host

commensal/mutualistic relationship

nutrients
physical + chemical factors
mechanical factors
other "host" factors

secretory + excretory products of cells, bodily fluids and food in the GI tract drive what type of bacteria grow in which part of the body

- temperature
- pH
- o2, co2
- salt
- sunlight

Chewing

Flow of saliva and peristalsis of GI tract

Mucous and ciliary action of resp system

Bacteria must have adhesives to hold on to epithelial cells

Age
Nutritional status
Disability
Stress
Hygiene
Lifestyle - travelling
Geography
Occupation

normal flora benefits the host by preventing growth of pathogenic microbes

Competes with the pathogen for nutrients

Produces substances harmful to the pathogen
- directly competes with pathogens

Manipulates the host environment - increases or decreases pH
- increases or decreases O2 levels

E. Coli (escherichia coli)
- produces bacteriocins
- bacteriocins are proteins that inhibit the growth of closely related species of bacteria such as Salmonella and Shigella species

ex: microbial antagonism fails

RESULT: infection/disease

HOW?
age
antibiotic use
changes in hygiene
nutritional status

C. Diff

- causes range of GI symptoms, from mild diarrhea to severe, even fatal colitis

- growth inhibited by normal flora in L intestine

Antibiotic mediated destruction of the GI normal flora creates an environment conducive to C. diff growth, resulting in disease

an infection which the parasite takes advantage of host weakness: immune suppressed, changes in normal microorganisms (antimicrobial treatment), or the normal microbiota but at different location (E. coli and UTI's)

1. microbes from host normal flora move from their normal habitat, causing disease
- E Coli gaining access to other body sites like urinary tract causing UTI

2. host's immune system is weakened/compromised
- pneumocystis jirovecii causes pneumonia in the immunocompromised patient, but has no effect on healthy individuals

3. changes occur in composition of host's normal flora:
- shift in the relative abundance of microbes (due to antibiotic therapy) creates opportunity for one species to thrive and cause disease

Contact/exposure: - bump into something to be exposed to it
- must be in contact with it

Adherence
- adhere to tissues

Evasion of host defenses and penetration
- if body can fight it, it will, before infection starts

Damage of host cells
- result of infection - sneezing, coughing, vomiting to move on to next host

Transmission

1. mucous membranes
- conjunctiva, upper resp tract
- GI tract
- GU tract

2. skin
- when unbroken it is impenetrable
- bacteria gain access thru natural openings (follicles, sweat glands)

3. direct deposition beneath mucous membranes or skin
- trauma (punctures, wounds, cuts), surgery, invasive procedures

- how pathogen attaches itself to host tissues at entry
- accomplished by "adhesins" binding specifically to surface 'receptors' located on the cells of host tissues

bacterial structures (fimbriae, flagella)

adherence proteins (M proteins)

glycocalyx (capsule, slime layer)

adhesions on fimbriae and flagella of bacteria

ex: P-fimbriae on pyelonephritogenic E coli adhere to a specific galactose disaccharide found on the surface of uroepithelial cells, responsible for 90% of all UTI's

M proteins produced by streptococcus pyogenes (GAS); appear as hair-like projections from the cell surface - mediates attachment of bacteria to epithelial cells of the host - many subtypes, some more strongly associated with specific diseases than others

"capsule" if well organized and attached to cell wall
- K1 capsule associated with strains of Neisseria meningitidis type B
- Binds to epithelial cells of the ventricles and vascular endothelium of the brain, causing meningitis

unorganized and loosely attached to cell wall
- facilitates formation of biofilms

Colony of bacteria that adheres to surfaces (living and nonliving), embedded in an extracellular slime layer

surfaces: teeth, medical catheters, heart valves, hip replacement components, contact lenses, industrial food equipment

May be many layers and contain many species

Involved in chronic infections

Highly resistant to disinfectants and antibiotics


Shelters microorganisms from host defences

few available
surgical intervention often required

enzymatic bacteriophage: virus that infects bacteria
- digests slime layer easily

Impairs phagocytosis preventing phagocytic cell from adhering to the microbe, thereby increasing the virulence of the pathogen

With time, the host will produce antibodies against the capsule

Important for adherence and evading host defenses

M proteins increase virulence by helping bacteria resist phagocytosis by WBC

ex: streptococcus pyogenes

Mycolic acid present in cell wall of Mycobacterium tuberculosis increases virulence by resisting digestion by phagocytosis

enzyme produced to coagulate fibrinogen in the blood to form fibrin

fibrin clot protects the bacteria from phagocytosis and isolate microbe from other host defenses

produced by some staphylococci spp.

enzyme that degrades fibrin --> digests clot that isolate wounds and are created by bacteria as protection from phagocytosis

streptokinase produced by streptococcus pyogenes

staphylokinase produced by staphylococcus aureus

facilitate a microbe's ability to evade host defenses

kinase also facilitates a microbe's entry to host tissues

able to survive phagocytosis, grow and reproduce within the immune cells, shielded

Escaping phagosomes before fusing with host cell lysosomes

Preventing phagosomes-lysosome fusion

Reducing effectiveness of toxic compounds within lysosome

Producing cell walls resistant to lysosomal proteases

Degrades hyaluronic acid, a polysaccharide that holds host cells together

Allows bacteria to penetrate into host tissues (gap between cells)

an enzyme that breaks down collagen + allows bacteria to move deeper in host

deeper = few immune cells, no flora, more robust infection

salmonella spp. and E coli spp. produce invasins that rearrange actin filaments in epithelial cells of the intestinal lumen

disruption of cytoskeleton induces "membrane ruffing" of the host cell; bacteria sinks into the ruffle and is engulfed by the host cell

Once inside host, bacteria becomes enclosed in a vesicle and induces an inflammatory response

Can move from the epithelial cell into the blood stream or enter phagocytes where they reproduce and grow

Appropriating host nutrients

Causing direct damage to tissues surrounding site of invasion

Producing toxins

Inducing hypersensitivity reactions (allergy)

iron: required for growth of bacteria
- tightly bounded to iron transport proteins in humans
- low availability = microbial iron deficiency

siderophores: bind to iron more tight than host transport proteins

direct binding to host iron binding proteins

producing toxins: bacterial toxins kill host cells, releasing iron stores of the host; pathogen acquires iron via receptor binding

As intracellular bacteria and viruses metabolize and multiply in host cells, the host cell typically ruptures to facilitate their release, destroying the host cell

Once released, pathogens spread to other tissues in great numbers

Some pathogenic bacteria produce toxins that alter the normal metabolism of host cells


toxins inhibit protein synthesis, destroy blood cells and blood vessels, disrupt NS function

Enzymatic proteins produced inside some living pathogenic bacteria as a normal part of growth and metabolism

Secreted into the surrounding environment, or released during cell lysis

Soluble in bodily fluids and rapidly transported throughout the host; highly toxic in nature, exposure can be fatal

made by gram pos and neg bacteria

caused by the effect of the toxin on host cells, not the pathogen itself
- ingestion/exposure to the toxin is sufficient to produce disease

- botulism and staphylococcal food poisoning both caused by ingesting an exotoxin

consist of A & B polypeptides,

A = active enzymatic component and
B = binding component

bordetella pertussis
- toxin increases cAMP in resp epithelial cells, causing increased mucus production and coughing

induce cell lysis via formation of protein channels (leukocidins, hemolysins) or disruption of phospholipid layer of cell membrane (phospholipases)

released when gram neg bacteria are killed (or multiply); cell wall lyses, liberating the endotoxin

stimulate macrophages to release high conc of IL1

all endoxotins produce same S/S regardless of pathogen: chills, fever, weakness, aches

increased tissue factor: activates extrinsic + intrinsic coagulation cascade
- DIC: obstructive clots in capillaries, inducing tissue death, shock and death of host in severe cases

1. macrophage ingests gram neg bacterium

2. bacterium is degraded in a vacuole, releasing endotoxins that induce macrophage to produce IL1

3. IL1 released by macrophage into bloodstream, thru which it travels to hypothalamus of the brain

4. IL1 induces hypothalamus to produce prostaglandins which rest body's thermostat to higher temp, producing fever

specific portals of exit in secretions, excretions, discharges or shed tissue

GI tract
GU tract
resp tract
skin, conjunctiva, blood