Chapter 15 Microbial Mechanisms of Pathogenicity

Disease

Disease

a condition where normal structure and/or function are damaged or impaired

Infection

invasion of pathogen or parasite that lead to disease

Signs

things that can be directly measured by clinician (e.g. blood cell counts)

Symptoms

things felt by patient that cannot be clinically measured (e.g. nausea)

Syndrome

groups of signs & symptoms that help indicate a particular disease

Signs & symptoms help direct

diagnosis

Some patients are asymptomatic/subclinical

only signs can be observed thru correct testing

Infectious

disease caused by direct effect of a pathogen

Communicable

capable of spreading person-to-person (contagious – easily spread)

Iatrogenic

acquired as result of medical procedure

Nosocomial

acquired from hospital setting

Zoonotic

acquired from animal

Non-communicable

obtained from non-living thing such as soil or contaminated object

Non-infectious

not caused by pathogen

Malaria is

Communicable • Infectious • Zoonotic

Sickle cell anemia is

Non-communicable • Non-infectious (genetic)

Incubation

initial entry of pathogen; replication begins

Prodromal

Replication continues; host shows signs & symptoms

Illness

signs & symptoms are most severe in host

Decline

pathogen no. start to decrease; host’s immune system is weak and vulnerable to secondary infection

Convalescence

host starts to recover

Acute disease

relatively short (hours, days, week)

Chronic disease

longer time (months, years, lifetime)

Latent disease

comes in episodes; pathogen replicates when disease is active

Kochs Postulates step 1

The suspected pathogen must be found in every case of disease and not be found in healthy individuals

Kochs Postulates step 2

The suspected pathogen can be isolated and grown in pure culture

Kochs Postulates step 3

A healthy test subject infected with the suspected pathogen must develop the same signs and symptoms of disease as seen in postulate 1

Kochs Postulates step 4

The pathogen must be r-isolated from the new host and must be identical to the pathogen from postulate 2

( General) Koch’s Postulates

Set of standards that must be met to demonstrate that X pathogen causes X disease and developed 1884 and still used today

Pathogenicity

ability of pathogen to cause disease

Virulence

degree of pathogenicity

Koch’s (wrong) assumptions

1. Pathogens are found only in disease individuals

2. All subjects are equally susceptible to infection

3. All pathogens can be grown in culture

Median infectious dose (ID50) –

no. of pathogens required to infect 50% of those inoculated

Median lethal dose (LD50)

no. of pathogens required to kill 50% of those infected

Primary pathogen:

can cause disease in a host regardless of host’s resident microbiota or immune system

Opportunistic pathogen:

can only cause disease in situations that compromise the host’s defenses (e.g. protective barriers, immune system, or normal microbiota)

Exposure (or contact) can occur in many ways:

pathogens must be exposed to portals of entry to begin adhesion

TORCH infections

pathogens that can cross placental barrier as portal of entry

Adhesins

molecules/structures that bind to certain host receptors

proteins that aid in attachment to host cell receptors

Biofilm

production of community glycocalyx

Invasion

occurs when colonization is established

Intracellular pathogens invade

via endocytosis and evasion of host immune defenses

Multiplication leads to

established host infection

Local infection

small area of body

Focal infection

pathogen or toxin spreads to secondary location

Systemic

occurs throughout body (ex. septicemia)

Primary infections

can lead to secondary infection of different pathogen

Persistence requires transmission to a new host through a

portal of exit

Virulence factors

pathogen product that assists in ability to cause infection and disease

Examples of Virulence factors are

Adhesion factors • Exoenzymes • Toxins •Immune evasion

Exoenzymes

extracellular enzymes used to invade host tissues

Exoenzymes types

glycohydrolases, nucleases, phospholipases, proteases

Glycohydrolases function

Degrades hyaluronic acid that cements cells together to promote spreading through tissues (Staphylococcus Aureus)

Nucleases Function

Degrades DNA released by dying cells that can trap the bacteria, thus promoting spread (S.Aureus)

Phospholipases Function

Degrades phospholipid bilayer of host cells, causing cellular lysis and degrade membrane of pathogens to enable escape into the cytoplasm (Bacillus anthracis)

Proteases function

Degrades collagen in connective tissue to promote spread (Clostridium Perfingens)

Toxins

biological poisons that assist in ability to invade and cause tissue damage (toxigenicity

Endotoxins

lipopolysaccharides that triggers host inflammatory responses; can cause sever fever and shock

Exotoxins

proteins mostly produced by Gram (+); Targets receptors on specific cells

Limulus amebocyte lysate (LAL) Test

blood cells of the horseshoe crab mixed with patient’s serum; observed chromogenically or by coagulation

ELISA

enzyme-linked immunosorbent assay: uses antibodies to detect endotoxins

A region is

active

B region is

binding

Intracellular targeting

with A & B regions for activity and binding; Ex. diphtheria & botulinum toxin

Membrane-disrupting

phospholipases that degrade bilayer membrane; Ex. Bacillus anthracis & Rickettsia spp.

Superantigen

trigger excessive production of cytokines by immune cells;

Host evasion

mechanisms to evade phagocytosis

Hemolysins and Leukocidins: can target

RBC, WBC, and other cells

Antigenic drift

result of point mutations causing slight changes in spike proteins (H & N)

Antigenic shift

major change in spike proteins due to gen reassortment

Host evasion examples

Capsules that enlarge bacterial cell so phagocytes cannot engulf pathogens

• Proteases digest host antibody molecules

Mycotoxins (fungi)

produced by Claviceps purpurea and Aspergillus spp. that contaminate grains & other staple crops

(Protozoa) Giardia lamblia uses

adhesive disk of microtubules to attach to intestines

Plasmodium falciparum quickly changes adhesive protein for RBCs to avoid immune recognition; causes chronicity in malaria patients. This is an example of

Antigenic variation

“Glycan gimmickry” (helminths)

mimic host cells to evade immune system

Roundworms produce

cuticle to last longer against host defense assaults

Schistosoma mansoni

degrades host antibodies to halt immune defense

Tissue penetration is

commonly achieved w/ proteases

When can patients be contagious?

During the prodromal period

EHEC

Enterohemorrhagic E. coli

Molecular Koch’s Postulates

Identifies gene instead of pathogen

Molecular Koch’s Postulates limitations

1. genetic manipulation of some organisms isn’t possible with current techniques

2. some diseases do not have suitable animal models

Drugs, resident microbiota, genetics, age can all influence

susceptibility to disease

Stages of Pathogenicity

1. Exposure to host

2. Adhesion

3. Invasion

4. Infection

5. Transmission

Adhesion is

Pathogens have varying capability of colonization