Microbial Pathogenicity

Definitions

Infection Process in which a pathogenic organism enters, establishes

itself, multiplies and invades the

normal anatomical barrier of the host; resulting in disease.

Infectious

disease

When infection becomes apparent

results in clinical manifestation.

Colonization Pathogenic organism enters, multiplies but does not invade, and neither causes disease or nor elicits specific immune response. (not same as normal flora).

Infestation Distinct from infection in that it applies specifically to parasites

of macroscopic size, such as

parasitic worms in intestine or arthropods (e.g. lice, itch mite etc.) on the body surface.

Classification of infections

•Primary infection

•Re- infection

•Secondary infection

•Nosocomial infection

•Iatrogenic infection

Classification of infections

Depending on the source of infection

•Endogenous•Exogenous

Classification of infections

Based on the clinical manifestations

•Asymptomatic or in-apparent or subclinical infection

•Symptomatic or apparent infections

•Latent infection

•Atypical infection

Epidemiological Pattern of Infection

Endemic Infections that occur at a

persistent, usually low level in a certain geographical area.

Epidemic Infections that occur at a much higher rate than usual in a

particular geographic area.

Pandemic Infection that spreads rapidly over large areas of the world.

SOURCE AND RESERVOIR OF INFECTION

➢The source of infection refers to the person, animal or object from which a

microorganism is transmitted to the host.

• A reservoir is the natural habitat in which the organism lives and multiplies.

MODES OF TRANSMISSION

Contact transmission

oDirect contact

➢e.g. skin and eye infections and agents of sexually

transmitted diseases

(STD) such as HIV

oIndirect contact through the agency of fomites

➢e.g. face towels shared by various persons may lead to

spread of trachoma.

Inhalation

• Agents causing respiratory infections are acquired by

inhalational route

Air borne

• Droplet nuclei <10µm

➢ Tuberculosis

Ingestion

• Intestinal infections like cholera, dysentery, food poisoning

Inoculation

➢ rabies virus is inoculated directly by bite of a rabid animal.

Blood borne infections

• Hepatitis B, Hepatitis C and HIV may be transmitted by-

oNeedle prick

oBlood

transfusion

Vector borne

• Mechanical vectors

• Biological vectors

Vertical transmission

oTORCH

MECHANISM OF

MICROBIAL PATHOGENICITY

• Pathogenicity - the ability of a microbe to produce disease.

• Virulence - relative degree of pathogenesis (tissue damage)

•Exaltation- Enhancement of virulence

•Attenuation - Reduction of virulence

Bacterial pathogenicity depends

on the following factors

Route of transmission of infection

• Some bacteria, such as streptococci, can initiate infection whatever be the mode of entry.

• Others can survive and multiply only when introduced by the optimal routes.

Eg – Vibrio cholerae through oral route

Infective dose of the organism

• Low Infective dose

oShigella : 10 bacilli

oCryptosporidium parvum : 10 to 30 oocysts

• High Infective dose

oEscherichia coli : 106 - 108 bacilli

oVibrio cholerae : 106 - 108 bacilli

Evasion of the local defences

• Skin, mucus, ciliated epithelium and secretions containing antibacterial substances (e.g.

lysozyme)

Adhesion

• Mediated by

specialized molecules called adhesins which bind to specific host cell receptors

Invasion

• Invasion refers to entry of bacteria into host cells, leading to spread within the host

tissues.

• Eg – Streptococcal infections

Toxins

Endotoxins

• They are the lipid

A portion of lipopolysaccharide- an integral part of the cell wall of Gram negative bacteria.

Biological effects of Endotoxins

• Macrophage activation – fever & inflammation

• Complement activation – fever,hypotension &

shock

• Endothelial activation - vascular perm.

• Coagulation pathways activation - DIC

• Platelet activation - DIC

• Mast cell activation – muscle contraction

• Septicemia – fever , DIC , shock

Exotoxins

• They are heat labile proteins; secreted by certain species of both Gram positive & Gram

negative bacteria and diffuse readily into the surrounding medium.

Toxins (Exotoxins) Mechanism

Staphylococcus

aureus

Enterotoxin

Act as super antigen;

stimulate T cell non-

specifically, to release of

large amounts of cytokines.Toxic shock syndrome

toxin

Corynebacterium

diphtheriae

Diphtheria toxin Inhibits protein

synthesis (by inhibiting

elongation factor-2)

Clostridium

perfringens

α toxin and other major

and minor toxins

Lecithinase and

phospholipase activity →

causes myonecrosis

Clostridium tetani Tetanus toxin

(tetanospasmin)

Decrease in

neurotransmitter (GABA

and glycine) release from

the inhibitory neurons→

spastic paralysis

Differences between endotoxinsand exotoxins

Feature Endotoxins Exotoxins

Nature Lipopolysaccharides Proteins

Source Part of cell wall of Gram

negative bacteria

Secreted both by Gram

positive & negative

bacteria; diffuse into

surrounding medium

Released by Cell lysis

Not by secretion

Actively secreted by the

bacteria

Heat stability Highly stable Heat labile destroyed at

60oC

Mode of action ↑IL-1 and TNF Mostly enzyme like

action

Feature Endotoxins Exotoxins

Effect Non-specific (fever,

shock, etc)

Specific action on

particular tissues

Tissue affinity No Specific affinity for tissues

Fatal dose Only large doses are fatal More potent, even smaller

doses- fatal

Antigenicity Poorly antigenic Highly antigenic

Neutralisation by

antibodies

Ineffective Neutralized by specific

antibodies

Used for vaccine No effective vaccine is

available using endotoxin

Toxoid forms are used as

vaccine; e.g. tetanus

toxoid

Scheme of Microbial Pathogenicity