virulence by dr shireen rafiq (rmc)

BACTERIAL VIRULENCEDr Shireen Rafiq

MBBS, M.Phil, Ph.D

Koch’s PostulateKoch’s Postulateisolated isolated

diseased not healthy peoplediseased not healthy peoplegrowthgrowth

pure culturepure cultureinduce disease induce disease

susceptible animalssusceptible animalsre-isolated re-isolated

susceptible animalssusceptible animals

Normal flora

Resident ------commensals

TransientCarrier stateColonization

A pathogen is a microorganism that is able to cause disease in a plant, animal or insect.

Pathogenicity is the ability to produce disease in a host organism.

Microbes express their pathogenicity by means of their virulence=the degree of pathogenicity.

Infectious dose depends on virulence factors

ROUTES OF ENTRY

Host defensesHost defensesGutGutperistalsis peristalsis defecation defecation

respiratory tract respiratory tract ciliary action ciliary action coughingcoughingsneezingsneezing

urogenital tract urogenital tract urination urination

MICROBESPathogens Opportunistic Pathogens Obligate Pathogens Symbiosis: Mutualism Parasitism Commensalism

PEPTIDOGLYCAN

CAPSULE/BIOFILMS

PILI

FIMBRIA

LIPOTECHOIC ACID

PLASMIDS

VACUOLE FORMATION (in Host)

HYDROPHOBIC MOLECULES

TOXINS (Exotoxin and Endotoxin)ENZYMES

SIDEROPHORES (ferric ions)

STRUCTURAL

NON STRUCTURAL

ADHERENCE FACTORSAdhesin/Ligand: A surface structure or macromolecule

that binds a bacterium to a specific surface. Receptor: A complementary macromolecular binding

site on a (eucaryotic) surface that binds specific adhesins or ligands

Biofilms: protect bacteria from antibiotics and host defense resulting in chronic wound infections

Vs INFECTION

E. coli with fimbriae

Factors Facilitating PathogenesisADHESINSANTIPHAGOCYTIC FACTORS -CAPSULE -M PROTEIN -CYTOTOXINSURVIVAL WITHIN PHAGOCYTES (PREVENTION OF)

-OXID. BURST -FUSION AND DEGRANULATION -LYSOZYMES -ESCAPE FROM PHAGOSOMES SIDEROPHORESTOXINS AND ENZYMESPLASMIDS

Toxigenesis is the ability to produce toxins.

Exotoxins (gram positive and gram negative) secreted by bacteria, polypeptide

Endotoxins (gram negative ) part of cell wall, lipopolysaccharide.

A-B toxinsA-B toxins

ActiveActiveBindingBinding

AA

Cell surfaceCell surface

BB

• ProteasesProteases • PhospholipasesPhospholipases• Detergent-like actionDetergent-like action

Membrane damaging exotoxins

EXOTOXIN ENDOTOXIN1. EXCRETED INTEGRAL

2.GRAM POSITIVE AND NEGATIVE

GRAM NEGATIVE

3. POLYPEPTIDE LIPOPOLYSACCHARIDE

4. UNSTABLE/DESTROYED ABOVE 60C

STABLE ABOVE 60C

5. HIGHLY ANTIGENIC Toxoid formation

WEAKLY ANTIGENIC

6. HIGHLY TOXIC (ug) MODERATELY TOXIC (mgs)7. BIND TO RECEPTORS RECEPTORS NOT INVOLVED8. NOT PYROGENS PYROGENIC9. PLASMID OFTEN INVOLVED CHROMOSOMAL

EFFECTS OF ENDOTOXIN Lipid A

FeverShockStimulation of immune systemGreater susceptibility to stressLethality

Stages of infectious diseaseIncubation period

Prodromal period

Specific illness period

Recovery period

MUTATIONSChange in the base sequence of DNA resulting in

altered phenotype. Mutations result from three type of molecular changes

1 Base substitutions2 Frameshift mutation3 Transposons or insertion sequenceChemicals , radiations and viruses

TRANSDUCTION

RECOMBINATIONHomologous

Non homologous

different endonucleases and ligases are involved