Microbial Pathogenesis

HINDOL MAITY / DR GUNJAN

DEPT. OF MICROBIOLOGY, MGIMS SEVAGRAM
Concept

 Ability of bacteria to produce disease or tissue injury

 Closely related term (but not similar) – Pathogenicity and Virulence
 Pathogenicity: Ability of microbial species to produce disease
 Virulence: The relative degree of pathogenesis (tissue damage), which varies between
strains of same species depending upon expression of virulence factors
 Relative term
 Virulence of a strain may undergo spontaneous or induced variation
 Exaltation: Enhancement of virulence
 Attenuation: Reduction of virulence using multiple methods
Route of transmission

 Crucial for microbes

 Eg1: Streptococci can initiate infection through
multiple route of entry
 Eg2: Vibrio cholerae can infect only orally
 Ability to cause tissue damage and establish
themselves
Site Major Local Defense(s) Basis for Failure of Local Defense Pathogens (Examples)
Skin Epidermal barrier Mechanical defects (punctures, burns, Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa
ulcers)
Needle sticks Human immunodeficiency virus, hepatitis viruses
Arthropod and animal bites Yellow fever, plague, Lyme disease, malaria, rabies
Direct penetration Schistosoma spp.
Gastrointestinal Epithelial barrier Attachment and local proliferation of Vibrio cholerae, Giardia duodenalis
tract microbes
Attachment and local invasion of microbes Shigella spp . , Salmonella spp., Campylobacter spp.
Uptake through M cells Poliovirus, Shigella spp., Salmonella spp.
Acidic secretions Acid-resistant cysts and eggs Many protozoa and helminths
Peristalsis Obstruction, ileus, postsurgical adhesions Mixed aerobic and anaerobic bacteria ( Escherichia
coli , Bacteroides spp.)
Bile and pancreatic enzymes Resistant microbial external coats Hepatitis A, rotavirus, norovirus

Normal protective microbiota Broad-spectrum antibiotic use Clostridioides difficile

Respiratory tract Mucociliary clearance Attachment and local proliferation of Influenza viruses
microbes
Ciliary paralysis by toxins Haemophilus influenzae , Mycoplasma pneumoniae , Bordetella pertussis
Resident alveolar Resistance to killing by phagocytes Mycobacterium tuberculosis
macrophages
Urogenital tract Urination Obstruction, microbial attachment, and Escherichia coli
local proliferation
Normal vaginal microbiota Antibiotic use Candida albicans
Intact epidermal/epithelial Microbial attachment and local Neisseria gonorrhoeae
barrier proliferation
Direct infection/local invasion Herpes viruses, syphilis
Local trauma Various sexually transmitted infections (e.g., human papillomavirus)
Infective dose

 Minimum inoculum size that is capable of  Dependent on

initiating an infection  Virulence of the microbe
 Low infective dose:  Host’s age and immune status
 Shigella- very low (10 bacilli)  Ability of microbe to survive first line of
 E coli O157:H7 (<10 bacilli) defences
 Campylobacter jejuni (500 bacilli)  Shigella can survive in acidic environment,
whereas Vibrio is acid labile
 Large infective dose:
 E coli- 106 – 108 bacilli
 Salmonella- 102 – 105 bacilli
 Vibrio cholerae- 106 – 108 bacilli
Adhesion

 An initial event of adhesion to body surfaces  Fimbrae or Pili:

 Most important adhesin for bacteria
 Mediated by specialized molecules called
 Directly bind sugar residues (glycolipids or
adhesins that binds to specific host cell
glycoproteins) on host cells
receptors
 Non-pilus adhesins:
 Adherence prevents the bacteria from being  M protein (Strep. pyogenes)
flushed away
 Lipoteichoic acid (GPC)
 Cell surface lectin (Chlamydia)
 Biofilm production:
 Group of bacterial cells stick to each other on a surface
and are embedded inside slime layer of self-produced
matrix of extracellular glycocalyx
Invasion

 Entry of bacteria into host cells  Important virulence factors:

 Highly invasive bacteria produce spreading or  Virulence marker antigen or invasion plasmid
generalized lesions (eg. Streptococcal antigen in Shigella
infection)  Enzymes: Hyaluronidase, collagenase,
 streptokinase, IgA proteases
Less invasive bacteria cause localized lesions
(eg. Staphylococcal abscess)
 Some pathogens remain confined and let the
toxin in (eg. Clostridium tetani)
Intracellular survival

Mechanism used by bacteria for

Intracellular bacteria intracellular survival
Facultative Obligate intracellular Mechanism of Organism
intracellular bacteria intracellular survival
Salmonella typhi, M leprae Inhibition of Legionella
Brucella, Legionella, Rickettsia phagolysosome fusion M tuberculosis
Listeria, Nocardia, Chlamydia Chlamydia species
Neisseria meningitidis, Coxiella burnetti Resistance to lysosomal Salmonella
Yersinia, M tuberculosis enzymes typhimurium
Coxiella sp
M leprae
Adaptation to Listeria, Rickettsia,
cytoplasmic replication Francisella tularensis
Antiphagocytic Factors

 Capsule: Prevents the phagocytes (neutrophils and macrophages) from adhering to bacteria
 N meningitidis
 S pneumoniae
 H influenzae
 K pneumoniae
 Cell wall proteins: help in invasion
 Protein A of S aureus binds to IgG and prevents compliment activation
 M protein of S pyogenes
 Cytotoxins
 Interfere with chemotaxis or killing of phagocytes (S aureus produce hemolysins & leukocidins that lyse and
damage RBCs and WBCs)
Toxins

 Endotoxins  Endothelial activation: High vascular

 Lipid A portion of Lipopolysaccharide (LPS) permeability
 Present in integral of cell wall on Gram-negative  Coagulation pathway activation: Hageman
Bacteria factor
 Released by natural lysis  Platelet activation
 Responsible for various biological effects of host  Mast cell activation: Histamine
 Macrophage activation: Interleukin 1, TNF α,  In Gram-negative septicemia: Shock and
Nitric oxide, T & B cell
death
 Complement activation: Alternative pathway –
release C3a & C5a
Toxins

 Organisms Exotoxins
Exotoxins
Staphylococcus aureus Enterotoxin, TSS toxin
 Heat labile proteins; secreted by certain Gram-
Positive and Gram-Negative bacteria and diffuse Streptococcus pyogenes Pyrogenic exotoxin
readily Corynebacterium diphtheriae Diphtheria toxin
 High potency: Minute amount (39.2gm of Bacillus anthracis Anthrax toxin
Botulinum toxin may eradicate entire Clostridium perfringens α toxin
humankind!!)
Clostridium tetani Tetanus toxin
 Used for vaccine: Converted to toxoids (treating
C botulinum Botulinum toxin
with formaldehyde) – lack toxicity but antigenicity
Diarrheagenic E coli Heat labile toxin; Heat stable toxin;
intact Verocytotoxin
 Specific action: Highly specific to target tissue Shigella dysenteriae type 1 Shiga toxin

(tetanus toxin to CNS only) Vibrio cholerae Cholera toxin

Pseudomonas Exotoxin A
Difference between Endo and Exo (TOXINS)

Feature Endotoxins Exotoxins

Nature Lipopolysaccharides Proteins
Source Part of cell wall of Gram Negative bacteria Secreted by both Gram Positive and Gram
Negative – diffuse into surrounding medium
Released by Cell lysis; not by secretion Actively secrete by bacteria
Heat stability Highly stable Heat labile; destroyed at 60 °C
Mode of action ˄IL 1 and TNF α Mostly enzyme like action
Effect Nonspecific (Fever, shock) Specific action on particular tissues
Tissue affinity No Yes
Fatal dose Large amount More potent; small dose
Antigenicity Poorly antigenic Highly antigenic
Neutralization by antibodies Ineffective Neutralized by specific antibodies
Vaccine usage Not used Toxoid forms (eg. Tetanus toxoid)
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