Principles of microbial

pathogenicity and
epidemiology
Introduction
Some organisms may cause disease through ingestion
of substances (toxins) produced during microbial growth
on foods
Clostridium botulinum botulism
Bacillus cereus vomiting

Number of bacterial cells is associated in the ability of

the bacteria to cause disease
Minimum infective number (MIN) minimum number of
viable organisms required to cause infection
Introduction
Organism must arrive at the portal of entry

Viruses must rapidly gain entry to the host cell

Microbiome
Microorganisms that colonize body surfaces without
causing disease
Bacteria, fungi, protozoa
Develop at birth
Contact with vaginal, fecal, skin

Resident microbiota
Transient microbiota
Microbiome
Mutualism both benefit
Commensalism one benefits without causing harm to
the other

Changes in normal microbiota

(diet change, antibiotic tx, hormonal change, therapy)
Opportunistic pathogens
Reduction of normal flora
Probiotic administration
Portals of Entry

Skin
Respiratory tract
Intestinal tract
Urogenital tract
conjuctiva
Portal of entry (SKIN)
The major part of the body that is widely exposed to
microorganisms

Protective barrier: intact, acid pH

Survivor must compete with the commensal microflora for
grow

Biofilms growth of organisms from the skin

Portal of entry (SKIN)
Mucous membrane presents a much more favorable environment for
microbial growth
(warm, moist and rich in nutrients)
- have own microbiotas / resident flora
- reduces infection: colonization resistance
acidic pH
Circulating antibodies - nonspecific
macrophages / phagocytes

Infection start from direct and indirect contact

Direct infected to non-infected individual, ingestion, inhalation
Indirect inanimate vectors like soil, food, drink, air and airborne particles,
animal vectors(carriers)
Portal of entry (RESPIRATORY
TRACT)
Airborne particles (suspended)

Blanket of mucocilla (protection) URT, nasal cavity

Alveolar macrophages - LRT

A pathogen must avoid being trapped in the mucus and avoid

phagocytosis in the alveolar region

Smoking - increases mucin, decreases ciliated epithelial

cells
Portal of entry (INTESTINAL TRACT)
Extreme acidity and digestive enzymes (protection) - kill
Stomach - commensal flora present
Small intestine
Colon intestinal wall
Layers of mucus
Epithelial cells
Food residue

Pathogen must attach or penetrate the gut wall

Portal of entry (UROGENITAL TRACT)
The bladder, ureters and urethra are sterile

Female are more prone to infection than male

Catheter (mode of infection)

Lactic acid in female inhibits colonization of bacteria

Portal of entry (CONJUNCTIVA)
It is usually free of microoragnisms
Protected by continuous flow of secretions (lachrymal fluid)
Mechanical action of eyelid-blinking

Infection:
Use of contact lens
Damage of conjunctiva
Exposure to chemicals
Reduction of tear flow
Consolidation
A pathogen must be able to survive at its initial portal of entry
Evade normal flora
Evade macrophages & WBCs
Attach to a surface (biofilm)
Adhesive substances mucopeptides, mucopolysaccharide layer
Pili
agglutinins

Factors for Bacterial Multiplication:

Organisms growth rate
Initial number at the site
Ability to resist immune response
Consolidation
Virulence: The ability of an agent of infection to
produce disease

Nutrient acquisition, trace elements (Fe)

Siderophores greater affinity to Fe
Hydrolytic enzymes Fe release (host)
Biofilms
Resistance to host defense
Avoidance of phagocytosis
Presence of slime / capsule surrounding the cell wall
M-protein of streptococci
Polysaccharide capsule of pneumococci
K-antigen - E. coli

Avoidance of opsonization
process of identifying the organism to the phagocyte
Protein-A (S. aureus)
Survival following phagocytosis
Microorganism can survive following phagocytosis when
it avoids the killing and digestion process within the
phagocyte
Kill phagocyte - production of leucocidins - (lysosomal
substances)

Lifespan of phagocytes are short

Manifestation of disease
The course of bacterial infection can proceed in a number of ways
Can be related to the ability of the organism to penetrate and invade
surrounding tissues and organs

Non-invasive Pathogens
Production of toxins
Partially invasive Pathogens
Attach to mucosal epithelia and penetrate rapidly into the epithelial cells

Fully invasive pathogens

Active spread pathogens aggressively invade the tissues at the primary
site of infection
Passive spread pathogens are transported around the body in the blood,
CSF, and other fluids
Fully invasive pathogens (active
spread)
Haemolysin have lytic effect on red blood cells, releasing iron
containing nutrients
Fibrinolysin activate plasminogen to dissolve fibrin clots
(prevents healing of wounds, spread of infection)
Collagenases and hyaluronidases dissolves collagen fibers
and hyaluronic acids that function as intracellular cements.
Thus causing tissue break up
Phospholipases damage tissue cells by hydrolysing
phospholipids
Fully invasive pathogen (passive
spread)
Damage of the blood vessels

Spread of infection through the blood stream

Bacteremia

When invading organisms cross the epithelial barrier

and carried in the lymphatic ducts (immune system)
Damage to tissues (Direct damage)
Specific effects the damage caused by the organism to the tissue or
organ has specific effect

Example: Clostridium tetani causes tissue necrosis and lockjaw

Streptococcus pyogenes Scarlet fever (skin rash)

Non-specific effects if the infective agent damages an organ and

affects its functioning

Example: Vibrio cholerae diarrhea (results to water loss and electrolytes)

Kidney Malfunction
Clostridium botulinum
Bacillus cereus
Damage to tissues (Indirect
damage)

Reactions of the body manifested: signs and

symptoms
inflammation
elevated body temperature
aching joints/body pains
Recovery from infection
(exit of microorganism)
Exit of microorganism (to infect other individual)

control the multiplication of the infective agent

Complete destruction of the organism and restoration of

a sterile tissue
Epidemiology of Infectious Disease
Public Health / Community Health

Prevention
Spread of infectious disease in a population of individuals

Involve the whole community

Eradication of the source of infection
Outbreak prevention
Factors for Outbreak:
F- number of susceptible individuals
I infectivity of the agent
P population density

Vaccination programs
BIOFILMS
Introduction
Bacteria that exist as adherent microcolonies (biotic/abiotic
surfaces)

approx 60% of human infections

Chronic, recurrent, device related infections
Formed to maintain and not to be washed away
Provide a more secure environment for sustainability (phagocytosis difficult)

As biofilm, bacteria and fungi are less susceptible to

antimicrobials, they become more tolerant
Biofilms in Food industry
Biofilms formed on the hard surfaces of food processing
plants
Resist many biocides
Ex. Tables, knives, processing equipment
Biofilms and medical devices
Medical device-associated infection microbial
colonization and biofilm formation
Indwelling catheters, endotracheal tubes, joint
prostheses, surgical sites
complete removal and replacement of device

Nosocomial infections
Tolerance of biofilms to
antimicrobials
Advent of antibiotics
Antibiotic resistant strains of bacteria
Lack of responsiveness to antimicrobial therapy
Recurrent UTIs
For antibiotic to be effective requires 1000x more
concentration which is not safe to patients
Adaptation of biofilm - Altered tolerance to drugs
Only in biofilm mode and not in planktonic mode
Mechanisms of biofilm tolerance
- Compact and highly charged matrix surrounding the
biofilm
(prevents penetration of antibiotics)
- Charge of antibiotic affects penetration
Not highly charged antibiotic easily penetrate the matrix
Highly charged antibiotic delayed penetration

- Channels: nutrients transfer; waste diffusions

Persister cells

- Biofilms that pre-exist in the population

- Biofilms come in several species but may also come in single sp.
- Survive but not grow in the presence of selective agents

Quorum Sensing (QS) - Key regulatory process associated with biofilm

formation
-allows cells to live in close proximity, facilitating intercellular
communication
Insurance Hypothesis

- Diverse population found in the biofilm

- population will survive the stress of antimicrobial challenge
- increases toxins in nature
Treatment of Biofilm Infections

Better use of existing antimicrobials

- Antibiotic combination (synergies)
- bioFILM PA assay
- Education on antibiotic fermentation

Next generation antimicrobials

- derived from microbial life form (nature)
- synthesis of antibiotics
The End