Principles of microbial

pathogenicity and epidemiology

Introduc8on
Some organisms may cause disease through inges2on of substances
(toxins) produced during microbial growth on foods
Clostridium botulinum botulism
Bacillus cereus vomi2ng

Number of bacterial cells is associated in the ability of the bacteria to
cause disease
Minimum infec2ve number (MIN) minimum number of viable
organisms required to cause infec2on
Introduc8on
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 benet
Commensalism one benets without causing harm to the other

Changes in normal microbiota
(diet change, an2bio2c tx, hormonal change, therapy)
Opportunis2c pathogens
Reduc2on of normal ora
Probio2c administra2on
Portals of Entry

Skin
Respiratory tract
Intes2nal tract
Urogenital tract
conjuc2va

Portal of entry (SKIN)
The major part of the body that is widely exposed to microorganisms

Protec2ve barrier: intact, acid pH

Survivor must compete with the commensal microora for grow

Biolms 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 ora
- reduces infec2on: coloniza2on resistance
acidic pH
Circula2ng an2bodies - nonspecic
macrophages / phagocytes

Infec2on start from direct and indirect contact

Direct infected to non-infected individual, inges2on, inhala2on
Indirect inanimate vectors like soil, food, drink, air and airborne par2cles, animal

vectors(carriers)
Portal of entry (RESPIRATORY TRACT)
Airborne par2cles (suspended)

Blanket of mucocilla (protec2on) 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 diges2ve enzymes (protec2on) - kill
Stomach - commensal ora present
Small intes2ne
Colon intes2nal wall
Layers of mucus
Epithelial cells
Food residue

Pathogen must aXach or penetrate the gut wall
Portal of entry (UROGENITAL TRACT)
The bladder, ureters and urethra are sterile

Female are more prone to infec2on than male
Catheter (mode of infec2on)

Lac2c acid in female inhibits coloniza2on of bacteria

Portal of entry (CONJUNCTIVA)
It is usually free of microoragnisms
Protected by con2nuous ow of secre2ons (lachrymal uid)
Mechanical ac2on of eyelid-blinking

Infec2on:
Use of contact lens
Damage of conjunc2va
Exposure to chemicals
Reduc2on of tear ow
Consolida8on
A pathogen must be able to survive at its ini2al portal of entry
Evade normal ora
Evade macrophages & WBCs
AXach to a surface (biolm)
Adhesive substances mucopep2des, mucopolysaccharide layer
Pili
agglu2nins

Factors for Bacterial Mul2plica2on:

Organisms growth rate
Ini2al number at the site
Ability to resist immune response
Consolida8on
Virulence: The ability of an agent of infec2on to produce disease

Nutrient acquisi2on, trace elements (Fe)

Siderophores greater anity to Fe
Hydroly2c enzymes Fe release (host)
Biolms
Resistance to host defense
Avoidance of phagocytosis
Presence of slime / capsule surrounding the cell wall
M-protein of streptococci
Polysaccharide capsule of pneumococci
K-an2gen - E. coli

Avoidance of opsoniza2on
process of iden2fying the organism to the phagocyte
Protein-A (S. aureus)
Survival following phagocytosis
Microorganism can survive following phagocytosis when it avoids the
killing and diges2on process within the phagocyte
Kill phagocyte - produc2on of leucocidins - (lysosomal substances)

Lifespan of phagocytes are short
Manifesta8on of disease
The course of bacterial infec2on can proceed in a number of ways
Can be related to the ability of the organism to penetrate and invade surrounding
2ssues and organs

Non-invasive Pathogens
Produc2on of toxins
Par7ally invasive Pathogens
AXach to mucosal epithelia and penetrate rapidly into the epithelial cells
Fully invasive pathogens
Ac2ve spread pathogens aggressively invade the 2ssues at the
primary site of infec2on
Passive spread pathogens are transported around the body in the
blood, CSF, and other uids

Fully invasive pathogens (ac8ve spread)
Haemolysin have ly2c eect on red blood cells, releasing iron containing
nutrients
Fibrinolysin ac2vate plasminogen to dissolve brin clots
(prevents healing of wounds, spread of infec2on)
Collagenases and hyaluronidases dissolves collagen bers and hyaluronic acids
that func2on as intracellular cements. Thus causing 2ssue break up
Phospholipases damage 7ssue cells by hydrolysing phospholipids
Fully invasive pathogen (passive spread)
Damage of the blood vessels

Spread of infec2on through the blood stream

Bacteremia

When invading organisms cross the epithelial barrier and carried in
the lympha2c ducts (immune system)
Damage to 8ssues (Direct damage)
Specic eects the damage caused by the organism to the 2ssue or
organ has specic eect

Example: Clostridium tetani causes 2ssue necrosis and lockjaw

Streptococcus pyogenes Scarlet fever (skin rash)

Non-specic eects if the infec2ve agent damages an organ and

aects its func2oning

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

Kidney Malfunc7on
Clostridium botulinum
Bacillus cereus
Damage to 8ssues (Indirect damage)

Reac2ons of the body manifested: signs and symptoms

inamma2on
elevated body temperature
aching joints/body pains

Recovery from infec8on
(exit of microorganism)

Exit of microorganism (to infect other individual)

control the mul2plica2on of the infec2ve agent

Complete destruc2on of the organism and restora2on of a sterile

2ssue

Epidemiology of Infec8ous Disease
Public Health / Community Health
Preven2on
Spread of infec2ous disease in a popula2on of individuals

Involve the whole community
Eradica2on of the source of infec2on
Outbreak preven2on
Factors for Outbreak:
F- number of suscep2ble individuals
I infec2vity of the agent
P popula2on density

Vaccina2on programs
BIOFILMS
Introduc8on
Bacteria that exist as adherent microcolonies (bio2c/abio2c surfaces)

approx 60% of human infec2ons

Chronic, recurrent, device related infec2ons
Formed to maintain and not to be washed away
Provide a more secure environment for sustainability (phagocytosis dicult)

As biolm, bacteria and fungi are less suscep2ble to an2microbials,

they become more tolerant
Biolms in Food industry
Biolms formed on the hard surfaces of food processing plants
Resist many biocides
Ex. Tables, knives, processing equipment
Biolms and medical devices
Medical device-associated infec2on microbial coloniza2on and
biolm forma2on
Indwelling catheters, endotracheal tubes, joint prostheses, surgical

sites
complete removal and replacement of device

Nosocomial infec2ons
Tolerance of biolms to an8microbials
Advent of an2bio2cs
An2bio2c resistant strains of bacteria
Lack of responsiveness to an2microbial therapy
Recurrent UTIs
For an2bio2c to be eec2ve requires 1000x more concentra2on which is
not safe to pa2ents
Adapta2on of biolm - Altered tolerance to drugs
Only in biolm mode and not in planktonic mode

Mechanisms of biolm tolerance

- Compact and highly charged matrix surrounding the biolm
(prevents penetra2on of an2bio2cs)
- Charge of an2bio2c aects penetra2on
Not highly charged an2bio2c easily penetrate the matrix
Highly charged an2bio2c delayed penetra2on

- Channels: nutrients transfer; waste diusions
Persister cells

- Biolms that pre-exist in the popula2on
- Biolms come in several species but may also come in single sp.
- Survive but not grow in the presence of selec2ve agents

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

forma2on
-allows cells to live in close proximity, facilita2ng intercellular
communica2on
Insurance Hypothesis

- Diverse popula2on found in the biolm
- popula2on will survive the stress of an2microbial challenge
- increases toxins in nature
Treatment of Biolm Infec8ons

BeXer use of exis2ng an2microbials
- An2bio2c combina2on (synergies)
- bioFILM PA assay
- Educa2on on an2bio2c fermenta2on

Next genera2on an2microbials

- derived from microbial life form (nature)
- synthesis of an2bio2cs

The End