Microbial Pathogenesis: Amin - Bakir@hmu - Edu.krd

Microbial
Pathogenesis
Dr. Amin Aziz Bakir
College of Medicine – HMU
amin.bakir@hmu.edu.krd
Microbial Pathogenesis
- Microbial pathogenesis is the ability of microbes, or their
components, to cause infection in a host
- It is a complex mode of interactions between hosts and pathogens
- During the long course of evolution, disease-causing pathogenic

microbes have developed a variety of virulence mechanisms and
virulence encoding factors or genes having inducible or constitutive
expression patterns
The Pathogenicity
The degree of pathogenesis caused by the
interaction of microbe – host and determined by:
1. The virulence factors
2. Intrinsic mechanisms
o The number of microbial entities that are administered
in the host system
o The route of transmission
o Host specific defense mechanisms

Microbial Mechanisms of Pathogenicity
Entry into the Host
The three main portals of entry are:
• Mucous membranes
• Skin
• Parenteral
Mucous Membranes
Epithelial tissue lining the:
- Respiratory tract: Easiest and most frequently used entry
site for microbes
- Gastrointestinal tract: Another common entry site.
- Entry occurs through water, food, contaminated fingers and fomites
- Must survive stomach HCl, enzymes, and bile
- Genitourinary tract: Entry site for most sexually transmitted
diseases (STDs)
- Conjunctiva: Membrane covering eyes and eyelids
The Skin
• Unbroken skin is impenetrable by most

microbes
• Some microbes gain access through hair
follicles and sweat glands.
• Some parasites can penetrate through
intact skin
• Certain fungi (dermatophytes) grow on skin Cutaneous larva (creeping
and produce enzymes that break down eruption) by sandworm
keratin
Parenteral route
Microbes are deposited directly into the tissues beneath the skin
or mucous membranes
- Injections
- Bites
- Cuts & injuries
- Wounds
- Punctures and splitting due to swelling or drying
Preferred Portal of Entry
Many microbes have a preferred
portal of entry which is a prerequisite
to cause disease
Example: Streptococcus pneumoniae

that are inhaled can cause pneumonia
But, if swallowed cause less severe
diseases
Virulence Factors
- Play a crucial role in microbial growth at elevated temperatures
- Promote the adherence, penetration, and dissemination into

their host
- Pathogenic resistance against immune defense:
- Complement system
- Phagocytosis
- Providing evasion from adaptive immune responses
- Nutritional or metabolic factors
- Necrotic factors
- Causing variations in phenotypic morphology

Adherence
Attachment of microbe to host tissue requires:

- Adhesins or Ligands: Surface molecules on pathogen that
bind specifically to host cell surface molecules.
- Can be found on glycocalyx, fimbriae, viral capsid, or
other surface structure.
- Receptors: Surface molecules on host tissues to which
pathogen adhesions bind
Cell Wall Components
M protein: Found on cell surface and fimbriae of Streptococcus

pyogenes. Mediates attachment and helps resist phagocytosis
Waxes: In cell wall of Mycobacterium tuberculosis helps resist

digestion after phagocytosis
Lipopolysaccharide (LPS): causing macrophages to release

interleukin-1 which is carried to hypothalamus (temperature
control center) resulting in fever.
Enzymes
Lyse cells, form or dissolve clots, and dissolve materials in tissue.
- Leukocidins: Destroy white blood cells that are phagocytes
- Hemolysins: Destroy red blood cells
- Coagulases: Produce blots in blood
- Bacterial Kinases: Break down clots produced by body to isolate
infection
- Hyaluronidase: Breaks down hyaluronic acid which holds cells
together in connective tissue
- Collagenase: Breaks down collagen which forms connective tissue of
muscles, skin, and other organs
- Necrotizing Factors: Kill host cells
- Hypothermic factors: Decrease body temperature
- Lecithinase: Destroys plasma membrane of cells
- Proteases: Break down proteins in tissue
Toxin production
- Toxins: Poisonous substances produced by microbes
- Frequently toxins are the main pathogenic factor
- Toxigenicity: Ability of a microbe to produce toxins
- Toxemia: Presence of toxins in the blood
- Toxin effects: May include fever, cardiovascular problems,
diarrhea, shock, destruction of red blood cells and blood vessels,
and nervous system disruptions.
- Of 220 known bacterial toxins, 40% damage euokaryotic cell
membranes
- Two types of toxins:
Exotoxins
Endotoxins
Exotoxins
- Produced mainly by Gram-positive bacteria
- Soluble in body fluids, rapidly transported throughout the body
- Most genes for toxins are carried on plasmids or phages
- Produced inside bacteria and released into host tissue
- Responsible for disease symptoms and/or death:

- Cytotoxins: Kill or damage host cells
- Neurotoxins: Interfere with nerve impulses
- Enterotoxins: Affect lining of gastrointestinal tract
- Toxoids: Toxins that have been altered by heat or chemicals. Can be
used as vaccines for diphtheria and tetanus.
Endotoxin
- Part of outer membrane surrounding Gram-negative bacteria
- Effect exerted when gram-negative cells die and cell walls
undergo lysis, liberating endotoxin
- Causes similar signs and symptoms:
• Chills, fever, weakness, general aches, blood clotting,
tissue death, shock, and even death.
• Can induce miscarriage
• Fever: Pyrogenic response

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Microbial

- During the long course of evolution, disease-causing pathogenic

o Host specific defense mechanisms

• Unbroken skin is impenetrable by most

Example: Streptococcus pneumoniae

- Promote the adherence, penetration, and dissemination into

- Causing variations in phenotypic morphology

Attachment of microbe to host tissue requires:

M protein: Found on cell surface and fimbriae of Streptococcus

Waxes: In cell wall of Mycobacterium tuberculosis helps resist

Lipopolysaccharide (LPS): causing macrophages to release

- Soluble in body fluids, rapidly transported throughout the body

- Most genes for toxins are carried on plasmids or phages

- Produced inside bacteria and released into host tissue

- Responsible for disease symptoms and/or death:

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