Bacterial Pathogenesis

OR
Bacterial Mechanisms of Pathogenicity
 Bacterial Pathogenesis
OR
Bacterial Mechanisms of Pathogenicity

 Pathogenesis
 The word comes from the Greek pathos, "disease", and genesis, creation.
 The term pathogenesis means step by step development of a disease.

 The chain of events leading to that disease due to a series of changes in the
structure and /or function of a cell/tissue/organ.
 Caused by a microbial, chemical or physical agent
 Terminologies

 Disease
• Any deviation from a condition of good health and well-being

 Infectious Disease
• A disease condition caused by the presence or growth of infectious
microorganisms or parasites

 Pathogenicity
• The ability of a microbe to cause disease

 Virulence
• The degree of pathogenicity in a microorganism
 Terminologies

Acute Infection An infection characterized by sudden onset, rapid progression,

and often with severe symptoms

Chronic Infection An infection characterized by delayed onset and slow

progression

Primary Infection An infection that develops in an otherwise healthy individual

Secondary Infection An infection that develops in an individual who is already

infected with a different pathogen
 Terminologies

 Localized Infection An infection that is restricted to a specific location or

region within the body of the host

 Systemic Infection An infection that has spread to several regions or

areas in the body of the host

 Clinical Infection An infection with obvious observable or detectable

symptoms

 Subclinical Infection An infection with few or no obvious symptoms

 Terminologies
 Opportunistic infection An infection caused by microorganisms that are
commonly found in the host’s environment. This term is often used to refer to
infections caused by organisms in the normal flora.

 Epidemiology The study of the transmission of disease

 Communicable Disease A disease that can be transmitted from one individual

to another

 Non communicable Disease A disease that is not transmitted from one

individual to another.
 Terminologies
 The suffix “-emia”
o A suffix emia meaning “presence of an infectious agent”
o Bacteremia = Presence of infectious bacteria
o Septicemia = Presence of an infectious agent in the bloodstream

 The suffix “-itis”

o A suffix itis meaning “inflammation of” Examples:
o Pharyngitis = Inflammation of the pharynx
o Endocarditis = Inflammation of the heart chambers
o Gastroenteritis = Inflammation of the gastointestinal tract
 Terminologies

• Endemic Disease
– An endemic disease is a disease that is always present in a certain
population or region.

– Malaria is a constant worry in parts of Africa .

 Terminologies

• Epidemic Disease
– Epidemic: An outbreak of disease that attacks many peoples at about the
same time and may spread through one or several communities. e.g.
dengue in KPK

• Pandemic Disease
– When an epidemic spreads throughout the world.

– An epidemic affecting a large geographical area; often on a global scale e.g.

HIV
 Terminologies

 Reservoir of Infection
– The source of an infectious agent

 Carrier
– An individual who carries an infectious agent without manifesting
symptoms, yet who can transmit the agent to another individual

 Fomites
• Any inanimate object capable of being an intermediate in the indirect
transmission of an infectious agent, such as clothes, utensils, and furniture.
 Terminologies

 Animal Vectors
– An animal (nonhuman) that can transmit an infectious agent to humans

– Two types: mechanical and biological

– Mechanical animal vectors: The infectious agent is physically transmitted

by the animal vector, but the agent does not incubate or grow in the
animal; e.g, the transmission of bacteria sticking to the feet of flies

– Biological animal vectors: The infectious agent must incubate in the animal
host as part of the agent’s developmental cycle; e.g, the transmission of
malaria by infected mosquitoes
 Mechanisms of Disease Transmission

• Direct Mechanisms of Disease Transmission

– Directly From Person to Person

– Examples:
Direct Skin Contact
Airborne (Aerosols)

• Indirect Mechanisms of Disease Transmission

– Examples:
Food & Waterborne Transmission
Fomites
Animal Vectors
Bacterial Mechanisms of Pathogenicity:
How Microorganisms Cause Disease
 Portals of Entry

• 1. Mucus Membranes

• 2. Skin

• 3. Parentarel
 1. Mucus Membranes

• A. Respiratory Tract
– microbes inhaled into mouth or nose in droplets of moisture or dust
particles
– Easiest and most frequently traveled portal of entry
 1. Mucus Membranes

• B. Gastrointestinal Tract
– microbes gain entrance thru
contaminated food & water or fingers
& hands

– most microbes that enter the G.I. Tract

are destroyed by HCL & enzymes of
stomach or bile & enzymes of small
intestine
 Fecal - Oral Diseases

• These pathogens enter the G.I. Tract at one end and exit at
the other end.

• Spread by contaminated hands & fingers or contaminated

food & water
• Poor personal hygiene.
 Mucus Membranes
• D. Conjunctiva –
– mucus membranes that cover
the eyeball and lines the eyelid

• Trachoma
– Chlamydia trachomatis
 2nd Portal of Entry: Skin

• Skin - the largest organ of the body. When unbroken is an effective

barrier for most microorganisms.

• Some microbes can gain entrance through openings in the skin: hair
follicles and sweat glands, wound …etc
 3rd Portal of Entry: Parentarel

• Microorganisms are deposited into the tissues below the skin or mucus
membranes
• Punctures and scratches

• injections

• bites

• surgery
 Preferred Portal of Entry

• Just because a pathogen enters your body it does not mean it’s going to cause
disease.
• Pathogens - preferred portal of entry
• Streptococcus pneumoniae
– if inhaled can cause pneumonia
– if enters the G.I. Tract, no disease
• Salmonella typhi
– if enters the G.I. Tract can cause Typhoid Fever
– if on skin, no disease
 Number of Invading Microbes

• LD50 - Lethal Dose of a microbes toxin that will kill 50% of

experimentally inoculated test animal

• ID50 - infectious dose required to cause disease in 50% of inoculated

test animals

– Example: ID50 for Vibrio cholerea 108 cells (100,000,000

cells)

– ID50 for Inhalation Anthrax - 5,000 to 10,000 spores ????

 How do Bacterial Pathogens Penetrate
Host Defenses?
Adherence - almost all pathogens
have a means to attach to host tissue

Binding Sites
• Adhesins

• Ligands
 Some cells use fimbriae to adhere.

• Fimbriae can play a

role in tissue
tropism. Example -
attachment of Candida
to vaginal epithelial cells
• Bacteria typically employ proteins known as Adhesins to attach to host
tissues, which usually are located on ends of fimbriae.
 2. Capsules
• Prevent phagocytosis
K. pneumoniae
• Attachment

• Streptococcus pneumoniae

• Klebsiella pneumoniae

• Haemophilus influenzae

• Bacillus anthracis

• Streptococcus mutans
Avoidance of Phagocytosis

Capsules are Involved in

avoidance of phagocyte-mediated
recognition and attachment.
 3. Enzymes
• Many pathogens secrete enzymes that
contribute to their pathogenicity
 Summary of How Bacterial Pathogens
Penetrate Host Defenses
• 1. Adherence
• 2. Capsule
• 3. Enzymes
– A. leukocidins B. Hemolysins
– C. Coagulase D. Kinases
– E. Hyaluronidase F. Collagenase
– G. Necrotizing Factor H. Lecithinase
 4. Toxins
• Poisonous substances produced by microorganisms

• Toxins - primary factor - pathogenicity

• 220 known bacterial toxins

– 40% cause disease by damaging the Eukaryotic cell membrane

• Toxemia
– Toxins in the bloodstream

• Toxigenicity:
– Capacity of microorganisms to produce toxins.
 Two Types of Toxins
• 1. Exotoxins
– Secreted outside the bacterial cell

• 2. Endotoxins
– Part of the outer cell wall of Gram (-) bacteria.
 Exotoxins
 are protein toxins, generally quite toxic and secreted by bacterial cells
(some Gram +ve, some Gram -ve)
 can be modified by chemicals or heat to produce a toxoid that still is
immunogenic, but no longer toxic so can be used as a vaccine .
 A-B (or "two") component protein toxins
o B component binds to specific cell receptors to facilitate the
internalization of A.
o A component is the active (toxic) component

• Exotoxins may be subclassed as enterotoxins, neurotoxins, or cytotoxins.

 Endotoxins (Lipopolysaccharide LPS)
 Part of outer membrane surrounding gram-negative bacteria.

 Endotoxin is lipid portion of lipopolysaccharides (LPS), called lipid A.

 Effect exerted when gram-negative cells die and cell walls undergo lysis,
liberating endotoxin.
 All produce the same signs and symptoms:

• Chills, fever, weakness, general aches, blood clotting and tissue

death, shock, and even death.
• Fever: Pyrogenic response is caused by endotoxins.
Exotoxins versus Endotoxins
 Three Types of Exotoxins
• 1. Cytotoxins
– kill cells e.g. Diphtheria toxin

• 2. Neurotoxins
– interfere with normal nerve impulses.e.g. Botulinum Toxin

• 3. Enterotoxins

– effect cells lining the G.I. Tract. e.g. Cholera toxin or choleragen.
Bacterial Mechanisms of Pathogenicity: How
Microorganisms Cause Disease