Microbial pathogenicity
By
Dr. Carmen Rexach
Microbiology
Mt San Antonio College
Introduction
• Pathogenicity
– ability to cause disease in host
• Virulence
– degree of pathogenicity
• Microbial pathogenesis is tug of war
between virulence and pathogenicity
– When microbe wins, attack of microbe
overpowers host defenses
– When host wins, host defenses control
attack of microbe
To cause disease, most
pathogens:
•
•
•
•
Must gain access into the host
Adhere to the host tissues
Penetrate or evade host defenses
Damage host tissue directly or by
accumulation of microbial waste
products
Portals of entry into host
• Some organisms must enter through
specific portal, others can cause
disease after entry through several
different portals
• Skin
– First line of defense
– Openings in skin, hair follicles, sweat glands
– dermatophytes
Portals of entry into host
• Mucous membrane
– Respiratory tract most
accessible
• Have to overcome cilia,
mucous, macrophage,
IgA, etc.
– GI tract (includes fecaloral route)
• Must overcome pH in
stomach, digestive
enzymes
– Genitourinary tract
Inoculating dose
• Number of organisms needed to cause
disease
• Depends on virulence
– Very virulent, small dose may be sufficient
– Less virulent, larger dose required
• Nonspecific immune response takes out
portion of invaders
Adherence
• Adhesins or ligands
– Molecules on surface of pathogen
– Bind to complementary surface
receptors on cells of host tissues
• Usually glycoproteins, lipoproteins
– Located on glycocalyx or other surface
structure
– Example: fimbriae (pili)
Penetration of host
defenses
• Capsules
– Impair phagocytosis, but not if
opsonized by antibodies
– Produced by nonpathogenic bacteria to
prevent dessication
• Cell wall composition
• Enzymes
Cell wall composition
• M protein of S. pyogenes
– Heat resistant, acid resistant
– On cell surface of fimbriae
– Protective against phagocytosis
• M. tuberculosis
– Wax in acid-fast cells confers
resistance to phagocytosis
– Capable of intracellular replication in
phagocytes
• Common defense mechanism in some
microbes
Intracellular replication
Enzymes
• Exoenzymes = normal products to
allow for absorption of necessary
nutrients, also have harmful effects
– Leukocidins
• Destroys neutrophils and histiocytes
• Produced by Staph/Strep
– Hemolysins
• Causes RBC lysis
α,β,γ hemolysis
Beta-hemolysis
Enzymes
• Coagulases
– Coagulates fibrinogen
– Forms fibrin clot = artificial capsule for
bacteria
– Isolated from host defenses
• Bacterial kinases
– Breaks down fibrin and dissolved clots
– May wall off or isolate pathogen
(streptokinase, staphylokinase)
Streptokinase = thrombolytic
Enzymes
• Hyaluronidases
– Dissolves hyaluronic acid (CT), encouraging
disease spread
• Collagenase
– Breaks down collagen component of CT (muscle,
organs, tissues) to encourage disease spread,
such as gangrene (Clostridia)
Treatment of stem cell cultures with
collagenase frees colonies for removal
Damage to host cells
• Three methods
– Direct damage to cells in close proximity
• Not as common
• May induce phagocytosis by host epithelial cells
• May penetrate by secretion of enzymes
destroying host cells
– Production of toxins transported through
blood and lymph
• Poisonous substances produced by some
microbes
• Results in most associated pathology
• Two types: exotoxins and endotoxins
– Inducing hypersensitivity reaction
Exotoxins
• Proteins produced primarily in grampositive bacteria released into
surrounding medium
• Coded by genes in plasmids or phages
infecting host bacteria
– Some bacteria must be infected by
bacteriophage to produce toxin
• Can be very toxic
Mechanisms & types of
exoenyzmes
• Mechanisms
– Destroys part of host cell or inhibit
metabolic function
• Types
– Cytotoxins
• Kills cells or affects function
– Neurotoxins
• Interferes with nerve impulse transmission
– Enterotoxins
• Affect cells lining GI tract
Protection against
exoenzymes
• Antitoxins = antibodies
• Toxoids = chemically or physically
inactivated toxins which can still
stimulate immune response
– Used as vaccines
Exotoxin producing organisms
• Corynebacterium diphtheriae
– Diphtheria toxin
– Must be infected by lysogenic phage
containing tox gene
– Cytotoxin inhibits protein synthesis in
eukaryotic cells
• Streptococcus pyogenes
– Produces three types of erythrogenic
toxins (cytotoxins)
– Damage surface blood capillaries (red skin
rash, scarlet fever)
Exotoxin producing organisms
• Clostridium botulinum
– Botulinum toxin=neurotoxin produced when
endospores germinate
– Released when cell lyses
– Inhibits release of ACh = flaccid paralysis
• Vibrio cholerae
– Cholera enterotoxin
– Cause epithelial cells lining gi tract to produce large
amounts fluids, electrolytes = interferes with
muscular contraction, severe diarrhea, vomiting
Scarlet fever
Endotoxins
• Part of outer portion of cell wall of gramnegative bacteria
– Lipid A
• Endotoxin (lipopolysaccharide)
• No problem until cell lyses
– Can occur due to exposure to antibiotics =
worsening symptoms
• Defenses
– No effective antibodies produced
Clinical signs and symptoms
• Fever
– Pyrogenic response
– Lipid A induces release of IL-1 from
macrophage
– Carried to hypothalamus, induces prostaglandin
release, increases temperature set point
• Septic shock
– Gram negative bacteria phagocytosed by
macrophage
– Releases TNF with following effects
• Increase capillary permeability resulting in fluid loss,
decrease in blood pressure
• In CSF, causes release of both IL-1 and TNF, increases
permeability of blood brain barrier
Endotoxin producing organsims
• Salmonella typhi
– Typhoid fever
• Proteus spp
– UTI
• Neisseria meningitidis
– Meningococcal
meningitis
Mechanism of action of bacterial toxins
Viruses
• Host defense evasion
– Intracellular reproduction eliminates
exposure to immune system
– Formation of syncytia
• Avoids exposure to ECF and immune system
– Direct invasion of immune effector cells
• HIV invades cells of immune system
• Reproduce in cells, and destroy cells when
virus is released = immunocompromise
CPE:
animal cells invaded by virus
• Three sources of damage
– Accumulation of large #’s of viruses
cause cell death
– Production of viral proteins effect
permeability of plasma membrane
– Inhibition of host DNA, RNA, or protein
synthesis
CPE
Human erythroleukemia cells with virus infection
1. HSV-1
2. CMV
Cytocidal vs. noncytocidal
effects
• Cytocidal
– Disruption of macromolecular synthesis in host cells
• Lysosomes
– Released in cells invaded by cytocidal viruses
• Inclusion bodies
– Negri bodies
• Formation of syncytia
• May cause no changes in infected cell
– Changes in host cell function
• Interferon production
• Host antibody response to viral protein
• Transform host cells
– Loss of contact inhibition
Pathogenicity in Fungi
• No well defined virulence factors
– Capsules
– toxic metabolic byproducts
– allergic response
• Aflatoxin
– Produced by Aspergillus flavus in peanuts
and peanut butter
– Carcinogenic properties
• Poisonous mushrooms
Citreoviridine
• Toxin isolated from Penicillium citreonigrun +
Aspergillus terreus
• Inhibits absorption of Vitamin B1 (thiamine)
– Beri-Beri
– Affects muscles, heart, nervous and digestive systems
– Seen in US only in alcoholics and rarely in gastric bypass
patients
• First report in Dec 2007 from Brazil due to P.
citreonigrun contamination of rice, previously only
in Asia
– 550 cases with 42 deaths
Pathogenicity of
protozoa and helminths
• Protozoa
– Presence of protozoa and waste
products
– Giardia & Trypanosoma able to change
surface coat structure to evade immune
system
• Helminths
– Presence of organisms damages cells and
organs structurally resulting in
symptoms
Pathogenicity of algae
• Neurotoxin produced by few species
• Saxitoxins
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–
–
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Produced by dinoflagellates
Ingested by mollusks
Symptoms of botulism
Red tide