Microbial pathogenicityMicrobial Microbial pathogenicitypathogenicity

ByByDr. Carmen RexachDr. Carmen Rexach

MicrobiologyMicrobiologyMt San Antonio CollegeMt 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 fecal-oral 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 lysisα,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 gram-

positive 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 erythrogenictoxins (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 gram-

negative 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 infection1. HSV-1 2. CMV

Cytocidal vs. noncytocidaleffects

• 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

– Produced by dinoflagellates– Ingested by mollusks– Symptoms of botulism– Red tide