Chapter 15:Microbial Mechanisms of

Pathogenicity

Microbial Mechanisms of Pathogenicity

• Pathogenicity: The ability to cause disease

Portal of entry: route for pathogens to gain entry into host

─ Mucous membranes

◦ GI tract, respiratory tract, genitourinary tract

─ Skin (Intact)

◦ Hair follicles, sweat gland ducts

─ Parenteral route

◦ Microbe deposition when barriers are penetrated (punctures, wounds, bites)

• Some microbes have preferred portals of entry

Factors influencing microbial pathogenicity:

Portals of Entry

Factors influencing microbial pathogenicity:

Portals of entry

*Easiest to acquire

• The likelihood of disease development increases as the number of invading microbes increases

• ID50: Dose required to infect 50% of the test population

• LD50: Lethal dose (of a toxin) for 50% of the test population

Factors influencing microbial pathogenicity:

Numbers of Invading Microbes

Portal of entry ID50

Skin (Parenteral route) 10-50 endospores

Inhalation 10,000-20,000 endospores

Ingestion 250,000-1,000,000 endospores

Toxin LD50

Botulinum toxin 0.03 ng/kg

Shiga toxin 250 ng/kg

Staphylococcal enterotoxin 1350 ng/kg

Bacillus anthracis:

*Most potent toxin

• Direct interactions between microbial adhesin proteins and host cell receptor proteins

─ Adhesins: components of microbial extracellular structures (capsule/glycocalyx, fimbriae, flagella)

Factors influencing microbial pathogenicity:

Adherence/Attachment

Figure 15.1

Factors influencing microbial pathogenicity:

Adherence/Attachment• Biofilms are another type of substrate for attachment for some microbes

─ Indirect interactions between microbe and host

─ Bacteria adhere to host cell surface and secrete sticky glycocalyx, to which more microbes can attach

◦ Concentrate nutrients, provide protection for bacteria

◦ Dental plaques

─ Biofilms are estimated to be involved in at least 65% of all bacterial infections in humans

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Biofilm on a catheter

Microbial Mechanisms for Penetrating Host Defenses

• Impairment of phagocytosis (by host cells)

─ Cell wall components (i.e. mycolic acid)

─ Capsules

http://www.stemworks.org/anthrax/anthraxmicrographs.html

B. anthracis with capsules surrounding a macrophage

Microbial Mechanisms for Penetrating Host Defenses

• Impairment of phagocytosis

• Disguises

─ Antigenic variation: altering surface antigens so host antibody responses will be unsuccessful

◦Where have we seen this before?

• Penetration into host cell

─ Some bacteria can move and multiply within host cells

◦Host cells can be microbial hideouts Trypanosoma brucei

Figure 22.5

Bacterial Mechanisms of Host Cell Damage

• Using host cell’s nutrients

─ Siderophores: secreted bacterial proteins that collect host’s irondepletion of host iron stores

• Direct damage to host cells

─ Plasma membrane damage from bacterial penetration

─ Bacterial waste products

─ Host cell rupture (excessive bacterial multiplication)

• Toxin production

Bacterial mechanisms of host cell damage:

Toxins

• Toxins: poisons produced by some microorganisms

• Two types of toxins:

─ Exotoxins (proteins secreted by bacteria)

─ Endotoxins (within bacterial cell walls)

Bacterial mechanisms of host cell damage:

Exotoxins

Figure 15.4a

• Protein products of bacterial cells

─ Secreted from bacterial cell

◦ Gram-positive or Gram-negative cells

─ Proteins (sometimes enzymes)

◦ Typically low LD50

─ Three types:

◦ Membrane-disrupting toxins

◦ Superantigens

◦ A-B toxins

• Membrane-disrupting toxins

─ Lyse host’s cells by:

◦ Making protein channels in the plasma membrane

◦ Disrupting phospholipid bilayer

◦ Exotoxin from C. difficile

Bacterial mechanisms of host cell damage:Exotoxins: Membrane-disrupting

toxins

• Superantigens

─ Overstimulation of the host immune response

◦ Cause an intense immune response due to release of cytokines from host cells

─ Fever, nausea, vomiting, diarrhea, shock, death

─ Toxic shock syndrome (TSS): toxin produced by a strain of S. aureus

Bacterial mechanisms of host cell damage:

Exotoxins: Superantigens

• A-B toxins

─ Cholera toxin

Figure 15.5

Bacterial mechanisms of host cell damage:

Exotoxins: A-B toxins

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• Clostridium botulinum

─ Endospore-forming, obligate anaerobe

─ Found in soil, freshwater sediments

• Intoxication due to ingestion of botulinum toxin

─ A-B neurotoxin

◦ Most potent natural toxin

─ Ingestion of endospores by adults usually not harmful

• Botulinum toxin blocks release of a neurotransmitter at the neuromuscular junction

─ Loss of muscle movement (flaccid paralysis)

─ Death due to respiratory and cardiac failure

Bacterial exotoxins:

Botulism

• Treatment: supportive care and antitoxin

─ Slow recovery; nerve endings must regenerate

• Infant botulism results from C. botulinum growing in intestines

─ Endospores germinate in digestive tract

─ Infants don’t have sufficient normal microbiota to outcompete C. botulinum

• Prevention:

─ Proper canning

─ Infants less than one year old should not ingest honey

Bacterial exotoxins:

Botulism

Bacterial mechanisms of host cell damage:

Endotoxin

• Lipid component of lipopolysaccharide portion of outer membrane of gram-negative bacteria

• Released during bacterial cell death and multiplication

Figure 15.4b

Bacterial mechanisms of host cell damage:

Endotoxin

• Endotoxin release

─ Fever

─ Blood clots

─ Septic shock

Sepsis and Septic Shock• Normally, no bacteria in our blood

─ But, if they overcome our defenses and gain access to our blood, they may undergo uncontrolled proliferation

• Sepsis: infection of the blood with pathogens

─ Bacteremia: presence and proliferation of bacteria in blood

• Shock: life-threatening decrease in blood pressure

• Septic shock: shock caused by sepsis (50% mortality)

─ Low blood pressure is uncontrollable

─ Dysfunction of at least one organ

• Gram-negative Septic Shock

─ Endotoxins trigger blood pressure decrease

◦ Decreased blood flowimbalance between oxygen delivery and consumption

─ Initial symptoms are nonspecific and do not cause alarm

◦ Antibiotics may arrest the progression, but are rarely given at such an early stage

─ Progression to lethal stages is rapid, nearly impossible to treat

◦ Antibiotics at later stages can worsen condition by killing bacteria

◦ Eventually leads to multiple organ failure

Sepsis:Gram-negative Sepsis

Sepsis:Gram-positive Sepsis• Often due to invasive hospital procedures that

allow Gram-positive pathogens to enter the bloodstream (i.e. nosocomial)

─ Staphylococcus aureus

◦ Staphylococcal toxin causes toxic shock syndrome

−Superantigen exotoxin: causes release of fluids from capillarieslower blood pressure, shock

─ Streptococcus pyogenes

◦ Common cause of puerperal sepsis (childbirth fever)

◦ Transmitted to birthing mother by physicians/ midwives

−Superantigen exotoxin: damage to blood capillaries

−Uterine infectionperitonitissepsis

• Generally same portal used for entry

• Respiratory tract

─ Coughing, sneezing

• Gastrointestinal tract

─ Feces, saliva

• Genitourinary tract

─ Urine, vaginal secretions

• Skin (wounds)

• Blood

─ Biting arthropods, needles/syringes

Portals of Exit