Exoenzymes and Toxins & Respiratory Infections

Respiratory System

• Upper Respiratory Tract (URT)

• Lower Respiratory Tract (LRT)

Upper Respiratory Tract (URT)

• paranasal sinuses

• nasopharynx

• oropharynx

• epiglottis

• larynx

• lined with normal bacterial flora or indigenous microbiota

normal bacterial flora or indigenous microbiota

• protect body from potential pathogens

In a normal person in the community, what normal flora are found in their URT?

• staphylococcus sp.

• streptococcus sp. 

  • streptococcus pneumoniae

  • viridans streptococcus

• haemophilus sp.

• anaerobes

In a normal person in the hospital or LTC, what normal flora are found in their URT?

• staphylococcus spp.

• anaerobes

• Enterobacteriaceae

  • e. coli

  • klebsiella spp.

• candida spp.

• pseudomonas spp.

Lower Respiratory Tract (LRT)

• trachea

• bronchial tubes

• alveoli of the lungs

• sterile, no microbiota/normal flora

Opportunistic infections

may be caused by indigenous microbiota of the URT of the respiratory system

Normal Flora of Nares (nostrils)

• staphylococcus epidermis

• corynebacteria

• staphylococcus pneumoniae

• Neisseria sp.

• haemophilus sp.

• streptococcus pneumoniae

Normal Flora of Nasopharynx (URT)

• non-hemolytic streptococci

• alpha-hemolytic streptococci

• Neisseria sp.

• streptococcus pneumoniae

• streptococcus pyogenes

• haemophilus influenzae

• Neisseria meningitidis

LRT Infections

• most common cause of death from infectious diseases in US and globally

• most common and most deadly communicable diseases (pneumonia and influenza)

  • numbers dropping since 1980 for 5-14 and 5-24 age groups

• rise in non-communicable diseases like COPD

  • more chronic diseases

  • longer lifespans = living longer = more likely to develop chronic disease and die from it

COVID and Influenza

• type of infection

• deaths

• compared to total infectious disease deaths

• LRT infections

• Covid-19

  • 7 million deaths from 704,500,000 cases

• Flu/Pneumonia:

  • 11 million deaths

• more than 34 million deaths from infectious diseases overall

Syndromes associated with URT

• sinusitis

• rhinitis

• otitis media (middle ear)

• tonsilitis

• pharyngitis

• epiglottitis

Syndromes associated with LRT

• bronchitis

• bronchiolitis

• pneumonia

Epiglottitis

• inflammation of epiglottis (flap of skin covering larynx)

• swelling → respiratory blockage

• we see this complication in children with swollen epiglottis → obstruction of airway and breathing

• frequent bacterial causes:

  • haemophilus influenzae

  • streptococcus pyogenes

Tonsilitis

infection of tonsils

Sinusitis

inflammation of sinuses → filling with fluid and infection

Acute rhinitis

• commonly seen with common cold

• swelling and inflammation of nasal mucus membranes

Laryngitis

inflammation of mucus membranes of voice box (larynx)

pharyngitis

• infection of pharynx → sore throat, potentially strep throat

  • streptococcus pyogenes causes bacterial pharyngitis

  • sore throat (not strep): viral

  • most cases are caused by viruses and not s. pyogenes

• streptococcal pharyngitis

streptococcal pharyngitis

• reservoirs: infected humans

• transmission: person to person, direct contact (hands, droplets/secretions, carriers)

• hospitalized patient care

  • standard precautions

  • droplet precautions for infants/young children

viruses that infect the URT

• rhinovirus - most common

• coronavirus - not just covid/SARS

• influenza virus

• parainfluenza virus 

• respiratory syncytial virus

• herpesvirus

• adenovirus

• bocavirus

• coxsackievirus

• enterovirus

• RSV

RSV

• high-risk populations:

  • premature babies in first year of life

  • infants under 6 months

  • children with asthma

  • patients of an age with a weakened immune system or underlying lung or heart problems

  • older people

• leading cause of infant hospitalization in the US

• almost all children under 2 will get RSV

• common respiratory virus that causes mild, cold-like symptoms

• immunizations can protect infants, some young children, and at-risk or older adults

Current RSV, flu, and Covid rates

• RSV and flu hospitalization rates are low

• Covid hospitalization peaking (sept./oct.) and then we will likely see another peak (jan./feb.)

  • right now, ~3 hospitalizations per 100,000 people

  • morbidity/incidence rate (number of people with new infection of covid/flu/RSV)

• 2025: <1% of deaths were associated with Covid

• correlation between hospitalization and deaths caused by these diseases

viruses that infect the LRT

• influenza virus

• parainfluenza virus

• respiratory syncytial virus

• adenovirus

• bocavirus

• metapneumovirus

Flu Viruses

• Type A

• Type B

• 47-82 million flu illnesses last flu season (last fall - last april)

  • increased numbers last year

• virulence factors present

  • H Spike

  • N Spike

Flu H Spike

• Hemagglutinin Protein (HA) is an adhesin that recognizes and attaches to receptors, or integrins, present on respiratory cells

• for the H spike, Hemagglutinin helps virion attach and penetrate host cells

Flu N Spike

• Neuraminidase (NA) helps release virions from the host cell after replication and assembly

Why do we need a new flu vaccine every year?

H and N spikes are constantly changing and mutating

Flu virus infecting cell process

Major mechanisms (most important virulence factors) by which pathogens cause disease

• exoenzymes or toxins the pathogens produce

• some pathogens produce both

Exoenzymes

• enzymes that act outside the cell that produces them

• examples of exoenzymes released by bacteria:

  • necrotizing enzymes: cause destruction of cells and tissues

    • necrotizing fascilitis

  • coagulase: causes clot formation around cells, protecting bacteria from phagocytosis and other cell defenses

  • kinase: bacteria later produce to dissolve clot and release bacteria

    • streptokinase (SK): bacterial protein produced by B-hemolytic streptococci 

      • Acts indirectly by forming plasminogen-streptokinase complex (activator complex) which converts inactive plasminogen into active plasmin 

      • SK is non-fibrin specific 

      • Can degrade fibrin clots as well as fibrinogen and other plasma proteins 

  • hyaluronidase

  • collagenase

  • hemolysins

  • lecithinase

Toxins

• poisonous substances released by various pathogens to damage host tissues and cause disease 

• endotoxins

• exotoxins

Endotoxins

• part of cell wall structure of gram-negative bacteria 

• Released from cell walls of bacteria 

• can cause serious, adverse physiologic effects such as fever and shock 

  • Toxin = pyrogenic (causes fever) 

• Liberated when bacteria die and cell wall breaks apart 

• Lipopolysaccharides act throughout the body 

• Fever, weakness, aching, septic shock 

• Typhoid fever and meningitis

• gram-negative

Exotoxins

• Produced within cell, then released 

• Examples: neurotoxins, enterotoxins (GI), exfoliative toxin, erythrogenic toxin (causes redness), leukocidins (destroy WBCs) 

• gram-positive

• act at specific sites

• produce characteristic diseases

• Diphtheria, Tetanus

Neurotoxins

• most potent exotoxins

• Clostridium tetani: spastic, rigid muscle contraction

Enterotoxins

• exotoxins

• C. diff

• causes Pseudomembranous Colitis (PMC)

Erythrogenic Toxin

• exotoxin

• Scarlet Fever

• caused by strep pyogenes

Staph. Aureus TSST-1

• exotoxin

• Toxic Shock Syndrome

Exfoliative Toxin

• exotoxin

• scalded skin syndrome

• produced by S. aureus

gram-positive vs. gram-negative

• impacted by peptidoglycans

• crystal violet penetrates cell and stains peptidoglycan layer(s), decolorizer is added to stained cells

• stain remains purple on gram-positive (thick peptidoglycan layer): exotoxins

• stain becomes pink on gram-negative (thin peptidoglycan layer): endotoxins

Virulence Factors Diagram