Virulence Factors for Respiratory Pathogens**

Organism

Virulence Factor (VF) or Host Receptor (HR)

Mechanisms

Common cold

Rhinoviruses

ICAM-1 (CD54)(HR)

Allows virus to bind to human cells and then infect the cell

Common cold (COVID-19)

SARS-CoV-2

ACE-2 (HR), Spike protein (VF)

Spike protein binds to ACE-2 on the human cells

Bacterial Rhinosinusitis

Streptococcus pneumoniae

Bacterial capsule (VF)

Prevents WBC phagocytosis

Bacterial Rhinosinusitis

Haemophilus influenzae

Bacterial capsule (VF) or if nontypable—Lipooligosaccharide (LOS) (VF)

Capsule prevents WBC phagocytosis/LOS helps bacterial cells bind to nonciliated epithelial cells

Rhinocerebral mucormycosis

Rhizopus and Rhizomucor

Fungal spores in the air (VF)

Phagocytes of immunocompromised can’t phagocytize the spores fast enough. Spores germinate and hyphae penetrate host tissues and clog blood vessels. Necrosis of host tissues results.

Pharyngitis

Streptococcus pyogenes

Hyaluronic acid capsule (VF) and M protein (VF)

Both prevent WBC phagocytosis

Pharyngitis

Neisseria gonorrhoeae

Pili (VF)

Adherence to columnar epithelial cells and prevents phagocytosis

Pharyngitis (COVID-19)

SARS-CoV-2

Viral spike protein (VF) ACE-2 (HR)

Allows virus to bind to human cells and then infect the cell

Scarlet fever

Streptococcus pyogenes

Streptococcal Pyogenic exotoxin A-C (Spe A-C; erythrogenic toxin A-C) (VF)

Spe A-C can cause damage to the walls of the capillaries in the skin causing the rash seen in scarlet fever.
The Spe toxins are also super antigens that can cause over stimulation of the immune cells and streptococcal toxic shock syndrome

Rheumatic heart disease following pharyngitis

Streptococcus pyogenes

M protein (VF)

Certain M-proteins are antigenic and can cause the host’s B-cells to make antibodies that react with M-protein. These M-protein reactive antibodies also react with some of the human proteins on the surface of the heart valves. These cross-reactive antibodies can with complement cause heart valve damage.

Diphtheria

Corynebacterium diphtheriae

Diphtheria toxin (VF)

ADP ribosylation of host cell elongation factor II stopping host cell protein production and cell death

Epiglottitis

Haemophilus influenzae type b

Bacterial capsule (VF)

Prevents WBC phagocytosis

Bronchiolitis

RSV

CX3CR1 on ciliated human airway epithelial cells (HR)* or heparin sulfate on immortalized tissue culture cells (HR)

Allows virus to bind to human cells and then infect the cell

Influenza

Influenza virus A

Hemagglutinin (VF) and neuraminidase (VF)

Hemagglutinin helps the virus bind to host cells. Neuraminidase helps the intracellular mature Influenza viruses to escape host cells. Change in type of H or N = shift; mutations in H or N = drift

Whooping cough/pertussis

Bordetella pertussis

Filamentous hemagglutinin (VF), cytotoxin (VF), Pertussis toxin (VF)

FH- attachment to ciliated epithelial cells
Cytotoxin- cell death of cells that line trachea
PT- causes nearly ALL the cell damage of the trachea by ADP ribosylating guanine-nucleotide-binding protein (G protein)

Typical Pneumonia

Streptococcus pneumonia, Haemophilus influenzae, and Klebsiella pneumoniae

All produce capsules (VF)

Prevents WBC phagocytosis

Interstitial Pneumonia

Mycoplasma pneumonia

Cytadherence organelle (VF)

Adherence to ciliated columnar epithelial airway cells

Interstitial Pneumonia

Legionella

Binding host C3b to outer membrane porin protein surface (VF)

C3b on bacterial surface binds to host cell complement receptor and the bacterial cells are then endocytosed. Bacteria are facultative intracellular pathogens in alveolar macrophages, monocytes, and alveolar epithelial cells. Bacteria prevent phagosome lysosome fusion and replicate intracellularly.

Interstitial Pneumonia

Viruses

Intracellular pathogens: Invade and multiply in cells of the lungs to avoid elimination (VF)

If they are inside the host it is harder to detect infection until these microbes start producing proteins that are trafficked to the host cell surface. Chlamydia and Chlamydophila prevent phagosome/lysosome fusion after being phagocytized by the alveolar macrophage and other phagocytic cells.

Interstitial Pneumonia (COVID-19)

SARS-CoV-2

ACE-2 (HR); viral spike protein binds to ACE-2

Allows viral spike protein to bind to human cells and then infect the cell

Interstitial Pneumonia

Chlamydia trachomatis, Chlamydophila pneumoniae, and Chlamydophila psittaci

Intracellular pathogens: Invade and live in alveolar macrophages and other cells of the lungs to avoid elimination (VF)

Chlamydia and Chlamydophila prevent phagosome/lysosome fusion after being phagocytized by the alveolar macrophage and other phagocytic cells.
All these bacteria have a unique developmental cycle: they exist in two forms- elementary bodies (EB’s)- metabolically inactive but infectious AND reticulate bodies (RB’s)- metabolically active noninfectious form.

Chronic Pneumonia

Mycobacterium tuberculosis

Can survive in phagocytes even after being phagocytized (VF)

This bacterium survives in the macrophage by preventing phagosome/lysosome fusion and by enzymatically breaking down reactive oxygen species in the macrophage formed by nitric oxide and superoxide anions. Until the macrophages are activated the bacteria can live and multiply in these phagocytes.

Pneumonia in patients with cystic fibrosis

Pseudomonas aeruginosa

Alginate production (VF)

An exopolysaccharide that allows the bacteria to bind to host cells and is part of the matrix surrounding the biofilm that forms in these patient’s lungs. The biofilm protect bacteria from phagocytosis.