Pathogenicity Islands and the Type III Secretion

Pathogenicity Islands and the Type III Secretion apparatus - Some bacteria (especially Gram-negative) have genes encoded on their chromosomes or on a plasmid that code for pathogenic characteris - A pathogenicity island is a segment of the bacterial chromosome/plasmid that usually has multiple genes for virulence factors. This sequence is often very different from the rest of the genome; DNA segment containing the genes came from another organism at one time from horizontal transmission - Type III secretion systems are molecular structures that resemble a hypodermic needle located in the cell wall of the bacterium, and are used by the bacteria to inject proteins into a host cell Virus and Pathogenicity - Viruses invade host cells and reside intracellularly - Most pathogenesis caused by virus is due to the induction of inflammation and activation of the immune system (some exceptions) Cytopathic Effects (CPE) - Viruses kill or damage host cell - CPE are characteristic for different types of virus - Formation of giant cells or syncytia are a type of CPE - Infected cells fuse their membranes with other cells, creating a giant cell with many nuclei that functions only as a huge virus producing factory - The giant cell cannot make its own proteins and eventually dies, causing inflammation and later a hole in the tissue - Example: RSV (respiratory syncytial virus), measles virus (rubeola) Viral Pathogenicity 1. Inhibition of macromolecular synthesis in the host cell 2. May cause the host cell to release enzymes, resulting in cell death (apoptosis) 3. May cause a down regulation of MHC I; viral antigens will not be displayed on the cell surface, and the cytotoxic lymphocytes will not recognize that the cell is infected 4. Syncytium formation 5. Deregulation of cell function 6. Induction of chromosomal changes in cells 7. Some can abolish contact inhibition responses by down regulating p53 and rb107, allowing uninhibited cell growth and tumor formation Smallpox is the only disease eradicated because of the application of epidemiology by WHO (1977) - Caused by a DNA virus, the orthopoxvirus, also called variola virus: enveloped, large - Every case of this disease was symptomatic which made it easy to identify (no animal reservoirs) - Vaccination campaigns were successful using a closely related virus; vaccinia - - Disease begins as a respiratory tract infection with inhalation of droplets or contact with viral particles on objects. Virus infects tissues and spreads through the bloodstream to tissues where the lesions erupt. Lesions are always in the same stage of development. Lesions often become secondarily infected with Staphylococcus aureus and other skin bacteria, and sepsis can result, leading to death. Propionibacterium acnes (P. acnes) - Gram-positive, anaerobic, diphtheroid bacillus, which is often a causative organism for acne - Multifactorial blockage in channels transporting sebum to surface - Secondary infection drives the pustular skin disease (could be with S. aureus) Mycobacterial Diseases of the Skin - M. tuberculosis - M. leprae - M. marinum (ulcers following trauma in water) - M. ulcerans (Buruli ulcers) - Must stain with acid-fast stain, aka Ziehl-Neelsen stain - Acid-fast bacilli, aerobic, nonmotile - Production of granulomas or tubercles by the immune system - Extended treatment periods with a cocktail (combination) or antimicrobial agents necessary Hand, Foot, Mouth Disease - Caused by coxsackie virus, an enterovirus, RNA, nonenveloped - Vesicular lesions on skin, buccal mucosa, and tongue - Usually disease of childhood Rubella (German measles) - RNA, Togaviridae, enveloped, one serotype - Milder disease than measles - Macular rash - Complications: rare in children - Adults: encephalitis - Pregnant women: fetal development of congenital rubella syndrome (CRS) Fifth Disease/Parvovirus B19/Erythema Infectiosum/Slapped Cheek Syndrome - Parvovirus, DNA, nonenveloped - Mild rash disease of childhood; usually no complications in children - Pink lacy rash; cheeks become very red, which is usually the first noticeable sign in children - Major complication: TAC (transient aplastic crisis) in pregnant women. Parvovirus has a tropism for nucleated RBCs, and it invades and destroys these cells in the bone marrow. This means that the mother’s hemoglobin can drop 30-40% very quickly, and the fetus will not be getting oxygen. This leads to stillbirth/spontaneous abortion. Acute Sinusitis - Etiology and pathogenesis to otitis media - Clinical symptoms: facial pain and localized tenderness - Complication: abscess formation (often caused by anaerobic bacteria) - Causative organism can be isolated from an aspirate of pus from the sinus Acute Epiglottitis - Most often seen in young children, usually due to H. influenzae type b - Typical sign is that children lean forward to breathe and drool - Bacteria spread from nasopharynx to epiglottis, cause severe inflammation, and the epiglottis will swell shut, closing airways - Life threatening; call for help to intubate Diphtheria - Caused by Corynebacterium diphtheria, an aerobic, Gram-positive, pleomorphic bacillus, non-motile, and non spore-forming - Bacteria do not invade tissues; they produce exotoxin, which diffuses into tissues, inhibits protein synthesis and is neurotropic - Once leading cause of mortality in children - Majority of Canadian cases now found in the far north, droplet transmission - Vaccine-effective (toxoid) - Symptoms: sore throat, fever, malaise, neck swelling, nerve paralysis Diphtheria’s Pathogenicity: - Apathogenic unless the bacterial strain has been “lysogenized” or “transduced,” meaning the organism is infected with a specific bacteriophage with a gene encoding for the toxin - White-gray membrane across back of throat (composed of fibrin, dead tissue cells, leukocytes, and bacterial cells) - Three types of bacterial subspecies: - C. diphtheria gravis - C. diphtheria mitis - C. diphtheria intermedius - All types can be apathogenic of pathogenic - All isolates of C. diphtheriae must be tested for toxin production - Effects of toxins: myocarditis, cardiac failure, polyneuritis - Toxin interferes with protein synthesis in cells, especially nerve cells - Treatment: antibiotics and antitoxin always in combination - Vaccine: effective; must have boosters, tetanus toxoid usually in combination with diphtheria toxoid (DTaP) - Other infections: Cutaneous diphtheria (common in tropics) causes skin ulcers, direct contact transmission Atypical Pneumonia - Includes pneumonia caused by Mycoplasma pneumoniae, Chlamydia psittaci, - Chlamydia pneumoniae, Legionella pneumophila, Coxiella burnetii, and viruses Typically slower onset and tendency to chronicity Often occurs in outbreaks, epidemics, or as zoonoses Pneumonia caused by Mycoplasma pneumoniae - Very small organisms, cannot stain with Gram’s stain (because there is no cell wall) (genetically belong to Gram positive) - Causes “walking pneumonia,” pneumonia that looks terrible on an X-ray, but the person is still walking and behaving relatively normal - Can be responsible for 15%-40% of pneumonia, depending of the year and situation - Often affects school-aged children and teenagers - P1 protein on organism responsible for adhesion (virulence factor) - Can cause neurological complications Symptoms - Low-grade fever; cough, headache - May have erythema (skin manifestations) Diagnosis - Serology, PCR (culture very difficult) Treatment - Tetracyclines, macrolides, no vaccine available Pneumonia caused by Chlamydia psittaci - Very small infectious particle (elementary body) (probably Gram negative but cannot be seen in a normal Gram’s stain because it is too small to be seen in a light microscope) - Obligate intracellular parasite - Zoonosis: birds most common reservoir, especially parrots - Varying severity, from life-threatening pneumonia to a mild pneumonia, depending on the strain Symptoms - Fever, headache, chills, mucus production - Subclinical infectious common Diagnosis - Serology, PCR (culture difficult, need a Class 3 lab (high risk)) Treatment - Tetracycline, macrolide - No vaccine available Pneumonia Caused by Chlamydia (Chlamydophila) pneumoniae - Infectious particle = elementary body (see C. psittaci) - Obligate intracellular organism, can grow in macrophages, smooth muscle cells, endothelial cells, lymphocytes - Droplet transmission - Majority of people have at least one infection with this organism in a lifetime; however, pneumonia does not develop in most - When it causes pneumonia, this is usually a mild disease - Symptoms resemble Mycoplasma pneumoniae, with the addition of fatigue - Subclinical pneumonia and chronic pharyngitis common Laboratory diagnosis - Serology. PCR (culture difficult) Treatment - Tetracyclines, macrolides Pneumonia Caused by Legionella Pneumophila - Gram-negative bacillus, cause of “Legionnaires' disease,” “Pontiac fever” - Can grow in macrophages - Transmitted by inhalation of aerosols; droplet transmission, occurs in outbreaks - Commonly found in water (reservoirs, plumbing of buildings, air-conditioning units) - Relatively resistant to chlorine and temperatures <55% Symptoms - High fever, cough, signs of pneumonia Laboratory diagnosis - Culture, PCR, serology, urine antigen detection Treatment - Macrolides - No vaccine Pneumonia Caused by Coxiella burnetii - Gram-negative, small coccobacillus, obligate intracellular - Zoonosis - Often transmitted by ticks in animals, and human infection is contracted by ingesting contaminated dairy products or inhalation (goats, sheep) Symptoms - Fever (1-2 weeks_, chills, chest pain, headache - Acute and chronic infections occur Laboratory diagnosis - Serology, PCR Treatment - Tetracyclines - No vaccine Other Bacterial Causes of Pneumonia - Usually as secondary infections of in immunocompromised (eg. elderly in nursing homes and auxiliary hospitals) - Gram-positive: S. aureus, S. pyogenes - Gram-negative: Pseudomonas sp., Klebsiella pneumoniae (many gram negatives causing pneumonia in elderly are antibiotic resistant eg. ESBL) Pneumonia Due to CMV (Cytomegalovirus or Human Herpesvirus 5) - DNA virus, Herpesviridae, enveloped - Can cause serious pneumonia Results in nuclear inclusions and large swollen cells (cytomegaly) Chronic infection, lifelong latency after an infection in macrophages and T lymphocytes Virus is shed at intervals in blood, urine, saliva, semen, cervical secretions, and breast milk About 50% of population has antibodies and so have been infected at some time in their lives Transmitted by direct contact, sexual contact, blood, transplanted tissue Cause of ~10% of infectious mononucleosis in healthy individuals (but no heterophile antibodies produced, so the monospot will be negative) Complications: pregnancy, cytomegalic inclusion disease in neonates if mother has the primary infection while pregnant, transplant patients may reject their donated organs, immunosuppressed individuals (eg. HIV) Pneumonia caused by SARS-CoV2 - SARS-CoV2 can cause serious pneumonia especially in elderly and immunocompromised individuals - Studies have shown that even in asymptomatic cases lungs are affected by the virus - This coronavirus attaches to ACE2 enzymes which are the receptors on cells and prevents enzymes from breaking down angiotensin 2 which can be harmful to issues. The inflammation caused by this virus results in a “cytokine” storm and serious consequences. - Pandemic pressure enabled the development of antiviral drugs that are somewhat effective at early stages as well good preventative vaccines - This is an RNA virus that mutates very quickly giving rise to waves of infection - Many studies are ongoing and indications are that ⅕ who are infected with this virus (even if they are asymptomatic) will suffer from Long-Covid Fungal Diseases of the Lower Respiratory Tract Histoplasmosis - Caused by Histoplasma capsulatum, dimorphic fungus (yeast-like morphology in tissues, filamentous mycelium on agar plates - Infection by inhalation of spores from the mycelial form often in bat and bird droppings - Symptoms: similar to tuberculosis (primary lesion in lung) and can also disseminate through the blood and lymph, resulting in lesions in many parts of the body - Initial symptoms mild and subclinical, few cases are severe - Treatment: Amphotericin B or itraconazole Coccidioidomycosis - Caused by Coccidioides immitis, dimorphic fungus - Found in soil in South America and southern US - aka “valley fever” or “San Joaquin fever” - Symptoms: chest pain, fever, coughing, weight loss, tuberculosis-type disease can - develop in about 1% Laboratory diagnosis: isolation of organism from tissue or fluids Treatment: Amphotericin B, ketoconazole, itraconazole Pneumocystis jiroveci Pneumonia - Caused by the yeast Pneumocystis jiroveci, opportunist, normal commensal in many people - Disease of immunocompromised, high mortality due to chronic pneumonia - Incidence increasing as the number of patients increases - Organism found in alveoli in lungs; very difficult to treat in immunocompromised Symptoms - Difficulty breathing, coughing - Often no sputum Laboratory diagnosis: demonstration of the organism in tissue and fluids Treatment: Trimethoprim-sulfamethoxazole Aspergillosis - Genus contains many species of Aspergillus that are ubiquitous in nature - Some species can cause a wide variety of conditions including bronchopulmonary aspergillosis which results from an allergic reaction to the antigen in the lungs - In patients with preexisting lung cavities or chronic lung disorders, Aspergillus can cause infection–fungal ball forms in lung (Aspergilloma) - In immunocompromised patients, disseminated infection is common - Very difficult to treat, sometimes impossible in immunocompromised