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Topics in Microbiology Organ Systems 2007 Respiratory Tract - Upper RT • Bronchioles branch to form the terminal • • • • • bronchioles The terminal bronchioles form the respiratory bronchioles The respiratory bronchioles branch into alveoli It is in the alveoli that gas exchange occurs The surface of the lungs( pleura) and the cavities that they occupy secrete a serous fluid that lubricates Infections are airborne and aerosolized in Respiratory Tree Ears • Exposed to the environment • Pinna - Flaps are somewhat protective • Auditory canal contains hairs and secretes • cerumen a product related to sebum. Ceruminous glands in the ear produce this product Tympanic membrane separates the middle and inner ear( compartmentalizaton) Ear infections • Most middle ear infections arise from the • • microorganisms that move up the Eustachian tube from the nasopharynx Younger children have more infections because of the fact that their auditory tubes are shorter and wider Inner ear infections are rare - If the mastoid area of the cranium becomes infected, causing mastoiditis, there is danger that the infection could reach the brain Respiratory status • Healthy lungs are sterile • Organsims found in the trachea and bronchi are normally transient • Most are removed by the mucocilary escalator( cilia roll bacteria into ball and the microbes are pushed upward, coughing and sneezing can expel the organisms Macrophages • Macrophages are found in the respiratory tree where they engulf both organisms and debris Elusive microbes in the respiratory tree • Mycobacterium tuberculosis are able to remain airborne through the trachea and bronchi • This organism can survive and multiply inside of macrophages • The organism can cause problems by impairing the coughing reflex and can even threaten the alveoli Mycobacterium are Acid Fast • Outer waxy cell wall • • • made from mycolic acid A great proportion of genome is directed at cell wall Slow grower Eludes macrophages Klebsiella pneumoniae • Does not colonize • upper respiratory tract but may be present Passes down the respiratory tract Streptococcal Pharyngitis • About 10% of cases of • • • • • • pharyngitis are caused by Streptococcus pyogenes, Group A Beta Hemolytic strep Some individuals are carriers Inhaled in the form of droplets Adenoids and lymph nodes in the neck swell Pus like lesions are found in the back of the throat High fever Scarlet fever can be caused by the presence of a phage Sinusitis - Inflammation of the sinuses • Staphylococcus • • • aureus H. influenzae Moraxella catarrhalis Streptococcus pneumoniae Bacteroides • Chronic sinusitis may be • • caused by Bacteroides Roots of the upper teeth are very close to the maxillary sinuses Treatment may include application of a warm cloth, drainage, and antibiotic therapy Moraxella catarrhalis • Moraxella • • catarrhalis is a gram negative oxidase positive bacterium Affects people with chronic condition and smokers Leads to bronchopneumoniae Diptheria • Caused by • • Cornybacterium diptheriae Club shaped cells Found in side by side structures called palisades Diptheria • Sequelae are adverse • • • • signs that accompany diptheria Diptheria basically affects the nose and the throat Myocarditis inflammation of the heart Polyneuritis - an inflammation of the nerves Paralysis can occur in rare cases Diptheria • Caused by a • bacteriophage prophage - lysogenic phage Produces an exotoxin Otitis media with effusion • Passage of pharyngeal • • • organisms through the Eustachian tube Fever and earache arise from pressure the pus creates in the middle ear The accumulation of fluid in this area can interfere with hearing Tube can be inserted to prevent middle ear infections The Common Cold • Caused by Rhinoviruses • • • • and Coronaviruses Most infections occur in the spring and fall Rhinoviruses grow best in the epithelium of the upper respiratory tract 113 Rhinoviruses have been identified Natural immunity is rare Corona virus Fomites • Cold viruses spread by contact with touching • • • anything that has come into contact with the infected person If a person blows his nose and then places a Kleenex on the school desk, then the next student who touches the desk, can get the virus on his hands Door handles Shared drink bottles Parainfluenza • Paramyxoviruses • Initially attack the mucous membranes of the • • • • nose and throat Cough and hoarseness after two - three days Barking cough High pitched noise - stridor Two of the four parainfluenza viruses can cause Croup Croup • Acute inflammation of the larynx which can • • • caused an obstruction to the airways High pitched barking sound Respiratory distress By age ten most children have antibodies to all four parainfluenza viruses Whooping Cough • Bordetella pertussis • Incubation period of ten days • Catarrhal phase - fever,sneezing vomiting, and • • • • cough Paroxysmal- mucous and masses of bacteria fill the airway and immobilize the cilia Long strand of mucous in the airway causes violent coughing Cyanosis may result Convalescent Coughing • • • • • Attacks of coughing are severe Can break ribs Vomiting Hemorrhaging can occur Electrolyte imbalance Stages Diagnosis • Charcoal-blood agar medium • Colonies can be fixed • A fluorescent stain be used to identify the organism Mechanisms for Colonization • Adherence mechanisms of B. pertussis involve a "filamentous hemagglutinin" (FHA), which is a fimbrial-like structure on the bacterial surface, and cell-bound pertussis toxin (PTx). Short range effects of soluble toxins play a role as well in invasion during the colonization stage. Pertussis Toxin • One of the toxins of B. pertussis, the pertussis toxin • • (PTx), is also involved in adherence to the tracheal epithelium. Pertussis toxin is a 105 kDa protein composed of six subunits: S1, S2, S3, (2)S4, and S5. The toxin is both secreted into the extracellular fluid and cell bound. Some components of the cell-bound toxin (S2 and S3) function as adhesins, and appear to bind the bacteria to host cells. S2 and S3 utilize different receptors on host cells. S2 binds specifically to a glycolipid called lactosylceramide, which is found primarily on the ciliated epithelial cells. S3 binds to a glycoprotein found mainly on phagocytic cells. Filamentous hemagglutinin • Filamentous hemagglutinin is a large (220 kDa) • • protein that forms filamentous structures on the cell surface. FHA binds to galactose residues on a sulfated glycolipid called sulfatide which is very common on the surface of ciliated cells. Mutations in the FHA structural gene reduce the ability of the organism to colonize, and antibodies against FHA provide protection against infection. However, it is unlikely that FHA is the only adhesin involved in colonization. The structural gene for FHA has been cloned and expressed in E. coli, raising the possibility Additional toxins • Invasive adenylate cylclase • Tracheal Cytotoxin • Lethal toxin Treatment of Whooping Cough • Antitoxin - To combat toxin produced by the bacterium • Erythromycin to shorten the paroxysmal stage Classification of pneumonias • Pleurisy - Inflammation of the pleura - it causes painful breathing • Bronchial pneumonia - Often appears as a secondary infection • Lobar pneumonia - Affects one of the five lobes of the lung Bronchial pneumonia • Can follow exposure to chemicals • Can follow aspiration fo vomitus or other fluids • Infants sometimes aspirate amniotic fluid during birth • Common in the elderly • Transmitted by aerosolized droplets Pneumococcal pneumonia • Sudden infection • Chest pain, cough, and sputum containing blood, mucous, and pus • High fever • Fever may last for five to ten years • Needs to be treated with antibiotics Pneumococcal pneumonia • Fourth leading cause of death in the United States • Chest pain • Cough • Congestion Klebsiella pneumoniae • • • • Multiple serotypes Patient can get reinfected Lesions in the lungs Cephalosporins are effective Klebsiella Pneumoniae Pathogenicity of Klebsiella pneumoniae • Klebsiella pneumoniae and Klebsiella oxytoca are both • • opportunistic pathogens found in the environment and in mammalian mucosal surfaces; They are commonly passed by hands of hospital personnel. Common sites for nosocomial Klebsiella infections inlcude the urinary tract, lower respiratory tract, biliary tract, and surgical wound sites. Clinical syndromes caused by this bacteria include pneumonia, bacteremia, thrombophlebitis, urinary tract infection, cholecystitis, diarrhea, upper respiratory tract infection, wound infection, osteomyelitis, and meningitis Vaccine • The vaccine contains 23 serotypes • Pneumovax • The vaccine is protective against 80% of pneumoccal infections • Revaccination every 10 years is currently recommended Mycoplasma pneumoniae • • • • • Primary atypical pneumonia Mild onset Some people have malaise and fever Patients can be ambulatory - so it is also called “ walking pneumonia” Mycoplasma pneumoniae may cause 20% of all noninfluenza community acquired pneumonias. Mycoplasma • Mycoplasma infections • • are most common in the 5 to 20 age range, Although the disease is usually more dangerous among the middle-aged and elderly. An epidemic occurs every three to five years. Mycoplasma genetics • Interesting organism due to the degeneration of the • • • genome. During their evolutionary history multiple reductions in genome size have occurred, the usual genetic code has been altered, and the overall rate of evolution uncharacteristically high. One suggested reason for the reduction in genome size is the evolution into strict parasites making much of their metabolic machinery obsolete. Mycoplasma also have unique use of the amino acid codon UGA, which they use as an additional codon for tryptophan, while other organisms use it as a stop codon. Mycoplasma as a parasite • Mycoplasma are flask-shaped and are most likely descended from Grampositive bacteria. • Due to their seriously degraded genome they cannot perform many metabolic functions, such as cell wall production or synthesis of purines. • They display the minimal requirements for status as a cell Diagnosis • Isolation of M. pneumoniae from sputum or • • • • • from a nasopharyngeal swab Growth of organisms is slow Serological tests such as immunofluorescence, latex agglutination, and Elisa are of value during this DNA probes are also of use Azithromycin or a fluoroquinolone are drugs of choice. No vaccine is currently available Laboratory Tests Fluorescence Legionnaires • Legionella • • pneumophila Gram negative rod shaped bacteria with an unusual lipopolysaccharide layer 35 serovars are found Legionella pneumophila • • • • • • • Found in soil and water Aerobic Fastidious nutrient requirements Does not ferment sugars Life cycle quite unique Some species can live as intracellular parasites in Amoebas Some of these colonize shower heads and water systems Legionella • Enters the respiratory system as aerosolized droplets • Can be spread by humidifiers and vaporizers in patient rooms • These should be disinfected regularly Pathogenicity • These microbes are taken up by • • • • phagocytes When they are placed in phaglysosomes they thrive in the acidic environment Eventually they break out Lyse the cell Spread Symptoms • • • • • • • Fever Headache Chills Vomiting Fluid in the lungs Can be deadly Nonpneumonic legionella is less severe and is resolved in 5-7 days Psittacosis • Parrot fever • Birds develop this in • • overcrowded situations where the conditions lead to spreading Causative organism is Chlamodophila psittoci Disease is spread by droplets as well as feces Clamydophila psittaci • Infection occurs in the • Previously classified as • • • • • epithelial mucosa Infects macrophages Mild to severe respiratory symptoms result No vaccine is available and there is a 5% mortality associated with infection Antibiotic of choice is Erythromycin • • • Chlamydia Exists as an EB body between infections When the EB body is taken up by phagocytes and placed in lysosomes it is transformed into ad Reticulate Body The Reticulate body begins to reproduce The Reticulate Body is transformed into an EB before being passed to a new host Life Cycle Q Fever – Coxiella burnetiisimilar to Rickettsiae • This organism is a parasite • It can survive long periods of times without a cellular host • It can be transmittted by ticks • It exists as small and large varients • It now appears as though it may form and endospore Pathogenicity of C. burnetii • Bacterium is phagocytized • The bacterium reproduces in lysosomes • The acidic environment actually stimulates their metabolism Transmission • The bacterium may be transmitted by aerosolized droplets • Farmers may be infected by delivering livetock babies • Animal hides may contain organism • Transmitted by contaminated milk Symptoms of Q fever • • • • • • • Chills Fever Headache Penumonia Treated with Erythromycin or fluoquinolones If untreated may result in recurring symptoms A vaccine is available for workers who are continually exposed to livestock or products Nocardia asteroides • Found in soil and water • Transmitted in aerosolized droplets • Immunocompromised patients are vulnerable to this organism • High mortality rates treated with sulfonamides in conjunction with trimethoprim Influenza • Causative agent is an Orthomyxovirus • Influenza virus types A and B are both common causes of acute respiratory illnesses. • Both virus types may cause epidemics of considerable morbidity and mortality but influenza B infections are often limited to localized outbreaks • whereas influenza A viruses are the principal cause of larger epidemics including worldwide pandemics. Viral characteristics • RNA virus • Segmented genome • Recombines to induce • • changes in characteristics Hemagglutinin is resonsigble for infectivity It attaches to a receptor on erythrocytes or host cells Viral characteristics • It takes about 6 hours for the replication of the • • • Orthomyxovirus, killing the host cell in the process. The virus attaches to the permissive cells via the hemagglutinin subunit, which binds to cell membrane glycolipids or glycoproteins containing Nacetylneuraminic acid, the receptor for virus adsorption. The virus is then engulfed by receptor mediated endocytosis It is capable of escaping from the endosome and is released into the cytoplasm of the cell Spread of virus • The RNA enter the nucleus of the cell where • • • fresh copies are made. These return to the cytosol where some serve as mRNA molecules to be translated into the proteins of fresh virus particles. Fresh virus buds off from the plasma membrane of the cell (aided by the neuraminidase) thus spreading the infection to new cells. Antigenic variations • Antigenic drift – results from the mutations that occur in the genes that code for hemagglutinin and neuraminidase • Antigenic shift occurs when two different flu viruses are present in the same cell and then reassortment and recombination can occur ( bird and human) Characteristics • Trasnmitted by respiratory secretion • Inhalation of droplet • Immediate invasion of the oropharyngeal epithelial lining occurs • Damages the cells that line the respiratory pathways.( These are the ciliated mucous producing cells) Severe symptoms • Cellular destruction of the respiratory Epithelium • Impaired phagocytosis • Accumulation of fluid • Fever, malaise,sore throat, and gastroenteritis are common symptoms Treatment of flu • Flu vaccine ( Flu vaccine may prevent heart attacks) • Amantadine – effective against type A influenza ( severe side effects) SARS( sever acute respiratory syndrome) • First described in November, 2002 • Chinese reported numerous cases of an atypial pneumonia • Caused by a corona virus • Causes high fevers, dry cough, and pneumonia Research on SARS • http://www3.niaid.nih.gov/news/newsrel eases/2004/sarsvax.htm • http://www.nih.gov/news/pr/dec2004/n iaid-13.htm • http://www.ncbi.nlm.nih.gov/entrez/que ry.fcgi?cmd=retrieve&db=pubmed&list_ uids=15024391&dopt=medline H5N1 • HPAI A(H5N1) is an avian disease. • There is no evidence of efficient human-to• • human transmission or of airborne transmission of HPAI A(H5N1) to humans. In almost all cases, those infected with H5N1 had extensive physical contact with infected birds. Still, around 60% of humans known to have been infected with the current Asian strain of HPAI A(H5N1) have died from it H5N1 Pandemic Possibility • All influenza viruses have the ability to change • Scientists are concerned that H5N1 virus one day • • could be able to infect humans and spread easily from one person to another. Because these viruses do not commonly infect humans, there is little or no immune protection against them in the human population. If H5N1 virus were to gain the capacity to spread easily from person to person, an influenza pandemic (worldwide outbreak of disease) could beg