Mycoplasma/Legionella Flashcards
Primary atypical pneumonia
Acute infectious pulmonary disease caused by:
Mycoplasma pneumoniae (most common) Rickettsia Chlamydia Coxiella burnetii -- Q fever Adenoviruses Parainfluenza virus EBV RSV
Extensive but tenuous pulmonary infiltration and by fever, malaise, myalgia, sore throat, and a cough which at first is nonproductive but becomes productive and paroxysmal
Signs and symptoms of atypical pneumonia
insidious onset, fever, malaise, myalgia, headache, sore throat and cough (usually non-productive). Constitutional symptoms often predominate over respiratory symptoms
Expected sputum analysis of atypical pneumonia
variable amount; gram stain and routine culture often show only mouth flora
Chest xray of atypical pneumo
Pulmonary involvement often greater than expected from mild physical findings. Often see patchy or peribronchial infiltrates, either unilaterally or bilaterally, often with predominantly lower-lobe involvement. Lobar consolidation and pleural effusions are uncommon.
Mycoplasma pneumoniae structure
Size – 125-250 nm; smallest free-living organisms.
Pleomorphic (can be almost any shape) – lack cell wall rigidity and can pass through filters.
Colonies – small, slow-growing. Forms small granular colonies without “fried-egg” appearance after incubation for one week or more (different from most colonies).
No cell walls NO peptidoglycan
Resistant to all cell wall-active antibiotics such as penicillins and cephalosporins, and they do not trigger innate immune responses directed against peptidoglycan, teichoic acid, or lipopolysaccharide.
Stain poorly with Gram stain.
Plasma membranes contain sterols, which must be obtained from the growth medium. Mycoplasmas do not synthesize amino acids, metabolize lipids, or synthesize cholesterol.
Growth and nutrition of mycoplasma
Can grow on complex but cell-free media; require amino acids, fatty acids, and sterols plus appropriate osmotic conditions
Grow slowly in culture (division time >6 hours for M. pneumoniae, colony formation requires 10-21 days).
Associated in nature with humans and other animals (not free-living).
Priamry disease caused by M. pneumoniae
Atypical Pneumonia Tracheobronchitis Wheezing in infants Pharyngitis Rhinitis
How is M. pneumoniae usually transmitted?
respiratory droplets
Attaches to ciliated epithelial cells in the trachea and bronchi of the lower respiratory tract
Specialized structures of M. pneumoniae
Elongated shape when it attaches to surfaces.
Specialized tip structure with a dense core that consists of unique cytoskeletal elements. This unique cytoskeletal structure appears to participate both in binary division and in gliding motility of M. pneumoniae on surfaces.
Attachment factor = protein P1 and a complex of other interacting proteins. Protein P1 exhibits antigenic variation among different isolates of M. pneumoniae. The P1 attachment protein is concentrated on the cell membrane overlying this specialized tip structure, although smaller amounts are present in other parts of the cell membrane.
Cell membrane receptor(s) for attachment of M. pneumoniae: sialoglycoconjugates and sulfated glycolipids have been implicated
What are the mechanisms of host injury of mycoplasma?
Immobilization of cilia of respiratory epithelial cells (ciliostasis) facilitates microbial contamination of lower respiratory tract and interferes with clearance of microbes and secretions.
Produces H202 and other reactive oxygen species that contribute to tissue damage.
M. pneumoniae infection elicits production of many cytokines (including TNF-α, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 and IL-18) that contribute both to clearance of the bacteria and to the disease process.
A novel ADP-ribosylating toxin (CARDS-TX) was reported in 2006 and shown to cause damage to cells in culture that resembles cytopathic effects seen in the respiratory epithelium of infected animals.
Treatment of mycoplasma
oral doxycycline (not in kids)
or
macrolides (e.g., erythromycin, clarithromycin, or azithromycin)
or
fluoroquinolones (levofloxacin, moxifloxacin, or gemifloxacin)
Several regimens of intravenous antibiotics are used to treat hospitialized patients with community-acquired pneumonia.
Resistance to macrolides is emerging in M. pneumoniae
Structure and staining of legionella
Motile, pleomorphic gram-negative rod (stains poorly with gram stain); non-spore forming.
The bacteria are easily stained by fluorescent antibody methods or silver stains, but staining is less sensitive than culture for detecting them
Growth requirements of legionella
Growth occurs over a wide temperature range, requires cysteine and iron, and is fastidious.
Optimal growth in the laboratory occurs on buffered charcoal-yeast extract (BCYE) medium at 35C, and growth is slow (2-6 days to form colonies).
Other characteristics of Legionella (oxidase positive or negative? Catalase positive or negative? Antibiotic susceptibility? What does it produce?)
Oxidase and catalase positive.
Resistant to penicillin because it produces a β-lactamase.
Also produces a hemolysin and a cytotoxin.
Does weird coiling phagocytosis that is distinct but unclear how important it is
Pontiac Fever
Caused by Legionella infection
Acute, self-limited febrile illness (no pneumonia)
Legionnaires’ disease
Symptoms can be extremely variable from mild to severe.
The incubation period is long.
Often the disease presents as pneumonia with fever, malaise, chills, cough (90% of cases), chest pain, headache, diarrhea (30-50% of cases). Extra-pulmonary symptoms are more common that for many other bacterial pneumonias
Route of entry of Legionella
inhalation, aspiration
Spread by inhalation or ingestion of water from aquatic ecosystems or potable water distribution systems contaminated with Legionella.
The role of contaminated non-potable water from cooling systems appears to be less important than indicated by early studies.
Legionnaire’s disease is not transmitted from person-to-person.
How does Legionella avoid host defense mechanisms?
By living within macrophages (a facultative intracellular
pathogen).
Inhibits endosome-lysosome fusion. Endosomes become associated with endoplasmic reticulum to form “ribosome-studded” phagosomes.
Patterns of disease with legionella
can occur in sporadic, endemic, and epidemic forms; higher incidence in late summer, early fall; low attack rate (less than 5%)
Diagnosis of Legionella infection
Demonstration of bacteria in tissue or secretions: Cultures Sputum Silver stain immunofluorescence
Urine antigen test
Serology
Molecular diagnostic tests
Treatment of Legionella infection
Newer macrolides (such as azithromycin or clarithromycin)
quinolones (such as levofloxacin, ciprofloxacin or moxifloxacin)
a ketolide (telithromycin)
tetracyclines (doxycycline, minocycline, tetracycline, tigecycline)
and others (trimethoprim-sulfzmethoxazole, rifampin).
CARDS-TX
“Community Acquired Respiratory Distress Syndrome Toxin (CARDS TX)”
Significant virulence factor for M. pneumoniae
Amino acid sequence homology with the enzymatically active S1 subunit of pertussis toxin
Shares three active-site motifs with several bacterial ADP ribosylating toxins
Purified toxin has ADP ribosylating activity, induces cytopathic effects and vacuolization in mammalian cells, and causes slowing and disorganized ciliary movement plus histopathological changes in baboon tracheal organ cultures
Patients with acute M. pneumoniae infections develop antibodies against CARDS TX
Diagnosis of M. pneumo
Difficult b/c takes a long time to culture and complement fixation and cold aglutinin tests are used more for epidemiology than for practical diagnosing purposes
Can use a combo of PCR and serology for diagnosis
Clinical clues suggestive of Legionnaire’s disease
Diarrhea
High fever (greater than 40 C and 104 F)
Numerous neutrophils but no organisms on Gram stain of sputum
Hyponatremia
Failure to respond to beta-lactam drugs and
aminoglycosides
Water supply contaminated with Legionella
Onset of symptoms within 10 days of hospital discharge
