Respiratory Tract Bacteria Flashcards
The upper tract (above vocal cords) is colonized by an established and extensive microbial flora. Are there any exception? Describe the flora of the lower respiratory tract.
- middle ear spaces and sinus cavities are sterile
- lower respiratory tract is also sterile
___________ is important in physically removing aspirated particles. Therefore, damage to this process increases one’s risk of lung infection.
-mucociliary flow
When can normal upper respiratory flora become a source of infection?
-when it spreads beyond its niche in the oropharynx and nasopharynx, where it is not associated with symptoms, to normally sterile sites
Acute respiratory infection (ARI) is a leading cause of morbidity and mortality, particularly during what period of life?
-early childhood and in the elderly
What bacterium is the most common cause of community-acquired pneumonia?
-streptococcus pneumoniae (30-50%)
One of the main host defense mechanisms against bacterial infection involves the complement system, which can be bactericidal through what 2 processes?
- generation of membrane attack complex
- opsonization
2 ways successful pathogens circumvent complement
- O-antigen
2. Capsular polysaccharides (CPS)
Describe the O-antigen and what it does
-chains of covalently linked sugar residues extending from the lipopolysaccharaide prevents the membrane attack complex from acting in proximity to the cell membrane
Describe the function of capsular polysaccharides
- limit complement activation and antibody binding
- porous, noncovalently attached zones of polysaccharide that completely envelop and protect the cell
- do not activate complement efficiently in absence of specific antibody and thus serve to protect underlying bacterial cell-surface components
T/F: All CPS are comprised of the same sugar.
False; comprised of different sugar constituents or the same array of sugars linked in different ways
Both O-antigen and CPS tend to be highly immunogenic and are often the dominant antigen on the organism, Because they are the target of selective immune presence in the host, ______________.
-there is often considerable structural and thus antigenic variation
O-antigen and CPS allow extracellular bacterial survival in the non-immune host until ________.
-specific bactericidal and/or opsonic antibody to these polysaccharides is generated and the pathogen is cleared
Why is CPS expression particularly important for an organism to survive for any length in the blood stream?
- that is where complement is most abundant
- why bacteria causing meningitis which requires a sustained bactermia to cross BBB are all encapsulated
Why is a CPS made of sialic acid particularly advantageous?
-it is poorly antigenic, possibly because it is an embryonic “self antigen”
Nickname for Streptococcus pneumoniae
-pneumococcus
Physiology and structure of Streptococcus pneumoniae
- gram positive cocci
- lancet shaped diplococci
- alpha hemolytic on blood agar
- catalase negative, bile salt solube
- optochin sensitive
A discriminating characteristic used to identify the pneumococcus in the lab is its _________.
-susceptibility to optochin
3 diagnostic measures of pneumococcus
- Sputum Gram’s stain
- culture of organism outside its niche in upper respiratory tract (blood, CFS, sputum) but this is problematic for sputum due to contamination as sample passes through the colonized upper airway
- detect of antigen secreted in urine
Discuss the immunity to S. pneumoniae and why it is not always effective
- antibody to CPS is generally protective but requires many days to develop
- due to structural differences among capsules, acquisition of antibody to one type still leaves the host susceptible to other non-cross reactive types
Disease caused by S. pneumoniae is probably more of a function of its ______________________.
-ability to trigger an inflammatory response than the expression of toxins
Polysaccharide capsule allows for evasion of ______________ until….
-complement and antibody until type specific antibody develops
Pneumococcus is a common resident of the _________.
-mucosal surface of human nasopharynx
How is pneumococcus spread?
-person to person spread by colonized individuals through contact with secretions
Pneumococcus is most common in children 65 yrs and may be associated with what 5 predisposing factors?
- eustachian tube dysfunction
- aspiration of nasopharyngeal contents
- antecedent viral (especially influenza!!) disruption of the nasal mucosa
- antibody production is impaired (hypogammaglobinemia, AIDS)
- defective clearance of opsonized bacteria by neutrophils and reticuloendothelial system (splenic dysfunction)
Streptococcus pneumoniae is a prominent cause of ______________.
- lobar pneumonia in which consolidation of the entire lobe has occurred
- lobe infiltrate results from spread within airspaces until tissue barriers are reached
What is the most common pattern for pneumococcal pneumonia?
-lobar infiltrate of entire lobe
Histology of pneumococcal pneumonia
- patchy area of alveoli that are filled with acute inflammatory cells;
- at high magnification, alveolar exudate of mainly neutrophils is seen; surrounding alveolar walls have capillaries that are dilated and filled with RBCs
What does the fact that the alveolar structure is still in tact tell us about pneumococcal pneumonia?
-explains why a pneumonia often resolves with minimal residual destruction or damage to the lung
What does the exudate of penumococcal pneumonia give rise to?
-productive cough of purulent yellow or rust colored sputum
Are there any concerns with antibiotic resistance when treating pneumococcus?
-yes; penicillin and general Beta-lactam antibiotic resistance
Carriage of pneumococcus is especially common in what age period?
-early childhood
Structure and physiology of Haemophilus influenzae
- small
- nonmotile
- gram negative
- pleomorphic coccobacillus
How to identify H. influenzae in the lab?
- culture and its unique growth requirements
- aerobic growth requires 2 supplements: hemin and NAD (factor X and V, respectively)
Next to pneumococcus, _________ is the most common cause of RTI
-H. influenzae
Where is H. influenzae found?
-only resides in the human nasopharynx
Type b vs. non-typeable H. Influenzae
- type b: controlled by immunization with type b CPS
- NTHi: leading cause of acute otitis media and conjunctivitis in children and exacerbations of COPD
What causes otitis media?
- poor drainage through eustachian tube causes the accumulatioon of fluid in the middle ear space. This becomes infected with organisms residing in the upper airway that can transmit up the eustachian tube
- results in painful ear with fever and evidence of inflammation of eardrum
Immunity and Type B H. influenzae
- among capsulated strains, those with type b CPS are the most virulent
- before the vaccination era, it was a cause of life-threatening pneumonia, bacteremia, epiglottitis, and meningitis in young children between 2 months and 4 years of age
- immunity is based on antibody to CPS
Treatment of H. influenzae and resistance
-70-80% sensitive to penicillins; resistance is mediated by expression of beta-lactamase and so many cephalosporins remain effective
Infections due to type b H. influenzae vs. nontypeable strains
- type b: able to cause invasive infection
- nontypeable: unencapsulated and cause infection mostly limited to respiratory tract (pneumonia, acute otitis media)
Neisseria meningitidis structure and physiology
- the meningococcus
- gram negative
- bean-shaped dipplococcus (identical in staining and morph to N. gonorrhoeae)
- at ultrastructural level, it has prominent antiphagocytic polysaccharide capsule
Meningococcal capsular polysaccharides provide the basis for grouping the organism. 12 serogroups have identifies, but which are the most important ones associated with human disease?
-A,B, C, Y, W-135
Where does N. meningitidis colonize and what are its hosts?
- posterior nasopharynx of humans
- humans are the only known host
Carriage rates of meningococcus are highest in what age group and why?
- older children/young adults
- in conditions that promote transmission (dorms, military)
When is the rate of meningococcus transmission the highest?
-late winter and early spring
Which serogroups cause meningococcal meningitis in the US? How about elsewhere?
- US: B, C, Y
- Sub-saharan africa: A, W-135
Name the 2 presentation meningococcemia has.
- skin lesions
2. acute bacterial meningitis
2 types of skin lesions seen with meningococemia infection
- petechiae: minute hemorrhagic spots in the skin
- purpura: larger hemorrhages into the skin
Manifestations of meningococcall meningitis are similar to acute bacterial meningitis causes by S. pneumonia and H. influenze and include…
-fever, altered mental status, headache, nausea, vomiting, and photophobia
T/F: Only meningococcemia with meningitis is considered fulminant sepsis.
- false
- meningococcemia with or without meningitis is characterized as sepsis with rapidly progressive multisystem involvement and high mortality
Immunity of meningococcemia
- high attack rates in infants 6-9 months, the time when maternal antibodies are being lost
- individuals with complement deficiencies may develop it despite protective antibody
How does one diagnose meningococcemia?
-isolation by culture on chocolate agar (hemolyzed blood) from normally sterile sites
Special Neisseria enzymes useful for diagnosis
- contain an oxidative enzyme that turns purple with oxidase reagent
- differentiated from other Neisseria by oxidation of glucose and maltose, but not sucrose or lactose
Drug of choice for meningococcemia and meningococcal meningitis
- penicillin or 3rd generation cephalosporin
- treat people sharing a home with individuals affected: chemoprophylaxis
T/F: Meningococcus does not cause disease where it resides.
-true; colonizes upper respiratory tract but not a major cause of resp. tract disease
In order to prevent infection by encapsulated pathogens, the only effective strategy requires generation of antibody to the CPS. Why is this problematic in the ase of pneumococcus?
- over 90 distinct CPSs with little cross-reactivity
- those at higher risk (young and old) have poor response to immunization; old make antibody but of lower quality and children under 2 do not respond to oligosaccharide antigen
Pneumococcal vaccine
- elicits thymus independent antibody response and so has limitations
- no memory response, lack of affinity maturation and impaired Ig class switching, not immunogenic in children less than 2 years of age
Herd immunity
- became important with conjugate vaccines for H. influenzae, Streptococcus pneumoniae, and neisseria meningitidis
- you are protecting the unvaccinated by vaccinating others
Physiology and structure of Bordetella pertussis
-small, aerobic, gram negative coccobacilli
Where does Bordetella pertussis reside and how does infection spread?
- ciliated surfaces of the upper respiratory tract
- person to person transmission
Pertussis senses environmental signals such as temperature or divalent cations to effect changes in gene regulation through a system called ___________.
-two-component signal transduction systems
List the toxins produced by pertussis
- pertussis toxin
- adenylate cyclase toxin
- tracheal cytotoxin
Function of pertussis toxin
- 5 B subunits for receptor binding while 1 A subunit has ADP-ribosylating functions on G proteins
- similar to cholera toxin
- overproduction of cAMP acts to promote production of respiratory secretion and interfere with neutrophil functions involve in clearance
- mediates binding to epithelial cells and blocks activity of immune effector cells
- toxin marked by lymphocytosis, a hallmark of the disease
What is a hallmark of pertussis disease?
-lymphocytosis due to pertussis toxin
Adenylate cyclase toxin function
-overproduction of cAMP leads to increased secretions in respiratory tract
Tracheal cytotoxin functions
-inhibits ciliary beating which inhibits clearance by the mucociliary elevator
How is Bordetella pertussis spread?
- person to person
- highly contagious and can cause outbreaks
What is the prominent symptom of bordetella pertussis?
-severe cough
3 stages of B. pertussin infection
- catarrhal stage: indistinguishable from viral URI
- paroxysmal stage: episodic coughing, may or may not have inspiratory whoop following paroxysms of coughing
- Convalescent stage: may require weeks; frequent complications in infants who may develop pneumonia or apnea
* * high mortality in infants less than 6 months old**
How to diagnose Bordetella petussis
- diagnose by fluorescent antibody (FA) testing or culture from nsopharyngeal swab
- PCRs should be preferred method
Is B. pertussis identified on routine cultures?
-no, requires non-routine medium such as Bordet-Gengou medium
B. pertussis treatment
- erythromycin or other macrolides, but usually is too late as toxin-mediated damage to respiratory epithelium has already occurred
- treat close contacts
Is there a vaccine for B. pertussis?
- yes
- acellular vaccine DTaP which includes pertussis toxin and other factors
- Tdap booster now recommended to help control outbreaks
- *toxoid vaccine**
What causes walking pneumonia?
-Mycoplasma pneumonia
What is unique about mycoplasma pneumonia?
-extracellular pathogen is lacking a cell wall and therefore is NOT affected by penicillins and beta lactas
Mycoplasma pneumonia causes an “atypical” pneumonia characterized by what?
- insidious onset of fever, headache, malaise and cough
- cough is relatively non-productive of sputum
- multilobe, interstitial infiltrate seen on X ray
Physiology and structure of pseudomonas aeruginosa
- gram negative rod
- non-fermentative, aerobic
- minimal growth requirements allow it to live in many environment
- motile with polar flagella
- some form mucoid colonies on plates
- produces pigments
Epidemiology of Pseudomonas aeruginosa
- ubiquitous, opportunistic pathogen able to infect animals, plants, invertebrates
- common in environment, but not in host flora
- widely distributed in moist, well aerated environments
- intrinsically resistant to many antibiotics
What makes P. aeruginosa eradication difficult?
-it forms biofilms
T/F: P. aeruginosa is often spread by human to human?
-false; this is unusual
What are 3 encapsulated pathogens of the human respiratory tract?
- Streptococcus pneumonia
- Haemophilus influenzae
- Neisseria meningitidis
Will Mycoplasma pneumoniae show on a gram stain?
-no, there is no cell wall
How to identify mycoplasma pneumonia?
- multilobal infiltrate
- not routinely grown in clinical lab
- test by serology or PCR
4 characteristics of places P. aeruginosa thrives
- moisture
- air
- warmth
- damage
5 classes of clinical diseases from Pseudomonas
- pulmonary
- skin infections
- otitis externa
- corneal infections
- bacteremia
Pseudomonas pulmonary infections
- nosocomial pneumonia
- chronic infection in patients with CF
Pseudomonas skin infections
- hot tub folliculitis
- infection of burns
Pseudomonas bacteremia infections
- vascular catheter infections
- neutropenic patients
- due to biofilms
Pseudomonas aeruginosa causes chronic ______ infections in CF patients. What do these strains commonly express?
- mucoid
- alginate- a polysaccharide that blocks effective clearances of this organism
Pseudomonas aeruginosa pathogenesis
- limits neutrophil mediated clearance by contact-dependent injection of toxins
- quorum sensing allows biofilm formation
ExoA toxin
- in P. aeruginoas
- like diptheria toxin, causes inactivation of elongation factor for host protein synthesis
How to diagnose P. aeruginosa
- bacterial culture
- easy to grow in culture, as it has shown it can grow almost anywhere
- ID: oxidase positive, non-lactose fermenting gram negative rod
- pigmentation
- sweet odor
Pseudomonas mechanisms of resistance
- B-lactamases
- mutations in porins reduce uptake
- exchange of plasmids encoding resistance
- reduced susceptibility of biofilms
Treatment of Pseudomonas
- antipseudomonas penicilins
- Ceftriazime
- fluoruoquinolines
- comibination of anti-P penicillin and aminoglycoside
Aside from Pseudomonas, what are 4 other difficult to treat respiratory gram negative rods?
- Burkholderia cepacia
- Stenotrophomonas maltophilia
- Acinetobacter species
- Klebsiella pneumoniae
Why is Klebsiella pneumoniae hard to treat?
-produces an extended spectrum B-lactamase (carbapenemase) enzyme
Legionella pneumophila is an _______ pathogen of humans.
-accidental pathogen
What disease does legionella pneumophila cause?
-Legionnaire’s disease
Structure and physiology of Legionella pneumophila
- gram negative motile (flagella), small coccobacilli
- nutritionally fastidious- does not grow on routine bacteriologic media
- non-fermentative, energy from AA
- poorly stained by gram stain
- INTRACELLULAR PATHOGEN
Why is Legionella pneumophila no stained by gram stain?
-distinct phospholipid content in cell envelop prevents staining
Pathogenesis of L. pneumophila
- parasite of aquatic protozoa
- amoebae are thought to be natural host in environment
- bacteria infect macrophages in humans (thinking they’re amoebas?) and are able to survive, multiply, and spread in intracellular vacuole
- when nutrients become limiting, the bacteria become motile and seek a new protzoan host
Legionella pneumonia’s ability to survive intracellularly in a macrophage is in contrast to what 2 other intracellular pathogens which need to escape for phagolysosome?
- Listeria
- Salmonella
________ genes are required for intracellular growth by Legionella and regulate host phagosome biogenesis and transport to modify the phagolysosome to suit the organism.
-Doc/Icm genes
Where is Legionalla pneumophila commonly found and how it is spread?
- natural bodies of water, water distribution systems (cooling towers)
- outbreaks due to common source of contaminated water
- NO person to person spread; acquisition into respiratory tract by aspiration
Who is at higher risk to getting Legionnaire’s Disease?
- elderly
- those with heavy alcohol/tobacco use
- men vs. women
Clinical disease due to Legionella pneumophila
- common but unreported bc often asymptomatic of flu-like illness referred to as Pontiac fever
- more severe diseases results in pneumonia and extra-pulmonary complications (compromised hosts)
Are defects in humoral or cellular immunity thought to be an issue for legionella?
- cellular immunity
- antibody is not thought to be important for this intracellular pathogen
treatment of Legionella pneumophila
-macrolides or fluoroquinolones that penetrate into host cells
How to diagnose legionella?
-urine antigen test useful as it is not routinely cultured
Legionella is an ______ pathogen obtained from ________.
- intracellular
- aerosolized contaminated water sources
