22 - Bacterial Pathogens of the Respiratory Tract Flashcards
How do we divide the respiratory tract clinically and what is a key difference between the two?
Upper and lower!
upper-non-sterile
lower-sterile
WHat are 5 ways that bacteria and enter/spread into the lower (sterile) respiratory tract
- direct inhalation: determined by particle size
- aspiration of upper airway contents
- spread among mucous memebrane surface
- hematogenous spread
- direct penetration (ie intratracheal tube)
What are 5 important defense barriers to bacterial infections?
- Ability to filter particles based on size (air flow and vibrissae)
- mechanical restriction (epiglottis and cough refelx)
- Mucociliary escalator (propels material away form the lulngs)
- Respiratory tract secretions (antimicrobial peptides, lactoferrin/transferrin, sIgA antibodies, lysozyme, etc)
- Localized immune cells and other host factors (phagocytes, immunoglobins, complement)
What are 6 general strategies used by bacterial pathogens of the RT to overcome/subvert host barriers?
- Adherence and/or invasion to/of RT tissues (pili, fimbriae, adhesions)
- secretion of tissue damaging enzymes (lysins, proteases, elastases)
- factors that inhibit or neutralize host defense mechanisms (proteases, capsule)
- Toxins that alter/inactivate host cell functions ribosylte G-proteins and EF-2, phopholipases
- factors that overstiumlate the immune response superantigens, etc
- from microcommuniites (biofilms) to resist elimination overproduce plysaccarides (alignate)
What are the 2 possible morphologies of organisms that are gram-positve? Please give one example per morphology.
coccus: staphylococcus clusters, streptococcus chains
rod(bacillus): corynebacterium
What is an example of an organism that is acid-fast and what is its morphology?
Mycobacterium
What are the 2 possible morphologies of organisms that are gram-negative? Please provide some examples.
Coccus: Neisseria
Rod: Pseudomonas, legionella, Haemophilus
Coccobacillus: bordetella
What is the morpholgy of an organism that has no cell wall? Please give an example.
Pleomorphic: Mycoplasma
(note this is not mycobacterium. mycobacterium is acid fast rod)
What are the important features of Bordetella pertussis?
morphology/gram stain
aerobe vs anerobe
virulence mechanisms
population of infection
- gram negative coccobacillus
- strict aerobe
- produced pertussis toxin (PTx)
- adheres to cilia of respiratory epithelium and expresses several adhesins including FHA (filamentous hemagglutinin), pertactin, pili
- bacterium is highly infectious and transmittable
- primary disease of the young, but adults may be asymptomatic carriers
What disease is associated with Bordetella pertussis? What are its 3 distinct phases? Is there a vaccine?
Whooping cough (pertusssis)
3 distinct phases: catarrhal, paroxysmal, convalescence
Vaccine available (acellular against PTx, FHA, pertactin) but possibly is waning in efficacy
what is the mechanism of disease elicitation for B. pertussis?
Results in whooping cough!
- bacteria binds to ciliated wpithelium
- secretes PTx which alters adenylate cyclase activity
- ADP ribosylates Gia which induces elevated cAMP production resulting in increased secretions and mucus production
- other secreted factors damage the mucociliary elevator
What are the important features of corynebacterium?
gramstain/ morphology
virulence factor
anatomical location of infection
population of infection
is there a vaccine
- gram positive arranged in pallisades (unsual organization of bacteria)
- virulence factor is diptheria toxin (DTx): ADP-ribosylates EF-2 (inhibits protein synthesis)
- produces pili required for bacterial colonization of upper RT
- global distribution but uncommon in US and other developed areas due to vaccine
What diseases are associated with corynebacterium?
how is the diease primarily mediated?
Psuedomembrane: non-toxin producing strains elicit localized infection resulting in pseudomemebrae
Systemic disease: Toxin- producing strains have a toxin carried on a lysogenic (integrated)bacteriophage. symptoms include fever, sore throat, and malaise
**disease is priamrily mediated by production of diptheria toxin**
WHat is the mechanism of disease elicitation for C. diptheriae?
- pili mediate adherence of bacteria to repiraotry epithelium
- extensive bacterial replication at surface of epithleium
- 2 stages: localized invasion and systemic disease (toxin producing strains)
What is the pseudomembrane assciated with C. diptheriae made up of?
fibrin, bacteria, and inflamamtory cells
What is the diptheriae vaccine composed of?
formalin inactivated diptheria toxin (diptheria toxoid)
because of the vaccine diptheria associated morbidity and mortality has been greatly reduced
What bacterial vaccine is commonly used as a conjugate for other vaccines?
Diptheria!
DT-also carrier for conjugate vaccines (Hib)-CRM 197 a point mutation within DT that inactivates the toxin
What are the following important features of Neisseria meningitidis?
gram stain and morphology
virulence factors
anatomical location of inhabitance
- gram negative diplococci
- oxidase+, catalase+, polysaccharide capsule, and produce pili
- common inhabitant of the nasopharynx of healthy individuals (most often teens)
What diseases are associated with Neisseria Meningitidis? What population is most often infected? What is the greatest concern?
Pharyngitis, Pneumonia (able to cause lower resp infection when aspirated)
usually preceded by respiratory tract infection. often seen in individuals with underlying disease or in kids
greatest cncern is progression to meningitis
What is the mechnaism of disease elicitation for N. meningitidis?
breaks through the epithelial layer via its virulence factors and avoids phagocytization by PMNs. If it gets to the blood stream can lead to meningitis
What are the 3 virulence factors for N meningitidis? What is the biologic effect of each?
- capsule-prevent phagocytosis and complement fixation
- type IV pili- allow colonization of the nasopharyns
- LOS- lipooligosaccharide: similar to LPS but no repeating O-antigens. Has endotoxin acitivity
Which serogroups is the N meningitidis vaccine developed against? At what age is it adminstered?
The vaccine is against the polysaccharide capsule
- polyvalent vaccine developed against serotypes A,C,Y, W135 administered to individuals >2yrs
- MCV4-conjugate vaccine for <55 yrs
- MPSV4 capsule vaccine >55yrs
What are the important factors for streptococcus pyogenes (Group A Strep)?
gram stain/ morphology
virulence factors
gram positive cocci arranged in chains
beta-hemolytic, catalse negative
Possesses M protein and has a hyaluronic capsule
What diseases are associated with streptococcus pyogenes (GAS)?
Pharyngitis (strep throat): redness and edema of the mucous membranes, fever, purulent exudate, tonsilitis
Scaret fever: streptococcal pharyngitis and an erythematous punctiform rash
What is the mechanism of disease elicitation for S. pyogenes? specifically what leads to scarlet fever?
- Surface proteins (M protein, F protein, ,LTS) promote adherence in pharynx
- Localized tissue destruction due to secreted enzymes
- scarlet fever is secondary complication. due to pyrogenic exotoxins-superantigens, not bacterial dissemination
What are the 7 virulence factors for strep pyogenes and what are thei biologic effects? (I’m sorry to put so much on one card <3)
- Capsule-prevent phagocytosis and complement fixation
- LTA-binds to epithelial cells
- M protein: adhesin; antiphagocytic; degrades complement component C3b
- Pyrogenic exotoxins: mediates pyrogenicity
- Streptolysin S: lyses leukocytes, platelets and erythrocytes
- Streptolysin O: Lyses leukocytes, platelelets and erythrocytes
**phew you made it to the end <3 Go you!
How do we check for streptococcus pyogenes in clinic besides growing a culture?
Rapid Strep Test/ Rapid Antigen Detection Test
membrane on test contains anti-strepA antibody, sample from throat is inserted. a line appears when the antibody on the test combines with the antigens in the sample
WHat are the important features of staphylococcus aureus?
gram stain/ morphology
virulence factors
Gram positive cocci often in clusters
catalase +, polysaccahride capsule, protein A on surface, many different toxins and cytopathic enzymes
What disease is associated with Staphylococcus aureus infection of the RT? How is it acquired and who gets it?
Pneumonia-seen mainly in the very young and elderly with underlying pulmonary disease.
acquired via aspiration of oral secretions or hematogenous spread from a different site
WHat is the mechanism of disease elicitation of S. aureus?
- normal component of nasopharyngeal flora
- pulmonary tissue destruction due to secreted enzymes
- can spread to other infected sites to manifest differes disease symptomology
What are the 3 virulence facotrs for S. aureus and what are their biologic effects?
Capsule: prevent phagocytosis and complement fixation
LTA: binds to epithelial cells (fibronectin)
Protein A: Binds Fc receptors to inhibit antibody-mediated clearance
What are important features of Streptococcus pneumoniae?
gram stain/morphology
virulence factors
is there a vaccine/what is the basis for it
Gram positive cocci often in pairs (diplococci)
alpha hemolytic, polysaccharide capsule in the viruelnt strains
more than 90 different capsular serotypes recognized (basis of vaccine)
note there is no lancefield designation- which means not GAS, GBS etc
What disease is associated with streptococcus pneumoniae infection of the RT?
Lobar pneumoniae, sinusitis, otitis media
What is the mechanism of disease elicitation in S pneumoniae?
lungs fill with fluid due to tissue damage and over-activation of the immune response
What are the 2 virulence factors for S pneumoniae? What are their biologic effects?
Pneomolysin: destroy epithelial cells, activates alternative complement pathway, suppresses phagocytic oxidative burst
Capsule: Antiphagocytic
What does the S. pneumoniae vaccine target? What are the 2 different kinds?
S, pneumoniae vaccine targets the polysaccharide capsule
23-valent polysaccharide capsule vaccine (PPSV23) for adults and at risk adults/kids
13-valent canjugated vaccine (PVC13) for children<2yrs
What are the important features of Haemophilus influenzae?
gramstain/ morphology
requirements for growth
virulence mechanisms
Small Gram negative rods
requires heme and NAD for growth (grows on chocolate agar)
invasive species possess polysaccharide capsule
uses pili and OMPs to bind respiratory epithelial cells
What diseases are associated with infection of H. influenzae in the RT? What strains colonize the upper RT?
Pneumonia, sinusitis, otitis, epiglotitis
non-encapsulated strains colonize upper RT
Lower RT infections more common n kids or individuals with underlysing condition
What is the mechanism of disease elicitation for H. influenzae? What are we worried about?
- attaches to respiratory epithelium through pili and OMPs
- gain access to underlying submucosa by invading between epithelium
- cause induction of localized pro-inflammatory response. concern is systemic infection and spread to CNS
What are the 3 virulence factors for H infleunzae? What are their biologic effects?
Capsule: prevent phagocytosis and complement fixation
OMPs (HMW1, HMW2): Outer membrane proteins-bind to epithelial cells
LOS-: Lipooligosaccharide: has endotoxin activity
Which type of H. influenzae is there a vaccine against? How effective is it?
YES!
- Vaccine to Hib (H. influenzae type B)
- 3 monovalent conjugate vaccines and combination Hib-conjugate vaccines are available
- Hib has decreased in children by 99% since vaccine was introduced
What are the important features of Mycoplasma pneumniae?
morphology/gram stain
aerobe vs anaerobe
virulence factors
- No cell wall (so does not gram stain) coccoid or pleomorphic (egg like appearance)
- bound by triple layered membrane containing sterols
- obligate aerobe
- produces P1 adhesin
- smallest free living prokaryote, lifestyle associate with host cells, slow growing
What diseases are associated with Mycoplasma pneumoniae infection?
Tracheobronchitis and atypical pneumonia
What is the mechanism of disease elicitation for M. pneumoniae?
- associates with upper airway epithelial cells through the major adhesion=P1
- close association causes local accumulation of toxic metabolites, oxidation of lipids
- binding destroys cilia and inhibits clearance by normal mechanisms resulting in shedding of the bacterium in respiratory secretions
- induces inflamamtory response which enahnces cell damage via over-secretion of cytokines
What are the important features of Pseudomonas aeruginosa?
gram stain/ morphology
virulence factors
where do they grow
- Gram negative rod with single polar flagella
- oxidase +
- form in biofilms on surfaces and inanimate objects (catheters)
- opportunistic pathogen
- multiple virulence determinants including exotoxins
What diseases are associated with infection by Psedomonas aeruginosa?
lung infections of cystic fibrosis patients
What is the mechanism of disease elicitation for P. aeruginosa?
- opportunistic=must breach normal host defense barriers
- biofilm formation allows bacteria to resist mmune-mediated clearance
- produces pilins and other adhesins which promote association with repiratory epithelial cells
- produces numerous secreted proteins (proteases, exotoxins, endotoxins, DNAses) which directly damage or inactivate host cells
WHat are the 2 virulence fators for P. aeruginosa?
polysaccharide capsule (alginate): protection from immune system
Exotoxins (ExoA, ExoU, ExoY, ExoS): inactivate or destroy host tissues
What are the important features for Legionella pneumophila?
gram stain/ morphology
who does it infect
virulence factors
how is it grown
- Gram negative rod
- opportunistic pathogen
- single polar flagella
- maintained in water supplies and or amoeba in environment
- grown on special medium
- produces cytotoxins, hemolysins, endotoxins and lipases
- typically detected by fluorescent antibody stain
What diseases are associated with infection by Legionella pneumophila?
Legionaire’s disease: sever pneumonia-like symptoms
Pontiac fever: self-limiting flu like illness
What is the mechanism of disease elicitation of L. pneumophila?
- survives inside alveolar macrophages within lungs
- production of various enzymes (phosphatase, lipase, and nuclease) kills infected host cell
- little is known about what responsible for difference in disease presentation between Legionaire’s and Pontiac fever
What are the important features for Mycobacterium tuberculosis?
gramstain/morphology
contents of cell wall
how does it survive
what kind of infection does it cause
- acid-fast rods (although bacterium is considered gram positive)
- thick waxy cell wall contianing mycolic acids and lipoarabinomannan
- survivies in granulomas
- causes acute or latent infection
What diseases are associated with Mycobacterium tuberulosis?
Tuberculosis (however, various manifestations)
What is the mechanism of disease elicitation by M tuberculosis?
- bacterium survives and persists within host-generated granulomas (latency)
- reactivates to cause acute disease
- disease symptomology primarily over-exaggerates host response to infection leading to tissue necrosis
What are the virulence factors for M. tuberculosis?
Long chain fatty acids (mycolic acids, liparabinomanan): impervious cell envelope helps prevent damage by host compounds (cationic peptides, oxygen radicals, nitric oxide) encountered within granuloma
How do we diagnose M tuberculosis and what is the treatment?
Diagnostic: PPD skin test (delayed type hypersensitivity), quantiferon test-specific to M. tuberculosis infection
Treatment: multidrug cocktail includin isoniazid (targets mycolic acids) administered over extended period
How could infection by influenza Virus A pre-dispose people to bacterial infection?
viral infection disrupts airway epithelium, alters normal mechanical clearance, disrupts phagoctic phagocytic function
What can be done to prevent infection by Streptococcus pneumoniae?
immunize with prenar 13-conjugate vaccine which targets capsule which is a major viruelnce factor
Are you sick of bacteria yet?
Well you’re in luck bc this deck is OVER! <3
