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131 Cards in this Set
- Front
- Back
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situations that PREDISPOSE one to OPPORTUNISTIC INFECTIONS:
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1) antibiotics
2) surgical treatments 3) indwelling devices 4) chronic illness 5) chemo-immunosuppression 6) immunosuppression due to infection (ie AIDS) |
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How do OPPORTUNISTIC PATHOGENS differ from other PATHOGENS
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these pathogens show LESS SPECIALIZED adaptations to the host than other pathogens
only capable of causing infection when host defenses are compromised |
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NOSOCOMIAL infections
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those that occur in the hospital (hospital-aquired infections)
often multiply (antibiotic) resistant |
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characteristics of GRAM-NEGATIVE OPPORTUNISTIC PATHOGENS
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-Production of VIRULENCE FACTORS
-BIOFILMS -LPS (involved in symptomotology) |
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Virulence Factors
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contribute to the disease caused by the bacterium
(can include variety of different types of molecules, toxins and cell surface structures) |
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factors or pathways that are required for an organism to cause disease
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virulence determinants or pathogenesis
**may not be specific to bacterium-host interactions |
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mechanism by which gram-negative bacteria cause disease
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continues to be elucidated
often the immune response to Gram-negative cell components, such as LPS, cause symptoms |
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BIOFILMS
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surface-attached microbial communities (~65% nosocomial infections are thought to be biofilm-related)
Biofilm formation is particularly relevant in device related infections *biofilm bacteria have increased resistance to a range of antimicrobial agents and are often associated with the production of large quantities of polysaccharides |
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bacteria that causes most gram-negative infections
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E. coli
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types of infections caused by E. coli
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1) GI
2) UTI 3) Bacteriemia 4) Meningitis |
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Opportunistic Gram-negative bacteria causing UTIs
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E. coli
Klebsiella pneumonia **Enterbacter cloacae Proteus mirabilus **Pseudomonas aeruginosa Serratia marcescens Morganella Providencia Citrobacter |
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Opportunistic Gram-negative bacteria causing Respiratory infections
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**Pseudomonas aeruginosa
**Enterbacter cloacae Legionella pneumophila Haemophilus Bordetella |
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3 characteristics of E. coli that contribute to its pathogenicity
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1. CAPSULAR ANTIGEN (known significance in neonatal meningitis)
2. PILI (mediates invasion/adhesion esp in UTIs) 3. EXOTOXIN (principal cuase of GI symptoms) |
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UPEC
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Uropathogenic E. coli
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cause of 95% of all non-hospital aquired UTIs
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E. coli
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frequency of UTIs among american women
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60% have at least one in lifetime
11% have at least one per year |
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Opportunistic gram-negative bacteria associated with infections in burns and wounds
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Klebsiella pneumoniae
Pseudomonas aeruginosa Enterbacter cloacae Legionella pneumophila Haemophilus Bordetella |
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bacteria that:
-is part of our normal flora (0.1% of total enteric bacteria) -synthesizes Vitamin K -protects against other pathogens |
E. coli
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route of UTI caused by UPEC
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ascending route of infection
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why are women more susceptible to UTI than men?
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due to presence of bacteria on the vulvar and perirectal areas and the short length of the female urethra
urethral massage or sex can contribute to infection by bacteria |
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a bacteriurial infection requires what concentration of bacteria in urine?
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10^5 bacteria/ ml urine
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cystitis
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syndrome involving dysuria (burning feeling during urination)
-frequency, urgency, occassionally suprapubic tenderness -typically invovles infection of lower UT (but may include upper UT as well) |
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acute pylenophritis
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results from UTI that has disseminated to the kidney
the clinical syndrome characterized by: flank pain, tenderness and fever, dysuria, frequency and urgency |
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how do most UTIs resolve?
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most are acute and self-limiting
however, 27-44% of infected women will experience at least one recurrence w/in 6 months, despite antibiotic therapy |
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what might contribute to persistant UTIs?
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formation of "pods" or biofilm-like structures that form within epithelial cells of the Urinary tract
UPEC is able to invade epithelial cells and replicate within the cells |
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what influences the location of colonization of Uropathogenic E. coli?
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TYPE OF ADHESIN elaborated by a particular E. coli strain
P pili (MR): pyelonephritis/cystitis Prs pili (MR): cystitis Type 1 pili (MS): cystitis S pili (MR): cystitis F adhesin (MR): pyelonephritis Dr adhesin (MR): cystitis MS= mannose sensitive, MR= mannose resistant |
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how is adherence (such as that involved in UPEC colonization) commonly measured?
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by hemagglutination assay
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almost 100% of these are colonized with bacteria within 3 days
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urinary catheters
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P pili present on UPEC associated with pyelonephritis mediate attachment of bacteria to what?
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P blood group globoseries Gal-Gal constituent of glycolipids present on uroepithelial cells and erythrocytes
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Pap genes (of a chromosomally located operon) encode all of the functions necessary for the biogenesis and function of what system?
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the P pilus system
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What is phase variation and what is its function?
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stochastic switching of a phenotypic trait to provide phenotypic diversity inside and outside the host
-Goal: one varient is better able to survive and proliferate -Controlled by: variety of mechs, strand slippage, methylation, recombination -Influenced by enviro factors (temp, carborn source) |
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Mechanisms that control phase variation
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strand slippage
methylation recombination |
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leading cause of nosocomial bactemia
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E. coli
(usually via urinary route, rarely via GI) |
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2 major routes of E. coli invasion
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indwelling devices and UTI
mechanisms by which it crosses from UT into blood is not known (might invovle ability to invade host cells) |
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bacterimia caused by UTI most often occurs when
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urinary flow is obstructed
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E. coli associated with bacteremia have what critical traits?
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SERUM RESISTANCE (ciritcal and correlated with production of K1 capsule)
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the HALLMARK of GRAM-NEGATIVE BACTEREMIA
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systemic reaction to endotoxin or LPS (perhaps most toxic component of most bacteremic isolates of E. coli and is life-threatening)
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most common neonatal pathogen, leading cause of neonatal meningitis
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E. coli K1
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E coli K1 is isolated from what percentage of healthy individuals?
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20-40%
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how does E. coli colonize in newborns?
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can colonize within hours of birth via vertical transmission from the mom or nursery staff
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Pathogenesis of Neonatal meningitis caused by E. coli K1
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1) colonize host mucosal surfaces
2) translocate ax to bloodstream 3) survive transport through bloodstrem (serum resistance important) 4) cross the blood-brain barrier and survive in CSF 5) proliferate and cause tissue damage |
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virulence determinants of E. coli causing neonatal meningitis
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1) K1 polysialic acid capsule = MAJOR determinant
2) other determinants include S. Fimbriae, siderophores, etc... |
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general characteristics of bacterial capsule
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1) outermost strucutre on bacterial surface
2) typically glycoconjugates 3) allow organism to evade nonspecific host immune defenses 4) primarily an anti-phagocytic mechanism |
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features of the K1 capsule
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1) polysialic acid capsule, nearly identical to that of Neisseria meningitidis
2) sialic acids are constituents of most host glycoproteins and glycolipids, which may explain absence of effective immune response against E. coli K1 |
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what feature of the K1 capsule may play a role in ineffective immune response against E. coli K1?
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made of polysialic acid (also a constituent of most host glycoproteins and glycolipids)
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Main contributor to pathogenicity of Klebsiella pneumoniae
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CAPSULE:
reduced phagocytosis reduced complement susceptibility (can also be used to help id K pneumoniae based on a mucoid colony) |
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how does Enterbacter cloacae differ from Klebsiella pneumoniae?
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E. cloacae is MOTILE and generally less heavily encapsulated
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Enterobacter cloacae infection occurs in what setting?
associated with what type of infections? |
occurs in hospital, 2ndary to antibiotic therapy
associated with burn, wound, respiratory and urinary infections |
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blood group type with increased susceptibility to E. coli UTIs and pyelonephritis
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P1 blood group individuals (express P1 determinants in uroepithelium) appeart to be predisposed relative to P2 individuals
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Serratia marcesens infections are seen secondary to what?
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infections are seen secondary to:
-BROAD SPECTRUM ANTIBIOTIC THERAPY or -INSTRUMENTATION (tracheotomy, catheter, etc..) pneumonia often contracted after use of contaminated respirator |
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How is Serratia marcesens different from other enterobacteriaceae?
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less likely to colonise the GI tract and more associated with respiratory and urinary tract than other enterobacteriaceae
(GI tract is important reservoir among neonates) |
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outside the hospital setting, this bacteria has been associated with heroin addicts
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SERRATIA MARCESENS
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in out-patient setting serratia marcesens is associated with what condition?
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Septic arthritis
(also pink stuff in shower) |
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characteristics of Serratia marcescens that may influence its pathogenicity
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production of Ig-specific protease
swarming motility |
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Prodigiosins produced by Serratia give rise to
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a characteristic color
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Proteus vulgaris and Proteus mirabalis are a frequent cause of what type of infection?
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UTI
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2 characteristics of Proteus vulgaris and Proteus mirabalis pathogenicity
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FLAGELLA
UREASE SYNTHESIS (causes accumulation of ammonia) |
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bacteria that synthesizes UREASE, contributing to pathogenesis
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Proteus vulgaris and Proteus mirabalis
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P. aeruginosa acute infections include:
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1) bacteremia in immunosuppressed
2) eye infections 3) burn infections |
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chronic infections by P. aeruginosa generally occur where? associated with what?
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generally occur in the lung
in association with respiratory disease (eg CF) or implanted medical devices |
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bacteria that grows in biofilms in CF patients
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p. aeruginosa
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how is p. aeruginosa detected in blood culture?
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requires aerobic incubation (since cannot ferment sugars= obligate aerobe) can grow via anaerobic respiration with nitrate as an electron acceptor, or ferment the amino acid arginine
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factors that contribute to P aeruginosa pathogenicity:
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1. Grows readily under various conditions (few nutrients, low temps)
2. Endotoxin 3. Plasmid content (antibiotic resistance) 4. Exotoxin- cytotoxic exotixin (ExoA,S,T, and U) 5. Elastases and phospholipases 6. Alginate capsule slime may block phagocytosis in chronic infections 7. biofilm formation ** Pili (type IV) = important virulence factors |
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Exotoxins involved in P aeruginosa pathogenicity
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ExoA: ADP-ribosylates EF-2, stops protein syntehsis and elicits apoptosis
ExoS&T: ADP-ribosylating enzymes that target host regulatory proteins ExoU: cytotoxic, phospholipase activity; causes irreversible cell-membrane damage and rapid necrotic death |
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Exotoxin: ExoA
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ADP-ribosylates elongation factor 2 (EF-2), which stops protein synthesis and elicits apoptosis of affected cells
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Exotoxins: ExoS and ExoT
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ADP-ribosylating enzymes that target host regulatory proteins
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Exotoxin: ExoU
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cytotoxic, has phospholipase activity; causes irreversible damage to cellular membranes and rapid necrotic death
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Legionella pneumophila was first identified where/when
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19776, outbreak of penumonia among American Legion conference attendees
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characteristics of 1976 Legionella pneumophila outbreak
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1. large population (>189 people) affected
2. geographically circumscribed 3. significant mortality (15%) 4. large population at risk, elderly 5. Well publicized |
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characteristics of Legionella pneumophila organism:
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-strict growth requirements, slow growing, rarely isolated from patients, in nature found in water of cooling towers
-resides within amoeba (or free-living in biofilms) -gram negative pleomorphic rod -intracellular growth |
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Legionella pneumophila route of infection
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airborn route from environmental contamination (not usually person to person)
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Legionella pneumophila incubation period
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2-10 days
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most infections caused by Legionella pneumophila are:
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probably clinically insignificant (cold-symptoms)
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why do most Legionella pneumophila outbreaks occur in summer and early fall?
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because AC and heating units are a common reservoir
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in early stages of Legionella pneumophila infection what is induced in M0s and alveolar epithelial cells
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Legionella pneumophila induces apoptosis in M0s and alvelolar epithelial cells
2nd phase of necrosis induced by a pore-forming activity takes place in infected human phagocytes |
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principal clinical symptom in serious cases of Legionella pneumophila infection
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PNEUMONIA
fever, chills and a cough that may be dry or produce sputum difficult to distinguish Legionnaire's disease from other types of pneumonia by symptoms |
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test of choice to Dx Legionnaires disease
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DIRECT FLUORESCENT Ab TEST to id organism
most useful tests detect the bacteria in sputum, find Legionella antigens in urine samples, or compare Ab levels to Legionella in 2 blood samples obtained 3-6 weeks apart |
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how are gram-negative opportunistic pathogens differentiated in the clinical laboratory
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since most are facultative anaerobes, they are distinguished by:
*their ability to ferment lactose |
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lactose fermenting gram-negative opportunistic pathogens
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E. coli
K pneumonia Enterobacter cloacae |
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Enterohemorrhagic E. coli
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O157:H7 (as foodbourne pathogen)
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Surface determinants of E. coli
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O-antigen: LPS
H-antigen: Flagella (peritrichous) K antigen: Capsule |
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Virulence factors of intestingal pathogenic E. coli isoaltes:
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Adhesins
Toxins LT and ST; Shiga-like toxins Endotoxin (LPS) Nutrient update systems (siderophores) Hemolysins and cytotoxins K1 capsule |
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virulence factors of E. coli are typically chromosomally encoded, except for:
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heat labile toxin (LT) and head stable toxin (ST) which are generally encoded on plasmids
Shiga-like toxin is encoded on a lysogenic phage similar to phage lambda |
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Adhesins involved in E. Coli colonization
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FIMBRIAL
{colonization factor antigens (CFAs) and bundle forming pili (BFP)} and NONFIMBRIAL |
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E. coli's H-antigen
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pertrichous Flagella
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epidemiology of E. coli:
Primary source: other sources |
Contaminated Farm products
Primary source: cattle fecal contamination Ground beef, undercooked hamburger, leafy vegetables, unpasteurized juice, dairy, vegetable products 2ndary person to person spread via pools petting zoos, etc.. |
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clinical manifestations of E. coli infections
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asymtomatic carrier
diarrhea, frequently bloody severe cramping abdominal pain vomiting (50% of cases) Hemolytic uremic syndrome (HUS) {~7% of cases: hemolytic anemia, thrombocytopenia, acute renal failure, esp. susceptible: toddlers and eldery} |
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O antigen 157
H antigen 77 |
E. coli O157:H7
s[ecofoc serogroup based on LPS and flagellear antigens |
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Colonization factors of E. coli O157:H7
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Intimin/Tir
delivered by the Type III secretion system attaching and effacing lesion |
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A college student comes into the clinic complaining of eye irritation. This individual wears contact lenses. Culture of the eye reveals a Gram negative rod that produces a greenish pigment and grows at 42C.
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Pseudomonas Aeruginosa
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An individual who was using a urinary catheter subsequently complains of discomfort urinating. Culture reveals a Gram-negative, motile rod.
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E. coli
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Elderly individual returned from college reunion. Complains of flu-like symptoms, but recovers quickly upon antibiotic treatment. No patient samples are culture positive.
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Legionnaires Disease
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Enterohemorrhagic E. coli (EHEC)
infects what organ? |
large intestine
Bloody diarrhea -Organism invades mucosal cells but does not become systemic -Although the organism does not become systemic, the toxins can spread -Hemolytic uremic syndrome (HUS) acute renal failure caused by Shiga-like toxin |
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Enteropathogenic E. coli (EPEC) infects what organ?
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small intestine
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Enteroaggregative E. coli (EAEC) affects what organ?
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small intestine
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Enteroinvasive E. coli (EIEC) affects what organ?
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large intestine
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Enterotoxigenic E. coli (ETEC) affects what organ?
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small intestine
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Forming attaching/effacing lesions (E. coli pathogenesis)
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Type II seretion system (proteins to host cells)
LEE (locus of enterocyte effacement, creation of pathogenicity island) Intimate attaching: Tir intimin complex Effacing: destruction of host cell microvilli |
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Type III Secretion Systems
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A type III secretion system is a specialized form of secretion wherein a protein moves across the bacterial cytoplamic and outer membrane AND across a host cell membrane
A type III secretion system allows the bacterium to deliver proteins to the host cytoplasm |
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Type III Secretion system:
likely evolved from what apparatus? can translocate what? requires direct contact with what? |
Likely evolved from the flagellar export apparatus
The type III secretion system can translocate many different types of effectors Requires direct contact with the host cell |
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Type II secretion system is found only in what type of bacteria?
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-only in gram negatives (but not in all species or strains)
- to date, only found in plant and animal pathogens -usually present on mobile genetic elements (plasmids and transposons) in pathogenicity islands |
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how is the Type II secretion system regulated?
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by low calcium
and by cell contact |
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LEE (Locus for enterocyte effacement)
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the pathogenicity island that encodes the T3SS, intimin, and tir
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the 2 components to type III secretion systems
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"secretion apparatus" used to deliver
"effector proteins" to the host cell altering its biology {Tir, Intimin, other proteins involved in recruitment/transduction) |
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Toxin
-also called verotoxin -encoded on a phage -comprised of 2 subunits -interferes with protein syntehsis via its RNA cleavage activity (subunit A) and may impact cytoskeleton (subunit B) |
Shiga-like toxin
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EspA forms what?
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type III filaments
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EspB and D from what?
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pores in eukaryotic membranes
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Mechanims by which E. coli alters/ subverts host cell biology
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by causing actin polymerization and pedestal formation
(via Intimin on E coli binding Tir on host cell) |
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origin of shiga-like toxin virulence
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bacteriophage?
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Functions of Shiga-like toxin
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Subunit A: interferes with protein syntehsis via its RNA cleavage (RNAse) activity (A subunit)
Subunit B: may bind to lipid component of euk cell membrane, remodels cytoskeleton and redistributes actin-binding proteins |
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Shiga-Like Toxin receptors
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Binds to Gb3/CD77 glycolipid receptor
difference between cattle and humans? |
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RTX or hemolysin
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pore forming protein that inserts into host cell membranes
common in strains of E coli that cause meningitis |
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Emergence of O157:H7 can be explained by
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HORIZONTAL EVOLUTION
O55:H7 (frequent cause of infantile diarrhea, acquired additional virulence factors; Type III Secretion machinery, Intimin, effector proteins, Shiga Toxin (phage encoded) and hemolysin ( |
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type of E. coli
causes Bloody diarrhea Organism invades mucosal cells but does not become systemic Does not possess Shiga toxin, HL or ST toxins Rare |
ENTEROINVASIVE E. coli (EIEC)
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causes Childhood diarrhea similar to EPEC
Somewhat more aggressive than EPEC due to different colonization factors that lead to more aggressive epithelial cell attachment Roles of toxins not known |
EAEC Enteroaggregative E. coli
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Traveler's Diarrhea
Virulence factors include plasmid encoded: fimbriae (colonizes the small intestine) heat-labile toxin (LT) (with essentially the same structure as cholera toxin) heat stable toxin (ST) |
Enterotoxigenic E. coli (ETEC)
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ETEC Exotoxins
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Heat Labile toxin (LT)
heat stable toxin (ST) |
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Heat-Labile Enterotoxin (HL (?LT))
produced by ETEC |
-similar to cholerae toxin
causes a watery, bloody diarrhea -target is adenylate cyclase: leads to increased cAMP levels resulting in excess chloride ion secretion and blocking of Na ion uptake -overall consequence of these physiological changes is a net loss of fluid and electrolytes into lumen of the gut |
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Heat-stable toxin
produced by ETEC |
alters cGMP levels with similar outcome to the heat-labile enterotoxin
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main virulence factors of EHEC
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-Intimin/Tir pedestals, Shiga-like toxin, hemolysin, evolved from EPEC
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main virulence factors associated with EPEC pathogenesis
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-Intimin/Tir pedestals, toxins?
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main virulence factors associated with EAEC pathogenesis
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-No A/E lesions, heat stable toxin, hemolysin
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main virulence factors associated with EIEC pathogenesis
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-non-fibrial adhesins
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main virulence factors associated with ETEC pathogenesis
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LT and ST toxins
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Diagnosis of E. coli infection:
biochemical id based on: |
carbohydrate fermentation patters and other reactions
-lactose fermentation is notable among intestingal pathogens E. coli is Lac +, easily discerned on EMB or MacConkey agar, whereas salmonella and shigella are Lac - |
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-Sorbitol MacConkey Agar Dx test for O157:H7
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O157:H7 is sorbitol-negative (colorless), while commensal E. Coli stains are sorbitol-positive
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Serological Dx for O157:H7
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direct or latex agglutination tests (to id O157 Antigen)
or H7 serological analysis |
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Dx of other diarrheagenic E. coli
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serotyping-pulsed field gel electrophoresis
PCR analysis for virulence factors (e.g. BFP) |
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causes 73,000 cases of infection and 61 deaths each year on average in the US.
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E. Coli
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factors contributing to emergence of infectious diseases caused by foodborne pathogens
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-HUMAN DEMOGRAPHICS: industrialized nations, advancing age (nursing homes), underlying chronic disease (HIV)
-BEHAVIOR (fresh fruit/veggie consumption, eating away from home) -INDUSTRIAL TECH (mass produciton and bredding facilities) -TRAVEL -MICROBIAL ADAPTATION (including resistance) -ECONOMIC DVPT/LAND USE (manure disposal) -BREAKDOWN of PUBLIC HEALTH INFRASTRUCTURE |
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How could switching to hay 5 days before slaughter could reduce E. coli numbers significantly?
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grain produces a low pH in the rumen and this pre-adapts E. coli to smoach acid shock- they survive better
Hay leads to a higher pH, no adaptation and lower survival Problem: switching to hay lowers yield and the beef industry opposes this |
