Gram negative Flashcards
Nosocomial infections
Hospital acquired infections Factors: - surgery, procedures - indwelling devices - ex UTI - chronically ill, immunosuppression - use of antibiotics - disrupt normal microbiome Sources: - vectors (neckties, hands) - patient's own skin
“Opportunistic” infection
Causes disease only in “compromised” patients
- immune fx (AIDS, chronic disease, suppression)
- innate protective mechanisms (ex CF -> mucociliary clearance)
- physical barriers (cut, hot tub)
Widespread in env’t
- less specialized to human host
Should be preventable!
Virulence factors: LPS (-> inflammatory response), adhesins, nutrient acquisition, toxins
Opportunistic antibiotic resistance
Frequently carry antibiotic resistance
Intrinsic
- natural competition with antibiotic producers in soil environment
- Pseudomonas aeruginosa, Acinetobacter baumanii, Burkholderia
Acquired - increased resistance in ICU
Biofilms - significantly enhances resistance
Can’t develop resistance to soap!
Biofilms
Surface-associated cells + extracellular matrix
May be single or multi-organism
Can occur quickly in the right environment
- ex lung, heart valves -> endocarditis, catheters
- high availability of nutrients (ex parenteral nutrition)
Active dispersal from biofilm -> blood-stream infection
Resistance to antibiotics - both diffusion and specific induction of genes (ex protective polysaccharide coating)
Quorum sensing - detect high density of similar organisms -> induce virulence factors
E coli as opportunistic pathogen
Most common opportunistic infection!
E coli strains that are normally commensal ->
UTI
Meningitis
Bacteremia
Common virulence = toxins, capsule, pili
vs specialized strains -> gastroenteritis
Uropathogenic E coli (UPEC)
95% of all non-nosocomial UTIs
Women (anatomy, intercourse), catheters
Few serogroups
- different strains -> different adhesins and pili allow colonization
Ascending route: ureter -> cystitis (dysuria, urgency) -> pyelonephritis (flank pain, fever)
“Bacteruria” > 10’5/mL (lower levels don’t count because part of normal microflora)
Self limiting, antibiotics for pyelonephritis
Recurrent infection due to re-entry or biofilm in urothelium -> re-emergence with stress
UPEC virulence factors
Adhesion is necessary for colonizing -> invasion of urothelium
- > biofilm on catheter, “pods” replicating in epithelium
- measure with hemagglutination assay (+ mannose)
P pili -> Gal-Gal glycolipids on RBC’s, urothelium
- Gal-Gal is P1 blood group -> more UTI’s
- > pyelonephritis
Mannosides/mannoproteins - on urothelium, bound by many E coli structures
- if binding is blocked by additional mannose -> mannose sensitive (MS)
- ex MS - Type 1 pili -> cystitis
- not blocked by mannose -> resistant (MR)
- ex MR - Prs pili, S pili, Dr adhesin -> cystitis; F adhesin -> pyelo
Other factors: LPS, capsule, motility, exotoxins
E coli bacteremia
Leading nosocomial bacteremia
UTI, catheter -> invades urothelium
- common if UTI + urinary obstruction
Similar strains to UTI
K1 capsule -> serum resistance (blocks complement -> escapes phagocytosis)
- polysialic acid (sim to Neisseria meningititis)
- similar to host glycoproteins -> no immune response
- 20-40% prevalence of E coli K1
Severe inflammatory response due to LPS
E coli meningitis
Newborns!
Colonized -> bacteremia -> CSF (mechanisms unclear)
K1 capsule - escapes phagocytosis
- 20-40% prevalence (vertical transmission from mother)
Siderophores - chelation may be useful therapy
Hemolysin
Overview of Gram (-) opportunistic
E coli (UTI, bacteremia, meningitis) Pseudomonas aeruginosa Klebsiella pneumoniae Enterobacter cloacae Serratia marcesens Proteus vulgaris, Proteus mirabilis Acinetobacter
Pseudomonas aeruginosa
Wide range of sites: burns, eye, catheters, devices, urinary
Pneumonia (esp ventilator aka VAP)
Bacteremia if compromised
Virulence: LPS T3SS-secreted exotoxins: - ExoA - inhibits protein synthesis - ExoS, ExoT - enzyme, modifies cell regulation - ExoU - phospholipase -> surfactant Elastase -> lung connective tissue Pyocyanin toxin -> cell produces ROS - also blue-green -> "aeruginosa" - only produced by colonies after quorum sensing Capsule Pili
Obligate aerobe - grows only in aerobic culture
- technically can use nitrate ETC, ferment Arg
Lots of antibiotic resistance
Chronic Pseudomonas
Cystic fibrosis -> biofilm, chronic infection (80% prevalence)
- mutates -> produces alginate slime -> resists phagocytosis
- decline due to immune response (bacterial load constant)
- never eliminated, manage with antibiotics
Pseudomonas also chronic in COPD
CF - also susceptible to Burkholderia cepacia complex = deadly
Klebiella pneumoniae
Pneumonia - esp chronic medical (ex alcoholism -> aspiration) -> red currant jelly UTI Wounds Bacteremia, meningitis possible Diarrhea (enterotoxic strains)
Virulence from capsule
- resists complement, phagocytosis
- identification via mucoid colony morphology
Toxins (specific strains)
Enterobacter cloacae
Normal gut flora -> burns, wounds, repiratory, UTI, catheters
Unknown virulence factors (makes biofilms)
- O, H, K antigens
- some strains make toxins
Similar to Klebsiella but motile, less heavily encapsulated
Often nosocomial, after antibiotic therapy (resistance!)
ex - epidemic from infected catheter insertions (E. cloacae and E. agglomerans)
Serratia maracens
Common in env’t
- prodigiosin = red pigment (competition with fungi)
Less GI colonization but reservoir in infants
Respiratory (ex respiratory -> pneumonia)
Urinary
Septic arthritis
Often after broad-spectrum antibiotics
Instrumentation - ex heroin addicts
Virulence:
Swarming motility
MS-fimbrae (mannose sensitive), proteases (vs IgG), siderophores
