Microbiology review week 4

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Microbiology reviewweek 4

• efking_at_u.washington.edu

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What well cover this week

• Wrap up enterobacterial infections
• Wrap up G- bugs
• Pseudomonas
• Anaerobes
• Sepsis
• Wrap up G bacilli
• Zoonoses
• Spirochaetes

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E. Coli

• Strains that possess K1 capsular antigen
• Neonatal meningitis, sepsis
• Second most common cause of meningitis

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E. Coli K1

• Commonly present in GI/GU tracts of pregnant
  women
• Tranmission to baby during delivery
• Colonizes intestine of neonate
• Invades intestinal epithelial cells, gains access
  to blood
• Invades cerebral endothelial cells
• Antiphagocytic capsule
• Dx CSF, blood culture
• Rx cant wait for culture - empiric antibiotic

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UTIs

• Cystitis - bladder infection can lead to
• Pyelonephritis - kidney infection can lead to
• Bacteremia, sepsis, progressive kidney damage,
  renal failure
• Not all organisms
• Dx UA, leukocyte esterase dipstick test
• Rx cipro, bactrim 3 days for cystitis,
  hospitalization 7 days for pyelonephritis

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Community-acquired UTI bugs

• E. coli - strains in gut flora with
• Fimbrial adhesins - adhere to glycolipids on
  uroepithelium
• Hemolysin - damages RBCs, WBCs
• Aerobactin - siderophore chelates Fe
• S. saprophyticus
• Urease
• Klebsiella pneumoniae
• Fimbrial adhesin, antiphagocytic capsule, urease
• Proteus mirabilis
• Urease

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Nosocomial UTI bugs

• Previous slide plus
• Enterococci
• Pseudomonas

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Nosocomial infections

• Hospital acquired
• All Enterobacteriaceae can cause
• Anyone with catheter, IV port etc. susceptible
• UTI
• Wound infections
• Sepsis
• pneumonia

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Nosocomial bugs

• Klebsiella
• Especially aspiration pneumonia in alcoholics
• Enterobacter
• Serratia
• S. aureus
• Pseudomonas

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Sepsis

• Bacteremia bugs in your blood
• Can be asymptomatic, ex. brushing your teeth
• Sepsis bacteremia that causes systemic immune
  response
• Fever, elevated WBC, tachycardia, tachypnea
• Septic shock sepsis that results in hypotension
  not controllable by fluid administration
• Organ dysfunction - ARDS, renal failure, CV
  collapse

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Mechanisms of sepsis

• Lipid A serum LBP TLR4/CD14 on
  monocytes
• sCD14 in serum intracellular
  signalling
• endothelial cell receptors TNF, IL-1
• NO selectins prothrombotic/
  fever
• antifibrinolytic factors
• vasodilation PMN DIC

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Agents of sepsis

• G- organisms
• Lipid A endotoxin
• E. coli, Klebsiella, Enterobacter, Pseudomonas
• G organisms
• Staph, Enterococci
• Fungi
• Candida albicans

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Rx for sepsis

• Supportive
• Fluids
• Ventilation
• Antibiotics
• Recombinant activated protein C (fibrinolysis)

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Question 1

• Lipid A of lipopolysaccharide induces cytokine
  production in monocytes by
• Activation of guanylate cyclase
• Binding to TLR4-CD14 receptors
• Forming ion channels
• Entry into cytoplasm via pore-forming ability
• Stimulation of cytoskeletal actin polymerization

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Question 1

• Lipid A of lipopolysaccharide induces cytokine
  production in monocytes by
• Activation of guanylate cyclase
• Binding to TLR4-CD14 receptors
• Forming ion channels
• Entry into cytoplasm via pore-forming ability
• Stimulation of cytoskeletal actin polymerization

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Pseudomonas aeruginosa

• G- rod
• Obligate aerobe
• Non-lactose fermenter
• Oxidase
• Green pigmented colonies, smells like grapes
• Opportunist - infects sick, immunocompromised
  patients
• Innate or acquired resistance to almost every
  antibiotic

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Pseudomonas

• Requires break in epithelium
• Adhesins - adheres to extracellular matrix
• Antiphagocytic capsule
• Exotoxin A
• ADP ribosyl transferase, targets EF2 stops host
  protein synthesis (Where have we seen this
  before?)
• Exoenzyme S
• ADP ribosylates Ras
• GTPase activating activity - Rho, Rac, CDC42
• Disrupts cytoskeleton, cilia

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Pseudomonas

• Pneumonia - especially cystic fibrosis,
  immunocompromised pts
• Otitis externa
• Hot tub folliculitis
• Eye infections (contact lenses)
• Burn wound infections - sepsis
• UTIs
• Endocarditis
• Osteomyelitis - especially from diabetic foot
  ulcers

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Anaerobes

• G G -
• Rods cocci rods
• Spore formers
• peptostreptococcus Bacteroides
• Prevotella
• Anaerobic Fusobacterium
• Clostridium

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Bacteroides fragilis

• intra-abdominal abscess (leading cause)
• Low grade fever, abdominal pain
• Soft tissue, skin infections
• Mild diarrhea in kids
• Enterotoxin - low toxicity
• Acquire from colonic flora
• Capsular polysaccharide
• Rx combination antibiotics, drainage

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Prevotella

• Normal flora of mouth -
• Periodontal disease
• Aspiration pneumo, lung abscesses
• Chronic sinusitis, otitis
• Brain abscesses
• Capsular polysaccharide
• Rx antibiotics

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Fusobacterium

• Hand infection
• Neck infection
• Lung infection
• Often mixed with Bacteroides, Prevotella
• Oral flora

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Peptostreptococcus

• G cocci in chains
• Anaerobe
• Catalase
• Pleural/pulmonary infections
• Interabdominal abscesses
• Pelvic infections
• Often mixed with Bacteroides, Prevotella

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Question 2

• Which property of Bacteroides fragilis is
  associated with abscess formation?
• Sporulation
• Endotoxin
• Capsular polysaccharide
• Adhesive fimbriae
• Phospholipase

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Question 2

• Which property of Bacteroides fragilis is
  associated with abscess formation?
• Sporulation
• Endotoxin
• Capsular polysaccharide
• Adhesive fimbriae
• Phospholipase

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Clostridium spp.

• G spore-forming rods
• Anaerobic (vs. Bacillus)
• Pathogenisis via powerful exotoxin, enzyme
  secretion
• Dx (unless otherwise stated) - demonstrate toxin

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C. perfringens

• Gas gangrene
• Spores/bacteria enter necrotic area, multiply
• Release toxins, gas
• Sx sudden pain tense, edematous skin -
  crepitance
• Shock, renal failure, coma death can ensue
• Rx debridement, penicillin, hyperbaric O2,
  antitoxin
• Food poisoning
• Caused by enterotoxin
• Meat products
• Bug can survive cooking
• No fever, rare vomiting diarrhea, nausea, abd
  pain

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Gas gangrene
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C. perfringens

• Found in soil, colonic flora
• Resistant to boiling, disinfectants
• ? toxin - phospholipase C ? necrotic
• ? toxin - O2 labile hemolysin area
• Enterotoxin - pore-forming
• produced during sporulation

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C. botulinum

• Botulism
• Sx onset 12-36 hours after ingestion of toxin
• Botulinum toxin blocks ACh release at NMJ
• Heat labile
• Descending symmetrical weakness - diplopia,
  dysphagia, general weakness, respiratory
  paralysis
• Rx antitoxin to neutralize free toxin in blood
  respiratory assistance
• Spores in soil, ponds lakes
• Transmitted by home canned foods

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C. botulinum

• Infant botulism
• spore ingestion - germinate, colonize colon
  secrete toxin
• Honey
• floppy baby
• Wound botulism
• Colonization toxin secretion Sx similar to
  food poisoning
• Cocaine users

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C. tetani

• Tetanus spastic paralysis
• Spores introduced by trauma grow in necrotic
  tissue, secrete toxin
• Toxin moves retrograde via motor neurons to CNS
• Prevents inhibitory interneuron neurotransmission
  - tetany
• Lockjaw, risus sardonicus

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C. tetani

• Found in soil, feces, lower GI tract
• Dx cannot culture
• Rx antitoxin
• antibiotics not helpful.
• Supportive therapy
• Toxoid vaccine

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C. difficile

• Pseudomembranous colitis
• Diarrhea, cramps, fever
• Follows broad-spectrum antibotic Rx that wipe out
  normal flora
• FYI - cephalosporins, clindamycin, ampicillin
• Exotoxins
• Toxin A - enterotoxin fluid secretion
• Toxin B - cytotoxin glycosylates Rho A GTPase
  (regulates actin)

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C. difficile

• Can be member of normal flora
• 60 newborns
• 3 adults
• Nosocomial outbreaks
• Rx antibiotics

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Question 3

• Causes antibiotic-associated colitis through the
  production of toxins that glycosylate Rho GTPase
• Clostridium perfringens
• Bacteroides fragilis
• Prevotella melaninogenica
• Clostridium difficile
• Salmonella enterica non-typhi

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Question 3

• Causes antibiotic-associated colitis through the
  production of toxins that glycosylate Rho GTPase
• Clostridium perfringens
• Bacteroides fragilis
• Prevotella melaninogenica
• Clostridium difficile
• Salmonella enterica non-typhi

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Biological weapons zoonoses
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Bacillus anthracis

• Aerobic spore-forming G rod
• Cutaneous anthrax
• Spores introduced into skin multiply, exotoxin
• Erythematous papule - vesicle - ulcerates -
  eschar
• Lymphadenopathy, edema
• 10-20 - bacteremia, systemic disease
• GI anthrax
• Ingestion of meat contaminated with spores
• Matures, replicates, releases exotoxin
• Nausea, vomiting, diarrhea
• Rare, often fatal

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B. anthracis

• Pulmonary anthrax
• Inhalation of spores incubates 2-43 days
• Taken up by alveolar macrophages
• Germinate in hilar, mediastinal nodes
• Initial fever, cough, dyspnea, emesis,
  diaphoresis
• Fulminant phase high fever, dyspnea, pleural
  effusion, shock, death

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B. Anthracis

• Antiphagocytic capsule
• Toxins
• PA (protective Ag) - promotes entry of LF EF
  similar to B unit of A-B toxins
• LF (lethal factor) - Zn metalloprotease
  increases cytokine production, macro lysis
• EF (edema factor) - adenylate cyclase toxin
  increases cAMP, causes edema
• Dx CXR - wide mediastinum G/culture vesicle
  fluid
• Rx 60 days antibiotics, drain pleural effusions
• Vaccine acellular
• No person-person spread

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Yersinia pestis

• G- rod
• Oxidase -
• Non-lactose fermenter

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Y. pestis

• Bubonic plague
• Buboes
• Painful lymphadenopathy
• Bacteremia
• Fever, HA
• Seeding of lungs, liver, spleen, meninges
• Endodoxic shock

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Y. pestis

• Bubonic plague
• Transmitted by bite of infected flea
• Multiply in fleas gut
• Flea pukes on you when it tries to feed
• Secondary person-person spead by aerosols
• Resists phagocytosis via type III secretion
  system
• Suppresses cytokine production
• Cytotoxin - messes up actin, initiates apoptosis

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Bubo
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The black death
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Y. pestis

• Primary pneumonic plague
• Fever, malaise, chest tightness
• Cough, cyanosis
• Invariably fatal
• Dx G stain bubo aspirate, blood fluorescent Ab,
  serology
• Rx early antibiotics

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Francisella tularensis

• Ulceroglandular tularemia
• Infected by bite of tick/flea/deerfly low
  infective dose
• Handling of rabbit carcasses
• Papule - ulcerates
• Regional lymphadenopathy
• Fever, chills, HA, rigor, sore throat
• Sort of like bubonic plague with a sore, less
  death

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Ulceroglandular tularemia
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F. tularensis

• Pneumonic tularemia
• Inhalation of aerosolized bacteria or
  hematogenous spread from skin low infective dose
• Oculoglandular - via contact with eyes
• Typhoidal tularemia
• Ingestion of large of organisms
• No skin lesions/nodes fever, abdominal pain

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F. tularensis

• No human - human spread
• Dx fluorescent Ab
• Rx antibiotics relapses possible
• Antiphagocytic capsule
• Survives inside macrophages
• Inhibits phagosome-lysosome fusion

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Brucella spp.

• Brucellosis
• GU pathogen of domestic animals
• acquire from infected meat, unpasteurized dairy
• Penetrates through skin cuts, inhalation or
  ingestion
• Intracellular growth in phagocytes
• Phagocytosed, prevent PMN degranulation
• Lymphatic spread
• Form granulomas - degraded - return to
  circulation
• Undulating fevers, HA, anorexia, weight loss
• Rx antibiotics 6 weeks relapses common

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Pasteurella multocida

• G- coccobacillus
• Colonizes URT cats, dogs infection following
  cat/dog bites, scratches. High risk with
• Chronic liver disease
• Chronic pulmonary disease
• Prosthetic joints
• Skin, soft-tissue infections
• Osteomyelitis
• Respiratory tract infections
• Dx culture
• Rx antibiotics, wound care

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Capnocytogapha canimorsus

• G- rod
• Colonize dog/cat gingiva
• Wound infections following dog bite
• Overwhelming sepsis DIC
• Asplenic individuals
• Compromised hepatic function
• Corticosteroid Rx
• Dx culture
• Rx antibiotics (prophylaxis for dog bites),
  supportive

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Spirochaetes

• Tiny, G- (if stain at all)
• Hard to Dx - cant see well by LM
• Darkfield microscopy, immunofluorescence
• Cannot be cultured on ordinary media some not at
  all
• serology
• Spinning motility

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Leptospira interregans

• Anicteric leptospirosis
• Leptospiremic phase
• Invade blood, CSF - spiking fevers, HA, myalgia,
  red conjunctiva, photophobia
• Brief asymptomatic period
• Immune phase
• IgM Abs show up
• Aseptic meningitis, conjunctival hemorrhage
• Icteric leptospirosis - 10 mortality
• Progression to jaundice, renal failure

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Leptospira

• Found in domestic animal pee
• Entry via skin abrasion, mucus membrane
• Vascular damage - symptoms
• Rx antibiotics, dialysis
• Killed whole cell vaccine

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Borrelia burgdorferi

• Lyme disease
• Stage I localized infection, erythema migrans
• Stage II disseminated infection
• Neurological abnormalities occasionally persist
• Stage III persistent infection
• Recurrent arthritis, occasional neuro disorder

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B. burgdorferi

• Bite of Ixodes tick (hard bodied)
• Reservoir mice, deer
• Animal - human, human - human
• Common in NE U.S. in summer/fall
• Migration in skin from entry site
• Decorin - adheres to ECM
• Induces cytokines, autoimmunity
• Dx ELISA, Western blot
• Rx antibiotics 30-60 days IV 30 days for neuro
  dz
• Subunit vaccine

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Borrelia hermsii/recurrentis

• Relapsing fever
• Incubates 1 week
• Sudden onset high fever, HA, weakness,
  hepatosplenomegaly - crisis
• Recovery 5-7 days
• Relapse X10
• Lipoproteins induce cytokines
• Ag variation by DNA rearrangement
• Dx visualize in blood smear (stain well)
• Rx antibiotics can produce crisis

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B. hermsii/recurrentis

• B. hermsii
• Soft tick born carried by rodents
• W. US
• B. recurrentis
• Louse-born
• Epidemics, human-human spread via lice
• Not in US
• More severe disease

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Treponema pallidum

• Primary syphilis
• Indurated, painless ulcer at inoculation site 3-6
  weeks after contact resolves weeks-months
• Secondary syphilis
• 2-8 weeks after initial lesion systemic
  infection
• Rash all over, including palms, soles
• Condyloma latum - wart-like, can ulcerate
• Fever, malaise, HA, anorexia
• Latent
• Asymp or relapses of secondary Sx for 4-5 years

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T. pallidum

• Tertiary syphilis - about 1/3 of unRx pts
• Neurosyphilis
• Meningovascular - paralysis, weakness (5-10 yrs)
• Parenchymatous - insanity (15-20 yrs)
• Tabes dorsalis - spinal cord demyelination
  ataxia (25-30 yrs)
• Cardiovascular syphilis - Ascending aorta (cause
  of death)
• Gumma - granulomas in skin, organs

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T. pallidum

• Congenital syphilis
• Transplacental infection - many abort
• Doesnt damage fetus until 4th month gestation
• If healthy at birth, develop Sx in 2-3 years
• Ocular Sx - corneal inflammation
• Gumma
• Skeletal deformities

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T. pallidum

• Entry via skin lesions, mucus membranes
• Enter circulation - systemic spread
• Microvascular damage
• Dx
• Screening test VDRL/RPR if then do
• Specific testFTA, MHA-TP
• Rx penicillin
• Primary/secondary 1 dose!
• Latent 3 doses
• Neurosyphilis 2 weeks

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Question 4

• Which of the following can be acquired by
  ingestion, inhalation, bites from ticks and
  fleas, and skin abrasions?
• Tularemia
• Plague
• Anthrax
• Botulism
• Brucellosis

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Question 4

• Which of the following can be acquired by
  ingestion, inhalation, bites from ticks and
  fleas, and skin abrasions?
• Tularemia
• Plague
• Anthrax
• Botulism
• Brucellosis

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