Gram Positive Bacteria Flashcards
1
Q
What is a superantigen?
What biological and physiological effects does a superantigen have?
A
A substance that causes proliferation of entire subsets of T cells (those w/ T cell receptors w/ specific Vß domains)
Large amounts of cytokines such as IL-1 and TNF are released
Cytokines cause fever, shock, and organ failure
2
Q
What are the steps in pathogenesis?
A
- Enter the host
- Adhere to the host
- Multiple, persist, damage the host (invade into cells, secrete toxins, evade immune response)
- Spread to next host sometimes
3
Q
What are Staphylococci?
A
Gram-positive cocci that grow in grape-like clusters
4
Q
What are the three medically important staphylococci?
A
- Staphylococcus aureus
- Staphylococcus epidermidis
- Staphyloccocus saprophyticus
5
Q
What is important about Staphylococcus saprophyticus?
A
Staphylococcus saprophyticus is a common cause of UTIs in young women
6
Q
What is important about Staphylococcus epidermidis?
A
Staphylococcus epidermidis is adept at attaching to and growing on prosthetic devices
(normal inhabitant of skin, nose, and mouth of humans; less virulent than S. aureus)
7
Q
Staphylococcus aureus is a [Gram, shape, description, metabolic]
A
Gram-positive cocci that grows in grape-like structures and is a facultative anaerobe
8
Q
What is the most virulent of the staphylococci?
A
Staphylococcus aureus
9
Q
Which compounds determine the pathogenicity of Staphylococcus aureus?
A
- Toxic shock syndrome toxin 1 (TSST-1)
- Staphylococcal enterotoxins A-E, G-I
- Exfoliatin (exfoliative toxin)
- Alpha toxin (alpha-hemolysin)
- Panton-Valentine leukocidin (PVL)
- Coagulase
- Protein A
10
Q
Why is TSST-1 from Staphylococcus aureus relevant?
How does TSST-1 exert systemic effects?
What sort of antigen is TSST-1?
A
Cause of most cases of bacterial toxic shock syndrome
May be produced by staphylococci growing at an isolated site, reach the bloodstream, and cause systemic effects without bacteremia
Superantigen
11
Q
Why are Staphylococcal enterotoxins A-E and G-I relevant?
How do they exert their effects?
Why are they hard to kill?
A
Cause staphylococcal food poisoning and toxic shock syndrome
Superantigens
Act directly on neural receptors in upper GI tract, stimulating vomiting center in brain to cause vomiting 2-5 hrs after ingestion
Resistant to boiling for 30 minutes and digestive enzymes
12
Q
What condition does exfoliatin from Staphylococcus aureus cause?
How does it do that?
A
Scalded skin syndrome
Disrupts intercellular junctions in the skin, leading to splitting of epidermis between stratum spinosum and stratum granulosum
13
Q
What kind of toxin is alpha-toxin from Staphylococcus aureus?
What kind of factor alpha-toxin an example of?
A
Pore-forming toxin
(inserts into lipid bilayers of mammalian cells, forms pores, causes cell death and tissue destruction)
Hemolysin
(lyses RBCs when bacteria are grown on blood agar plates, thought to lyse other types of cells during infections or disrupt intercellular junctions in epithelial barriers)
14
Q
What kind of toxin is Panton-Valentine leukocidin from Staphylococcus aureus?
What sort of Staphylococcus aureus infection is it associated with?
How does it work?
What is the gene for PVL carried by?
A
Pore-forming toxin
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)
Contributes to cell lysis, causing severe necrotic infections associated w/ many CA-MRSA strains
Bacteriophage
15
Q
What is the function of coagulase from Staphylococcus aureus?
How does it work?
A
Helps create a mechanical barrier that blocks off neutrophils
- Binds to prothrombin to form a complex
- Complex initiates polymerization of fibrin to form a clot
- Fibrin contributes to fibrin capsule surrounding many abscesses
- Mechnical barrier prevents neutrophils from entering abscesses
16
Q
What is the function of Protein A from Staphylococcus aureus?
How does it work?
A
Prevents antibody-mediated immune clearance
Binds to Fc portion of IgG molecules
17
Q
What clinical diseases does Staphylococcus aureus cause?
A
- Joint and bone infections
- Endocarditis
- Toxic shock syndrome
- Staphylococcal food poisoning
- Scalded skin syndrome
- Skin and soft tissue infections
- Hospital-acquired infections (nosocomial)
18
Q
How does Staphylococcus aureus cause joint and bone infections?
A
Gains access to bloodstream and causes infections at distant sites such as joints (septic arthritis) and bones (osteomyelitis)
19
Q
How does Staphylococcus aureus cause endocarditis?
Why does this often lead to death?
Which population is this especially common in?
What are the clinical signs?
A
Staphylococcus aureus goes to the bloodstream and causes localized infection of valves of the heart
Bacteria form biofilms on heart valves and a very difficult to eradicate with antibiotics
IV drug users
Osler’s nodes, Janeway lesions, conjunctivital hemorrhages, heart murmurs
20
Q
What are the symptoms of toxic shock syndrome from Staphylococcus aureus?
What tends to occur upon resolution of toxic shock syndrome?
What is this illness most associated with?
What is this illness also associated with?
Are blood cultures positive or negative?
A
High fever, vomiting, diarrhea, sore throat, muscle pain, rash, hypotension or shock that can lead to organ failure
Desquamation of skin, especially digits
Most common cause: tampon use (strains that colonize vagina and produce TSST-1)
Wound infections (S. aureus enterotoxins or TSST-1 are the cause)
Blood cultures are negative
21
Q
Which toxin is the cause of food poisoning in Staphylococcus aureus?
Describe food poisoning due to Staphylococcus aureus
A
Enterotoxin
A self-limited episode of vomiting and diarrhea that begins 2-5 hrs after ingestion of food contaminated w/ enterotoxins
22
Q
Which toxin is the cause of scalded skin syndrome due to Staphylococcus aureus?
What is the main symptom?
Which age groups are primarily affected?
Describe the localization of the infection
A
Exfoliatin
Desquamation
Infants and children under 5 years old
Infection is usually localized, such as conjunctivitis, but exfoliatin reaches bloodstream and may cause exfoliation at remote sites
23
Q
What is the difference between a furuncle and a carbuncle?
A
Furuncles are boils, most of which begin with the blockage of hair follicle or sweat gland that subsequently becomes infected
Carbuncles are multiple abscesses formed after infection spreads from a furuncle
24
Q
What types of skin and soft tissue infections does Staphylococcus aureus cause?
A
- Furuncle and carbuncle
- Cellulitis (also folliculitis, other soft tissue infections)
25
Which two types of bacteria tend to cause skin infections?
Staphylococcus aureus, group A streptococci
26
What is a nosocomial infection?
An infection acquired after people are admitted to the hospital and have undergone procedures
27
Describe the diagnostic laboratory test findings for Staphylococcus aureus
* Easily culturable on blood agar plates and seen on Gram-stain of tissue specimens
* Colonies have a gold color
* Catalase positive
* Coagulase positive
28
How can you differentiate Staphylococcus aureus from streptococci using a lab test?
Staphylococcus aureus is catalase positive
Streptococci are catalase negative
29
How can you differentiate Staphylococcus aureus from Staphylococcus epidermidis and Staphylococcus saprophyticus on a lab test?
Staphylococcus aureus is coagulase positive
Staphylococcus epidermidis and Staphylococcus saprophyticus are coagulase negative
30
How is Staphylococcus aureus infection treated?
Why is treatment difficult?
Drainage of all collections of pus and antibiotics
Almost all isolates produce a beta-lactamase that degrades penicillin
Antistaphylococcal penicillins (methicillin, nafcillin, oxacillin) and cephalosporins are resistant to beta-lactamases but MRSA is resistant to the antistaphylococcal penicillins
VRSA is resistant to vancomycin
31
Why is MRSA resistant to antistaphylococcal penicillins?
MRSA contains a variant penicillin-binding protein called PBP2' encoded by the mecA gene that does not bind beta-lactam antibiotics
32
How can MRSA be prevented?
* Isolation of colonized or infected patients
* Meticulous hand-washing and glove-wearing by healthcare personnel
33
Enterococci are [Gram, shape]
Enterococci are Gram-positive cocci
34
Which species of Enterococci are medically important?
Which is more common?
Which is more resistant to antimicrobials?
Enterococcus faecalis and E. faecium
E. faecalis is more common
E. faecium is more resistant to antimicrobials
35
Where are E. faecalis and E. faecium normally found?
GI tract
36
Why are Enterococci of medical concern?
Enterococci have antibiotic resistance especially to vancomycin
37
What carries the gene for vancomycin resistance in enterococci?
What biochemical change does the vancomycin resistance gene cause?
How does this make enterococci resistant to vancomycin?
Carried by a transposon that is carried by a self-transferrable plasmid
Encodes side chains that allow for synthesis and substitution of D-Ala-D-lactate for D-Ala-D-Ala in the peptide side chains of peptidoglycan
Vancomycin cannot bind to D-Ala-D-lactate
38
Where are Enterococci infections commonly acquired?
Where in the body do Enterocci infections occur?
Hospital (nosocomial)
UTIs, wounds, biliary tract, intra-abdomen, blood (intravascular catheters, endocarditis)
39
Describe the treatment strategy for Enteroccoci
* Penicillin/ampicillin (usually w/ aminoglycosides)
* If resistant to penicillin/ampicillin, use vancomycin
* If resistant to vancomycin, use linezolid or daptomycin
40
Why are amigolycosides added to penicillin/ampicillin in the treatment of Enterococci?
Pencillin/ampicillin are bacteriostatic against Enterococci
When aminoglycosides are added, the combo is bacteriacidal
41
Why would you not want to overuse vancomycin?
Overuse of vancomycin predisposes to vancomycin-resistant Enterococci (VRE) colonization/infection
42
Who commonly transmits VRE from patient to patient?
How can VRE be prevented?
Healthcare workers
Hand washing and contact precautions, judicious use of vancomycin
43
What procedure is important to order after Streptococcus gallolyticus infection? Why?
Colonoscopy to rule out colon cancer
44
Which skin infection can be associated w/ coronary bypass surgery involving veins removed from the leg?
Which bacteria causes this?
Cellulitis
Streptococcus pyogenes
45
How are streptococci grouped?
By hemolysis
**Alpha hemolysis**: partial hemolysis, greenish tint
**Beta hemolysis**: complete hemolysis, clear color; Group A, Group B, Group D (Note: Group D usually has gamma hemolysis)
**Gamma hemolysis:** Group D; no hemolysis
46
List the relevant alpha-hemolytic streptococci
Viridans streptococci
Streptococcus pneumoniae
47
List the relevant beta-hemolytic streptococci
Group A: Streptococcus pyogenes
Group B: Streptococcus agalactiae
Group D: Streptococcus gallolyticus (usually gamma or alpha hemolytic)
48
What determines the groupings for beta-hemolytic streptococci?
Groupings (A, B, D) ar based on the carbohydrate antigens in the cell wall
49
Describe viridans streptococci
* Alpha-hemolytic
* Generally nongroupable (20+ species)
* Includes *S. mutans, S. sanguis, S. intermedius, S. anginosus*
50
Describe Streptococcus pneumoniae
(Hemolysis, growth, clinical significance)
* Alpha-hemolytic
* Grows as diplococii on gram-stained specimen
* Causes pneumonia, other respiratory tract infections
* Virulence factors
* Capsule: Prevents phagocytosis
* Pneumolysin: degrades hemoglobin to a green pigment
51
What is the most clinically relevant group B streptococcus?
(Hemolysis, clinical significance)
*Streptococcus agalactiae*
Beta-hemolytic
* Causes neonatal sepsis, meningitis
* Colonizes the vagina; passed to the newborn during delivery
* Women who are GBS (+) are treated with penicillin or vancomycin prior to delivery
52
What is the most clinically significant Group D streptococcus?
(Hemolysis, clinical significance)
Streptococcus Gallolyticus
Gamma-hemolytic
* Rarely causes infections
* Bloodstream infection caused by S. Gallolyticus is often associated with colon cancer
53
Describe the laboratory findings that would indicate *Streptococcus pyogenes*
[Gram, growth patern, hemolysis, catalase, titers]
* Gram (+)
* Grows in chains or pairs
* Beta-hemolysis (group A)
* Catalase (-)
* ASL-O antibody titers
54
Describe the appropriate course of treatment for a *Streptococcus pyogens* infection
* Penicillin = treatment of choice
* Most strains are sensitive
* If STSS
* Treat with penicillin + clindamycin (inhibits SPE production)
* Give IVIG: Contains aintbodies against toxins
* If necrotizing fasciitis
* Treat with penicillin + clindamycin (inhibits SPE production)
* Surgical debridement necessary
55
List the relevant toxins associated with *Streptococcus pyogenes*
* Streptolysin (SLO)
* M Protein
* Streptococcal pyogenic endotoxins (SPEs)
* Streptokinase
* C5a Peptidase
56
List the clinical diseases associated with *Streptococcus pyogenes*
* Streptococcal pharyngitis
* Scarlet Fever
* Streptococcal Toxic Shock Syndrome (STSS)
* Necrotizing fasciitis
* Impetigo
* Cellulitis
* Rheumatic Fever
* Post-streptococcal glomerulonephritis (PSGN)
57
Describe the mechanism of action of streptolysin (SLO)
Note: We generate antibodies to SLO; SLO antibodies are diagnostic of an *Streptococcus pyogenes* infection
SLO formes pores in the plasma membrane of human cells.
This transports virulence factors into the cell, leading to beta-hemolysis
58
List the clinical diseases associated with SLO toxin
Streptococcal pharyngitis
Post-streptococcal glomerulonephritis (PSGN)
59
Describe the relevant clinical findings for streptococcal pharyngitis
"Strep throat"
* Frequently occurs in children
* Sore throat
* Fever
* Headach
* Swollen, erythmatous tonsils, sometimes with purulent exudates
* Impossible to clinically differentiate from viral pharyngitis
* May be accompanied by scarlet fever
* Usually self-limiting (but routinely treated with antibiotics to reduce risk of rheumatic fever)
60
Describe the relevant clinical findings of post-streptococcal glomerulonephritis (PSGN)
* Onset 2 weeks after the initial S. pyrogenes infection
* Early treatment is does not prevent PSGN
* Damage due to accumulation of SLO antibodies/antigens in the kidney
* Can follow pharyngitis OR soft tissue infection
* Associated with edema, hypertension, hematuria, proteinuria
61
Describe the structure and significance of M protein
M protein is associated with streptococcus pyogenes infection
* M protein is made up of fibrillar molecules that extend past the bacterial surface
* It is anchored in peptidoglycan
* Used to serotype S. pyogenes
* **Prevents phagocytosis**
62
What clinical disease is associated with M protein?
M protein is the virulence factor associated with **_rheumatic fever_.** (Streptococcus pyogenes produces M protein)
63
Describe the cause of rheumatic fever
Onset ~3 weeks after onset of streptococcal _pharyngitis_
**M protein** is antiphagocytic and triggers a **humoral response**; _M_ protein **_m_**imicks **_m_**yosin in the heart, causing the body to mount a repsonse and **_attack myosin_**
This leads to permanent heart valve damage (_M_ protein leads to damage of the **_M_**itral valve)
**Early treatment of pharyngitis can prevent rheumatic fever**
64
How is rheumatic fever diagnosed?
Use JONES criteria
* J - Joints (polyarthritis)
* O - Heart problems (think of the O as a heart shape)
* N - Nodules (subcutaneous)
* E - Erythema marginatum (rash w/thick red border)
* S - Sydenham's chorea (rapid involuntary movements, especially in hands and face)
Look for SLO antibodies as evidence of a recent Group S streptococcus infection
65
Why is it important to treat streptococcal pharyngitis with antibiotics?
Early treatment can reduce the risk of developing rheumatic fever
66
Describe the effects of streptococcal pyogenic endotoxins (SPEs)
SPEA, SPEC -\> Scarlet Fever, STSS
SPEB -\> Necrotizing fasciitis
67
Which virulence factor is associated with necrotizing fasciitis?
SPE B
68
Describe the Streptococcal pyogenic endotoxins (SPEs)
SPEA, SPEC
* Superantigens
* Genes are carried by phage
* Only S. pyogene bacterium that are infected by a phage can produce SPEA and SPEC
* Lead to STSS, Scarlet Fever
SPEB
* Superantigen
* A protease
* Leads to necrotizing fasciitis
69
What are the causative virulence factors of scarlet fever?
SPEA, SPEC produced by streptococcus pyogenes infection
70
Describe the clinical findings associated with scarlet fever
* Streptococcus pyogenes infection
* Superantigens SPEA, SPEC
* Pharyngitis
* Erythmatous, sandpaper rash
* Widespread rash that spares the face/area around the mouth
* Accentuated in skin creases
* Strawberry tongue
71
Describe the clinical findings associated with Streptococcal Toxic Shock Syndrome (STSS)
Similar to TSS caused by staph infection
* Fever, hypotension, multi-organ failure
* No rash
* Not associated with tampon use
* Most patients are bacteremic, have an associated soft tissue infection
72
How would you differentiate between TSS and STSS?
TSS: Caused by *Staphylococcus aureus*
* Rash
* Associated with tampon use
STSS: Caused by *Streptococcus pyogenes*
* No rash
* Not associated with tampon use
73
Describe the clinical findings associated with necrotizing fasciitis
* *Streptococcus pyogenes* infection
* Protease: SPEB
* Necrossi of superficial and/or deep fascia of muscles
* Infection site is minor break in skin or surgical wound
* Abrupt onset
* Pain sensitivity, fever, malaise, with minimal physical findings
* Tissue damage progresses rapidly
* Buliae on surface
* Mottled, dusky skin over necrosis
74
What is streptokinase?
Why is it significant?
Streptokinase is virulence factor associated with streptococcus pyogenes
It causes lysis of fibrilin clots by converting plasminogen to plasmin
* Bad: causes bacteria to spread
* Good: Therapeutic uses in lysing coronary artery clots in acute myocardial infarction
75
Which streptococcus pyogenes-associated virulence factor has a therapeutic use?
Streptokinase; it is used to lyse coronary artery clots in acute myocardial infarction
76
What is C5a peptidase?
What does it do?
A virulence factor associated with S*treptococcus pyogenes*
It is an extracellular enzyme that cleaves C5a (a complement component)
- This prevents the recruitment of phagocytes to bacteria
77
Describe the clinical findings associated with impetigo
Infection by *Streptococcus Pyogenes*
* Infection of the epidermis
* Seen in children
* Associated with poor hygiene
* Small vescicles on exposed skin enlarge and become pustular
* Vescicles rupture -\> **yellow crust**
78
Describe the clinical findings associated with cellulitis
Infection by *Streptococcus Pyogenes*
* Infection of the dermis, subcutaneous tissue
* Fever, lymphangitis
* Located at sites wtih compromised lymph drainage
79
List the soft tissue infections associated with *Streptococcus pyogenes*
* Impetigo
* Cellulitis and Erysipelas
* Necrotizing fasciitis
80
List the nonsupprative sequale associated with *S**treptococcus pyogenes* infection
* Post-streptococcal glomerulonephritis
* Follows soft tissue infection of pharyngitis
* 2 weeks initial infection
* Early treatment of the initial infection cannot prevent
* Rheumatic fever
* Follows pharyngitis only
* 3 weeks after initial infection
* Early treatmetn of the initial infection can prevent
81
Straberry tongue is associated with [disease], caused by [bacteria]
Straberry tongue is associated with **scarlet fever**, caused by ***streptococcus pyogenes***
82
What condition is caused by streptococcal pyogenic enterotoxin B?
Necrotizing fasciitis
83
What bacteria causes impetigo and cellulitis?
*Staphylococcus aureus* or *streptococcus pyogenes*
84
Bacillus spp. are [metabolic, Gram stain, shape, important characteristc]
Bacillus spp. are aerobic Gram-positive rods that form spores
85
Which Bacillus bacteria are of medical importance?
* Bacillus anthracis (anthrax)
* Bacillus cereus (food-poisoning)
86
Bacillus anthracis is a [metabolic, Gram stain, shape, feature of growth, important characteristic]
Bacillus anthracis is aerobic Gram-positive rods that grows in chains (bamboo rods/box cars) and forms spores
87
How are humans exposed to Bacillus anthracis?
Who is most at risk?
Handling of contaminated meats and hides
Agricultural workers and veterinary personnel
88
Where are virulence factors for Bacillus anthracis carried?
Plasmids
89
What are the determinants of pathogenicity of Bacillus anthracis?
Where are they found?
* Anthrax toxin
* Capsule composed of poly-D-glutamic acid
Both found on a plasmid
90
What sort of toxin is anthrax toxin?
A-B toxin
91
How do A-B toxins work?
Fragment B (binding) binds to surface of cells and transports Fragment A into cells
Fragment A (active) has activity that damages cell
92
What kind of toxin is anthrax toxin?
Describe the structure of anthrax toxin
A-B toxin
Actually two toxins that share the same B subunit
B subunit: edeme factor and lethal factor
A subunit: protective antigen
93
How does the edema factor portion of the anthrax toxin exert its effects?
1. Has adenylate cyclase activity
2. Increases intracellular cAMP levels
3. Causes edema and inhibition of neutrophil phagocytosis
94
How does the lethal factor portion of anthrax toxin exerts its effects?
1. Zinc metalloprotease that cleaves host cell kinases
2. Causes lysis or inactivation of macrophages, dendritic cells, and suppressor T cells
95
What does protective antigen (PA) do?
Forms a pore that binds to cells and facilitates entry of edema factor and lethal factor
96
What is the capsule of Bacillus anthracis composed of?
Where is it encoded?
How does this protect Bacillus anthracis?
Poly-D-glutamic acid
Encoded on plasmid
Has antiphagocytic properties
97
What clinical diseases does Bacillus anthracis cause?
* Cutaneous anthrax
* Inhalation anthrax (Woolsorters' disease)
* Gastrointestinal anthrax
98
List the types of diseases caused by Bacillus anthracis in order of decreasing mortality
Inhalation anthrax \> GI anthrax \> cutaneous anthrax
99
How does cutaneous anthrax occur?
Describe the symptoms of cutaneous anthrax
How does cutaneous anthrax resolve?
Spores introduced into skin through cuts or abrasion exposed to contaminated carcasses or through fly bights
Small red papule enlarges to form an ulcer w/ blackened necrotic eschar surrounded by expanding zone of edema, painless, may be surrounded by small satellite vesicles
Spontaneously resolves
100
How does inhalation anthrax (Woolsorters' disease) occur?
Describe the symptoms of inhalation anthrax
What disease does inhalation anthrax resemble?
How does inhalation anthrax resolve?
Spores inhaled often during handling of contaminated hides, hair, or wool
Fever, shortness of breath, hypotension
Resembles the flu
Death
(large hemorrhagic mediastinal lymph nodes are common, organisms sometimes seen on blood smear)
101
What is a telltale symptom of inhalation anthrax on xray?
Widened mediastinum
102
How does gastrointestinal anthrax occur?
Describe the symptoms of gastrointestinal anthrax
Ingestion of contaminated meat
Ulcers form at site of infection (mouth, esophagus, intestine)
103
What diagnostic lab tests are used for Bacillus anthracis?
* Gram-staining
* Grow from pus, blood, or sputum streaked on blood agar plates
* Serologic tests
104
What is notable about Gram-staining of cutaneous lesions of someone with cutaneous anthrax?
Large number of Bacillus anthracis organisms will be seen
105
How is Bacillus anthracis treated?
* Sensitive to penicillin
* Ciprofloxacin and doxycycline are recommended due to concerns about weaponized strains resistant to penicillin
* Second agent added for inhalational anthrax (rifampin, vancomycin, pencillin, clarithromycin)
* Raxibacumab and oblitoxaximab for inhalational anthrax
106
How do raxibacumab and obiltoxaximab work?
Monoclonal antibodies that bind to host cell receptor of PA and prevent binding of PA to the receptor
107
How can anthrax infection be prevented?
* Nonliving vaccine (PA active component) used in humans
* Live-attenuated vaccine containing spores used in domestic animals
* 60 day course of ciprofloxacin recommended after presumed exposure to aerosolized spores
108
Listeria are [Gram stain, metabolic, shape]
Listeria are Gram-positive facultatively anaerobic rod-shaped bacteria
109
Which species of Listeria is medically important?
Listeria monocytogenes
110
Listeria monocytogenes are [Gram stain, metabolic, shape, intra/extracellular]
Listeria monocytogenes are Gram-positive facultatively anaerobic rod-shaped bacteria that are facultatively intracellular
111
At what temperatures do Listeria monocytogenes grow well in?
Refrigeration temperatures
112
What route of transmission is important for Listeria monocytogenes?
Foodborne transmission (unpasteurized milk, cheeses, coleslaw, raw meat)
113
Name a common case of Listeria monocytogenes infection
Person infected after eating at a delicatessen
114
What does it mean that Listeria monocyotgenes is a facultative intracellular pathogen?
Can grow and replicate in environment (not obligate intracellular)
Ability to invade eukaryotic cells is essential step in its pathogenesis
115
What are adhesins?
Factors that mediate adherence of bacteria to eukaryotic cells
116
What does internalin do for Listeria monocytogenes?
Mediates attachment and invasion of mammalian cells (a type of adhesin)
117
What happens when Listeria monocytogenes bacteria enter a cell?
1. Briefly reside inside intracellular vacuoles
2. Escape via listeriolysin O
3. Propel themselves around cytoplasm by forming and pushing against actin tails
4. Form protrusions into neighboring epithelial cells using ActA
5. Membranes around protrusions lysed
6. Bacteria enter cytoplasm of adjacent epithelial cells without exposure to external environment
118
What kind of toxin is listeriolysin O?
What other toxins is listeriolysin analogous to?
Pore-forming toxin
Analogous to streptolysin O of Streptococcus pyogenes and pneumolysin of Streptococcus pneumoniae
119
What bacterial protein does Listeria monocytogenes use to propel around the cytoplasm by forming and pushing against actin tails and then form protrusions to neighboring epithelial cells?
ActA
120
What is the purpose of protrusions formed by Listeria monocytogenes?
Protrusions allow Listeria monocytogenes to enter cytoplasm of adjacent epithelial cell without exposure to external environment or humoral immune system)
121
What clinical diseases does Listeria monocytogenes cause?
* Asymptomatic or influenza-like illness in pregnant women (but can cause abortion, premature delivery, bacteremia)
* Neonatal disease (early or late onset)
* Mengitis in elderly or immunocompromised individuals
122
How is early onset neonatal disease due to Listeria monocytogenes acquired?
What is it characterized by?
Transmission across placenta from infected mother
Disseminated abscesses and granulomas
123
What can late onset neonatal disease due to Listeria monocytogenes cause?
Meningitis
124
How is Listeria monocytogenes infection usually diagnosed in diagnostic lab tests?
What are the important characterisrtics?
* Growing organism from CSF, blood, amniotic fluid
* Small smooth colonies surrounded by narrow rim of beta-hemolysis when grown on blood agar plates
* Catalase positive
* Characteristic tumbling motility in fluid media at 25ºC
125
Listeria monocytogenes is [type of hemolysis, reaction to catalase, and type of motility]
Listeria monocytogenes is beta-hemolytic, catalase positive, and has tumbling motility
126
How is Listeria monocytogenes treated?
* Ampicillin (may be used in combo with aminoglycoside for synergy)
* Trimethoprim-sulfamethoxazole is bactericidal and recommended for those with penicillin allergies
127
How can Listeria monocytogenes infection be prevented?
* Avoiding raw meat and unpasteurized milk and cheese especially during pregnancy
* Washing raw vegetables
128
Cornyebacteria are [metabolic, Gram stain, shape, distinctive morphology]
Corynebacteria are aerobic Gram-positive bacilli that can have an irregular swelling (club shape) on one end under certain growth conditions
129
Which species of Corynebacteria is best known?
Corynebacteria diptheriae
130
Corynebacteria diptheriae is a [metabolic, Gram stain, shape, distinctive morphology]
Corynebacteria diptheriae are aerobic Gram-positive bacilli that can have an irregular swelling at one end (club shape) under certain growth conditions
131
What is disease does Corynebacteria diptheriae cause?
Diphtheria
132
How is Corynebacteria diptheriae maintained in humans?
What are the hosts for Corynebacteria diptheriae?
Asymptomatic carriage in immune humans
Humans are the only host
133
How is Corynebacteria diptheriae transmitted from person to person?
Direct contact or droplets
134
What is the determinant of pathogenicity of Corynebacteria diptheriae?
Diphtheria toxin
135
What type of toxin is diphtheria toxin?
What carries diphtheria toxin?
Both A-B toxin and ADP-ribosylating toxin
Carried on integrated bacteriophage
136
How does Diphtheria toxin work as an A-B toxin and ADP-ribosylating toxin?
1. Fragment A inhibits peptide chain elongation during protein translation by ADP-ribosylating EF-2
2. Inhibits protein synthesis in pharyngeal epithelial cells, leading to necrosis
137
What is an ADP-ribosylating toxin?
Toxin that transfers ADP-rubose from NAD to host cell proteins, altering the activity of these proteins
138
List examples of ADP-ribosylating toxins
* Diphtheria toxin of Corynebacteria diptheriae
* Exotoxin A of Pseudomonas aeruginosa
* Cholera toxin of Vibrio cholerae
* Heat labile toxin of Escherichia coli
* Pertussis toxin of Bordetella pertussis
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Describe the clinical disease caused by Corynebacteria diptheriae
* Usually affects kids
* Sore throat, fever, difficulty swallowing, cough, hoarseness, rhinorrhea
* Thick grey adherent pseudomembrane on mucosa of the oropharynx, palate, nasopharynx, nose, or larynx that may lead to airway obstruction
* Damage to heart causing cardiac arrhythmias
* Nerve damage causing paralysis of eye muscles, soft palate, extremities
* Adrenal damage causing hypoadrenalism
* Skin infections
140
What is a prominent indicator of diphtheria?
Thick grey adherent pseudomembrane observed on mucosa of oropharynx, palate, nasopharynx, nose, or larynx
(composed of necrotic cell debris, fibrin, and blood cells that accumulate after cell damage caused by diphtheria toxin)
141
How is Corynebacteria diptheriae diagnosed on lab test?
* Gram stain of smears: bacteria lie in clusters at acute angles (Chinese letter) or parallel groups (palisade)
* Gray to black colony on specialized medium containing tellurite that inhibits growth of most upper respiratory bacteria
142
What is notable about definitive laboratory tests for Corynebacteria diptheriae?
Require at least a week
143
How is Corynebacteria diptheriae treated?
* Horse antisera against diphtheria toxin
* Patients monitored for respiratory or cardiac failure
* Antibiotics given to prevent spread of infection, not to increase rate of healing in people who have receive antitoxin (macrolides, penicillin G, rifampicin, clindamycin)
* Close contacts should be cultured and given vaccination booster if required
144
Why are antibiotics used in people who have received the antitoxin for diphtheria toxin?
To prevent spread of the infection
Do not increase rate of healing in people who have received antitoxin
145
How can Corynebacteria diptheriae be prevented?
A diphtheria toxin toxoid vaccine (produced after DT treated with formaldehyde)
146
What is a toxoid?
A chemically treated toxin that is no longer toxic but retains immunogenicity
147
Why can individuals vaccinated with the diphtheria toxin toxoid vaccine still spread disease to unvaccinated individuals?
Vaccinated individuals are protected from disease but can be colonized by Corynebacteria diptheriae
148
What caracteristics **initially** distinguish necrotizing fascitis from other skin infections?
- Very painful upon palpation
- Dark spots indicating air in deep fascia/muscle upon CT scan
- Rash itself might not look too bad on the surface of the skin
149
Why does necrotizing fasciitis spread so quickly?
SPE B breaks down tissue quickly, causing the necrotizing fasciitis to spread.
150
How would you treat a furuncle?
Incision and Drainage
May follow with antibiotics
151
If you don't see any pus, which organism is likely causing an erythmatous skin legion?
Strep spp (especially S. pyogenes)
152
What organism usually causes an infection where a pus-filled abscess or furuncle is present?
Staphylococcus spp.
(Especially S. aureus)
Staph is coagulase (+). Coagulase converts fibrinogen to fibrin, which forms a barrier around the furuncle
153
How would you treat necrotizing fasciitis?
Surgical debridement
IV antibiotics (Penicillin + Clindamycin)
Note: Penicillin acts on cell wall, clindamycin inhibits SPE production
Most Strep spp are penicillin sensitive; If S. aureus is causing abscess, be aware of MRSA
154
A 36-week pregnant woman comes into your outpaitent OB/Gyn office. Your preceptor orders a vaginal swab
Why?
What do you do if she tests positive?
Screen for Group B strep, caused by *Strep**. agalactiae*
If she tests positive, administer intrapartum antibiotics (penicillin = first choice; ampicillin also works)
155
What bacterium has this appearance when grown on tellurite agar?
Corynebacterium Diphtheriae
156
Which gram-positive bacteria have available vaccines?
* *Corynebacterium diphtheriae*
* *Bacillus anthraces*
* *Clostridium tetani*
157
Which bacteria is this?
*Bacillus anthracis*
Gram (+), rod-shaped bacteria that grows in chains
158
Which bacteria have a capsule made from Poly-D-glutamic acid?
*Bacillus Anthracis*
159
Growth of this pseudomembrane in the oropharynx is associated with which bacteria?
*Corynebacterium diphtheriae*; seen in diphtheria patients
160
*Clostridium tetani* is a [Gram stain, metabolic, shape distinctive morphology]
*Clostridium tetani* is a gram (+), obligate anaerobe bacillus that forms terminal spores that exist in large reservoirs in soil
161
What are the 4 medically relevant clostridia spp?
* C. tetani*
* C. botulinum*
* C. perfringens*
* C. difficile*
162
What clinical disease is associated with *Clostridium tetani?*
Tetanus
163
Which organism forms these spores?
*Clostridium tetani*
Forms _terminal_ spores - club/drumstick shaped
reservoir in soil
164
What kind of toxin is tetanus toxin?
A-B Toxin
165
Describe the structure and action of tetanus toxin
Tetanus toxin is an A-B toxin
* Synthesized as a single polypeptide chain, which is cleaved and linked via disulfide bonds
* B = heavy chain
* A = light chain
* A protease that cleaves SNARE proteins in neuronal synapses
* Acts on **Renshaw** cells to inhibit the release of **GABA and glycine**
* This decreases inhibitory signaling, resulting in rapid firing of motor neurons, leading to rigidity/increased tone
166
What cells does tetanus toxin act on?
What is the result?
Tetanus toxin acts on Renshaw cells (inhibitory neurons in the CNS) to **prevent the release of GABA and glycine**
The result is loss of inhibitory signaling -\> rapid firing of motor neurons -\> increased muscle tone
167
What kind of wounds may become infected with *Clostridium tetani*?
Deep puncture wounds
The bacteria is an obligate anaerobe; the spores must reach a part of the body where the is no oxygen in order to germinate
168
Describe the transport of tetanus toxin in the body
Retrograde transport from the site of inocculation to the neuron cell bodies in the CNS
169
Describe the clinical manifestation of tetanus
* Rigidity in...
* Jaw (lockjaw)
* Neck, shoulder, back (opisthotonus)
* Abdominal and leg muscles
* Spasms caused by minor stimuli
* Sympathetic nervous system involvement
* Hypotension
* Tachycardia
* Arrhythmia
* Sweating
* Vasoconstriction
170
How is Tetanus diagnosed?
Consistent clinical findings
Tetanus toxin production
Note: Isolating spores is not indicative of disease; sometimes healthy people have spores, sometimes diseased people do not
171
How is tetanus treated?
* Penicillin or metronidazole (**but antibiotics in general have unproven value**)
* Human tetanus immunoglobulin: Neutralizes unbound tetanus toxin
* Other agents to control muscle spasm
172
How can tetanus infection be prevented?
Vaccine of tetanus toxoid
Boosters to follow trauma
173
This baby cannot relax their face.
What is this called?
What is most likely causing this condition?
What else would you look for to confirm your diagnosis?
How would you treat it?
This face is characteristic of lockjaw, also called **risus sardonicus**
It is most likely caused by *Clostridium tetani* infection
Also look for arching of the back, increased muscle tone in other muscles. Inquire about puncture wounds (more relevant in adults maybe)
It should be treated with penicillin or metronidaole, as well as human tetanus immunoglobulin to neutralize the unbound toxin
174
*Clostridium botulinum* is a [Gram stain, metabolic, shape, distinctive morphology]
Clostridium botulinum is a Gram (+) obligate anaerobe bacillus that forms subterminal spores. It is found is soil, ponds, lakes, and on plants
175
Where are *C**lostridium tetani* spores in the environment found?
Soil, rusty nails (construction sites)
176
What disease is caused by *Clostridium botulinum*?
Botulism (Food borne, wound, or infant)
177
Which organism forms these spores?
*Clostridium botulinum*
Forms _Subterminal_ spores
178
What is the difference between tetanus toxin and botulism toxin?
Their targets;
Tetanus toxin targets **inhibitory neurons** in the CNS (renshaw cells), inhibiting **GABA and glycine** release
Botulinum toxin targets **motor neurons** in the CNS, inhibiting **ACh** release
179
What are the three diseases caused by *C. botulinum*?
Food-borne botulism
Wound botulism
Infant botulism
180
What bacteria causes "floppy baby syndrome"
*Clostridium botulinum*
181
Describe the structure and action of botulinum toxin
Botulinum toxin is an **A-B toxin**
* B = Heavy chain
* A = Light Chain
* Protease
* Cleaves SNARE proteins in **motor neurons**, inhibiting the release of **ACh**
* This results in inhibition; **muscles cannot contract, causing _flaccid paralysis_**
182
Where are people likely to contract food-borne botulism?
Canned foods; the spores germinate in the anaerobic environment of the can
Humans ingest the pre-formed toxin (toxin can survive boiling for 10+ minutes)
183
Describe the clinical manifestation of food-borne botulism
Symmetric **descending, flaccid** paralysis
* Diplopia, ptosis (droopy eyelids)
* Dysarthria
* Dysphagia
* Respiratory failure
* Nausea, vomiting, abdominal pain (fever unusua)
* Look for groups presenting together (families, people who live together, anyone who may have eaten the same food)
184
Describe the clinical manifestation of wound botulism
A wound contaminated by *Clostridium botulinum* spores
Symptoms same as food borne but no GI symptoms
* Symmetric descending flaccid paralysis
* Diplopia, ptosis
* Dysarthria
* Dysphagia
* Respiratory failure
185
Why is it recommended that children \<12 months old do not consume honey?
Honey has a large concentration of *Clostridium Botulinum* spores
Unlike adults, these **spores can germinate in the infant intestine**, due to lack of natural flora
This predisposes infants to botulism from spore ingestion
186
How is infant botulism different from food-borne botulism?
Infant botulism: ngestion of **spores**
Food-borne botulism: ingestion of the **pre-formed toxin**
Spores cannot germinate in the adult intestine, but they can germinate in the infant's; this leads to toxin production and infant botulism
187
Why dont *Clostridium botulinum* spores germinate in the adult intestine?
Natural flora prevents germination (and thus prevents botulinum toxin production)
188
How is botulism diagnosed?
* Compatible history and clinical symptoms (descending flaccid paralysis)
* Isolation of the toxin or organis from vomit, stool, or wound
* May be found in blood
189
How is botulism treated?
* Respiratory support
* Trivalent equine antitoxin
* Antibiotics to eliminate residual toxin are unproven
190
How is botulism prevented?
No vaccine is available
Thoroughly cook canned foods/practice proper canning techniques
Don't feed honey to infants \<12 months
191
What are the major differences between botulism and tetanus infetions?
Type of paralysis
* Tetanus = increased muscle tone
* Botulism = no muscle tone
Method of contracting the disease
* Tetanus = puncture wound
* Botulism = canned food, wound, honey (infant)
Treatment
* Tetanus = Human tetanus immunoglobulin, penicillin or metronidazole
* Botulism = Trivalent equine antitoxin, respiratory support
192
What are the major differences between *Clostridium tetani* and *Clostridium botulinum?*
Site of action
* *C. tetani:* Renshaw cells (inhibitory neurons in CNS)
* *C. botulinum:* Motor neurons
Spore formation
* *C. tetani:* Terminal spores
* *C. botulinum:* Subterminal spores
Where it's found
* *C. tetani:* Soil, construction sites (rusty nails)
* *C. botulinum:* Canned foods (found in soil, ponds, lakes, on plants, but adult humans only contract disease from pre-formed toxin, found typically in canned foods)
193
What are the medically-important families of actinomycetes?
*Nocardia* spp.
## Footnote
*Acinomyces israelii*
194
What is unique about the growth of Actinomycetes bacteria?
They are true growing bacteria, but from long, branchin filaments that resemble fungi
195
This is a kinyoun stain of which bacteria?
Nocardia
Grows in long, branching filaments; stains partially acid fast
196
Nocardia spp. are [Gram stain, metabolic, shape distinctive morphology]
Nocardia spp. are gram (+) obligate aerobes. They grow in long, branching filamentous rods with cells that remain conjoined after division
Catalase (+), Does **not** form spores,
197
What is the main determinant of pathogenicity for *Clostridium tetani?*
Tetanus toxin
198
What is the main determinant of pathogenicity for *Clostridium botulinum*
Botulinum Toxin
199
What is the main determinant of pathogenicity for *Nocardia?*
It cannot be killed efficiently by neutrophils
* Neutralizes oxidants
* Prevents phagosome acidification
* Inhibits phagosome-lysosome fusion
This means that cell-mediated immunity is needed to control the infection
200
Which individuals are most likely to be infected with *Nocardia?*
Anyone with **deficient cell-mediated immunity.** This includes patients with...
* Lymphoma
* Transplants
* Glucocorticoid use
* Men (more sucesptible than women
201
What are the 3 diseases caused by *Nocardia?*
Pulmonary nocardiosis
CNS nocardiosis
Transcutaneous nocardiosis
202
Describe the clinical presentation of pulmonary nocardiosis
* Subacute pneumonia
* Forms nodules, cavitary lesions, abscesses
* Ignores tissue planes
* Empyma (pus in pleural space)
* May disseminate to systemic circulation
* Causes **CNS nocardiosis** w/brain abscesses
203
Describe the clinical presentation of CNS nocardiosis
Brain abscesses
Preceded by pulmonary nocardiosis
204
Describe the clinical presentation of transcutaneous nocardiosis
* Inoculation of an open wound with *nocardia* spp
* Usually foot tissue after local trauma associated with walking barefoot
* Seen more often in developing countries
* Induration (hardened mass) and inflammatory reaction
* May forma a fistula with serous or purulent discharge
* Spreads slowly
* Ignores tissue planes
* May involve skin, subcutaneous tissue, bone
* May take years to spread
205
How is a *Nocardia* infection diagnosed?
* The organism is present in large numbers in lesions
* Truly gram (+)
* Stains partially acid-fast on Kinyoun or Carbol Fuchsin
* Catalase (+)
* Urease (+)
* Organisms are culturalbe on blood agar
* Grows as characteristic filamenous structures
* **But may take 2 weeks for colonies to be visible**
206
How is a *Nocardia* infection treated?
Choice: Trimethoprim/sulfamethoxazole
Alternative: Minocycline, amikacin
Brain abscesses may need to be drained, debridement may be necessary
207
How can *Nocardia* infection be prevented?
It can't really... No vaccine is available
208
*Acinomyces israelli* is a [Gram stain, metabolic, shape distinctive morphology]
*Actinomyces israelii* is a **gram (+)**, obligate **anaerobe** that grows in **filamentous rods** that resemble fungus
It is part of the normal flora of the mouth, GI tract, and female genital tract
209
What are the major differences between *Nocardia* spp. and *Actinomyces israelii?*
Metabolism
* *Nocardia* = obligate aerobe
* *A. israelii* = obligate anaerobe
Staining
* *Nocardia* stains partially acid fast
* *A. israelii* does not
210
What disesaes are caused by *Actinomyces israelii?*
Indolent, supprative infections
* Indolent = painless
* Supprative = pus-forming
Examples
* Oral-cervicofacial actinomyces infection
* Pulmonary/chest infection
* Abdominal/pelvic infection
211
How do people typically contract an *Actinomyces israelii* infection?
Usually through a jaw trauma or tissue injury that causes *A. israelii* to grow in a place where it doesn't usually grow
Examples: Dental work or other injury
212
Describe the clinical presentation of an oral-cervicofacial actinomyces infection
Slow!
* Begins as a nontender lump
* Turns into an abscess
* Forms draning sinus tracts containing pus with **yellow sulfur granules**
213
Describe the clinical presentation of a pulmonary/chest infection caused by *Actinomyces israelii*
Occurs if infectious contents in the mouth are aspirated
* Infection fo pulmonary parenchyma and pleural space
* May spread to involve bone and chest wall
214
What might trigger an abdominal or pelvic infection of *A. israelii?*
Intestinal rupture or IUD use
215
How is an *Actinomyces israelii* infection diagnosed?
Organism seen in gram-stained sulfur granules
* The granules themselves are diagnostic of *Actinomyces israelii* infection
* The organism will grow from cultures
* **If sulfur granules are not present, it may just be part of normal flora**
* Not acid fast (distinguishes from *Nocardia*)
216
How is an *Actinomyces israelii* infection treated?
Choice: Penicillin
Alternative: Tetracycline
May need surgical drainage in complicated cases
217
Describe Clostridioides difficile
[Gram stain, metabolism, shape]
Clostridioides difficile, aka C. diff is a **gram-positive, anaerobic bacillus**
Note: Spore forming, like other C*lostridioides* spp.
218
What is the clinical manifestation of a *C. difficile* infection?
Diarrhea due to inflammation caused by toxigenic strains that disrupt the epithelial barrier of the large intestine, causing fluid leakage. Usually watery, may be bloody
* Caused by **antibiotic use** that wipes out the normal flora of the gut or **ingestion of C. diff spores**
219
Which bacterial infection is associated with antibiotic use?
C. difficile
