Exam 2 Flashcards
Chlamydia
Small
Gram Negative
No peptidoglycan in cell wall
Chlamdydia is what type of bacteria
Obligate intracellular bacteria
Rely on host for amino acids
Biphasic life cycle of Chlamydia
Elementary bodies
Reticulate bodies
Elementary bodies of chlamydia
Smaller rigid cell wall
*Infectious form
Extracellular survival
Reticulate bodies of chlamydia
Larger fragile metabolically active
Intracellular growth
*Replicative form
Retic=replicative
Different biovars of chlamydia trachoma this have different
Tropisms and cause different diseases
Respiratory, urgoentifcal, colorectal, conjunctiva etc.
Life cycle of C. Trachomatis
Attachment and enter of elementary body to target cells
Attaches and induces endocytosis (TARP)
Formation of Reticulate body
-using stored ATP and EB converts to replica time RB
Binary fission of Reticulate bodies
-inhibits Lysomal fusion in host cell
—forms its own membrane bound vehicle…inclusion where replication takes place
Once a threshold of RBs is reached they convert back to EB
TARP
Translocated actin recruiting protein
CPAF
Chlamydia pro teases like activity factor
-regulates cellular apoptosis signals
C. Trachomatis Epidemiology
Humans are the sole reservoir
Disease in conjunctiva or genital tract
Most common bacterial STI worldwide
Neonatal conjunctivitis
What is a common cause of neonatal conjunctivitus
C. Trachomatis
Contact with infected cervical secretions—vaginal delivery
Chronic follicular conjunctivitis
7-9 million people
Usually contracted in infancy or early childhood from mother or close contacts
Spreads directly by contact with infected secretions
- fomites
- fingers
- flies
Chlamydia urethral infections
5% general population
Very contagions
Asymptotic infection in men
2-6 week incubation period **
Chlamydiae Tissue Tropism
Columnar epithelial cells of the endocervix and upper genital tract of women and the
- urethra
- rectum
- conjunctiva of both sexes
Other tissue tropism of chlamydiae
Depending on biovar other cell types can also be infected
Endothelium
Smooth Muscle
Lymphocytes
Macrophages
MOMP
Initial attachment mediated by MOMP
Major outer membrane protein followed by endocytosis
LGV biovars
Can also enter through breaks in skin or mucosa
Once replciative cycle of chlamydia is established primary injury is due to
Inflammation
IL-8 released by infected epithelial cells
Leads to early tissue invasion by PMN followed by lymphocytes macrophages plasma cells and eosinophils
Chlamydiae LPS
Likely also contributes to inflammation
Failure of immune system to control chlamydia infection
Aggregate of lymphocytes and macrophages form in submucosa- leading to necrosis; fibrosis and scarring
Chlamydia fibrosis and scaring results in
Infertility in female
Blindness in the eye
Immunity to Chlamydia
Immunity takes a long time to develop and is incomplete
Th1r Response (chlamydia)
Cd4+ TCell response
TH2 direct at MOMP May participate but antibody is associated with injury in chronic forms of the disease trachoma
Chlamydia Trachoma
Chronic inflammation of eyelids can lead to scarring of cornea
- usually seen in less developed countries
- Often lead to blindness
Inclusion conjunctivitis (Chlamydia)
Acute infection presents in newborns as mucopurulent eye discharge
Mother—>infant
Not associated with chonociity or blindness
Can lead to infant pneumonia syndrome
Genial Infections Chlamydia trachomatis
Men
Similar to N. Gonorrhoeae
Urethritis and epididymitis in men
Genial Infections Chlamydia trachomatis
Women
Cervicitis
Salpingitits
Urethral syndrome
Can lead to pelvic inflammatory disease
Lymphogranuloma Venereum
LGV
Caused by invasion biovars L1 L2 L3
Entry: through break in skins, transient genital lesion
Results in swollen glands in groins
Can also cause hemorrhagic ulcerative proctitis
Nucelic Acid amplification test
Used to detect chlamydia and N gonorrhoeae DNA
Rapid specific sensitive
C trachomatis treatment
Azithromycin
Doxycycline for LGV
Rickettsiae
Small
Gram negative
Nonmotile
Rickettsiae type of parasite
Obligate intracellular parasites
Reickttsiae cell envelope
LPS and two other large abundant outer membrane protein
Cell wall made of peptidoglycan
Reickttsiae Replcaition and Growth
Obligate intracellular parasite
Reductive evolution lead to loss of many core metabolic capabilities dependence on host
-requires host co-factors, amino acids, Phosphorylation sugars and ATP
Metabolize host derived glutamate vine aerobic respiration and TCA cycle
Slow growing dividing by binary fission in host cytoplasm or nucleus
Reickttsiae enter host cell through
Endocytosis attachment of OMP to many cell types
- induces phagocytosis
- escape phagosome using phospholipase
- grows freely in host cell cytoplasm
Reickttsiae transmitted via
Salivary gland of infected ticks or other vectors
Bacteria spread locally creating necrotic Escher (black sore)
Tropism for vascular endothelium multiplying in endothelial cells lining small blood vessels
Results in :
-Vasculitis
-Vascular lesions-> hypovolemia and hypotension
Reickttsiae causes thrombosis
Caused by focal areas of endothelial proliferation and perivascular infiltration
Leakage of red blood cells leads to rash and petechial lesions
Reickttsiosis two categories
Spotted Fever Group
Typhus group
Both characterized by fever, headache, myalgia and rash
Both can be fatal due to severe vascular collapse
Spotted Fever Group (SFG)
Most common in US
Rocky Mountain spotted fever
Rocky Mountain spotted fever caused by
rickettsia rickettsii
Primarily a parasite of ticks
Western States-Wood Tick
Eastern States-Dog ticks
Southwest and Midwest-lone star tick
Ubiquitous-brown dog ticks
Adult Female Ticks
Transmit the disease
Need blood meal to lay eggs
Adult ticks can survive up to 4 years without blood meal
RMSF Clinical Aspects
6-7 days after bite
Fever Headache Rash Toxicity Mental confusion Myalgia
RMSF Complication
Can lead to death
Blood clots (intravscualr coagulations)
Low platelets (thrombocytopenia)
Encephalitis (brain inflammation)
Vascular Collapse
Renal and heart failure
Rickettsia diagnosis
Serological diagnosis
rickettsia Treatmnet
Doxycycline
Sulfonamides
Typhus Group
More common in Europe
Causes three different Diseases
Epidemic Typhus Fever
R. Prowazekki, spread by body lice
(Not typhoid fever)
Only epidemic rickettsial disease
Endemic Typhus
R. Typhi
Spread by rat fleas
Scrub Typhus
Orienting tsutsugmaushi
Spread by chiggers
Typhus Fever pathogenesis
Human body louse gets infected during feeding
R. Prowazekii are present in lice poop 5 to 10 days after infection
Louse poop while they feed
- bacteria enters bloodstream when human scratches bite
- Louse feces are also infectious through mucous membranes of eyes and respiratory tract
Epidemic Typhus Symptoms
Incubation period is 1-2 weeks
Rash starts on trunk
Headache
Malaise
Myalgia
Epidemic Typhus Diagnosis
Serology is used to confirm but clinical history is used to justify treatment
Epidemic typhus treatment
Treatment must be started immediately to prevent complications
Doxycycline
Epidemic Typhus Prevention
Louse control is best means of prevention
No vaccine available
Endemic Murine Typhus
Resembles typhus but less severe
R. Typhi
Transmitted by rat Flea
Scrub typhus
Orient is tsutsugamushi
transmitted by rodent mite larvae—Chiggers
Necrotic Escher at bite
Scrub Typhus Symtpoms
Fever slowly increases
Maculopapular rash
Treatment: Docycycline
Bartonella
Closely related to Brucella
Gram Neg
Coccobacili
Facultative Intracellular Parasites
Bartonella Primary niche
Endothelial cells
Released into blood stream
Bartonella infects
Erythrocytes
Multiply and persist until taken up by arthropod
bartonella Vectors
Ticks Fleas Sand flies Mosquitos -Can cause co infections with Lyme disease
Bartonella henselae
Cat scratch Disease
Cat Scratch Disease
25,000 per year
Spread by cats scratch, bite, or cat fleas
Flea control can prevent. Cats are carriers
Swollen lymph nodes Skin rash Conjunctivitis Encephalitis Prolonged fever
Bartonella Quintana
Trench Fever
Trench Fever
Affects homeless alcoholic men
Spread by body louse
Sudden onset of chills
Headache
Relapsing fever
Maculopualr rash
Arthropod Disease Summary
B henselae
B Quintana
R typhi
R proqazekii
R rickettsii
Spirochete medically important genera
Treponema
Leptopira
Borrelia
Spirochetes
Loose Coils to rigid corkscrew
Rotation and flexion for movement
Spirochetes wall and membrane
Flexible peptidogluycan cell wall surrounded by axial fibrils
Outer bi-layered membrane (similar to gram neg)
ANUG
Acute necrotizing ulcerative gingivitis
Trench Mouth (ANUG)
Opportunistic infection
- severe malnutrition
- neglect of basic hygiene
- immunocompromised
Trench mouth symptoms
Bleeding gums Bad breath Metallic taste Sudden onset Unbearably painful
Treponema pallidum
Highly Motile
Corkscrew shaped
No LPS
Easily killed-drying, heat, detergents, and disinfectants
Treponema pallidum causes
Syphilis
T Pallidum relies on
Host for basic nutrients and metabolites
-Minimalist pathogen
Lacks energy generation pathways-no TCA or Electron Transport Chain
Slow growing and no enzymes
Syphilis epidemiology
Exclusively human pathogen
Primary or secondary lesion
Tertiary syphilis is not contagious
Spirochetes reach ____ tissues
Subepithelial
Entry unapparetn breaks in the skin or through mucous membrane
Multiplies slowly in the submucosa
Spreads to bloodstream
Primary lesion is an endarteritis T pallidum
Inflammation of inner lining of an artery and a necrotic ulceration later forms
Primary Syphillis
3 to 90 days after exposure
Primary lesion (chancre) appears at point of contact
Secondary syphilis
Occurs in about 1/3 of patients
Commonly involve skin mucous membranes and lymph nodes
Symmetrical reddish pink non itchy rash palms and soles
Latent Syphilis
Following secondary syphilis
No clinical symptoms
Occasional secondary replace can occur
Transmission to fetus is possibly during latency
Tertiary Syphilis
Untreated secondary syphilis develops into tertiary
Can manifest in numerous ways-nervous system and cardiovascular system are the worst
Neurosyphilis
Invasion of nervous system headache altered behavior loss of coordination paralysis tabes dorsal is sensory deficits and dementia
Ocular syphilis
Can involve almost any eye structure vision changes decreased visual acuity and permanent blindness
Cardiovascular syphilis
Aortiits leading to aneurysms
Gumma
Localized granulmaotus reaction to t pallidum
May be found in skin bone joints or other organs
Borrelia burgdorferi
Long slender spirochetes
Causes Lyme’s disease
Borrelia burgdorferi membrane
Outer membrane lacks LPS
Borrelia burgdorferi multiple classes of OMPs
Undergo antigenic variation referred to as outer surface proteins
OspA and AspC differentials expressed deepening on state of tick or mammalian infection
Lyme Disease primary reservoir
Rodents are primary
-tick larvae feed on mice and acquire Borrelia burgdorferi
Lyme disease is mainly contracted in spring or summer
Enzootic cylce of Borrelia burgdorferi
Two years and involves 3 blood meals
Larvae hatch from uninflected eggs
Feed on infected animal host acquire Borrelia burgdorferi
After a period of dormancy infected larvae molt into nymphs, which feed and transmit Borrelia burgdorferi to vertebrate host
Nymphs molt into adults which feed on an animal and mate
Only found where deer are present
Primary Lyme Diseae
Symptoms can begin within the first month after tick bite
Bull’s eye pattern-macula or pauper rash appears at bit site
Fever fatigue myalgia headache joints pions and mild neck stiffness
Lyme disease secondary
Secondary stage may develop days to months after primary rash- nervous system and CA system involvement
Fluctuating meningitis, cranial nerve palsies
AV block
Joint arthritis
Chronic lymes diseases
Treatment of Borrelia burgdorferi
Doxycycline and B lactams
Response to antibiotics is slow
Legionella pneumophila
Gram negative
Aerobic
Small bacilli
Water our and found in soil
Facultative intracellular bacteria
Legionella pneumophila type of pathogen
Opportunistic pathogen-only affects smokers and immunocompromised hosts impaired in cell mediated immunity
Facultative intracellular bacteria-requires special media to isolate
Legionella pneumophila causes
Atypical pneumonia
Legionella pneumophila virulence factors
Pili Flagella LPS Type IV secretion systems Legionella contains vacuole Low metabolic state
Legionella pathogenesis
Facultative intracellular bacteria
-can multiply inside free living amoebas other Protozoa and alveolar macrophages
Legionella Infection
Infection starts when aerosolized droplets of contaiminated water are breathed in to the lungs
Begins growing in macrophages causing inflammation producing necrotizing multifocal pneumonia
Legionella Containing Vaculoue
Effector proteins interfere with cell trafficking
-once inside bacteria surround themselves in a membrane bound vacuole-fusion with lysosomes is blocked
Intracellular multiplication of Legionella pneumophila
Is key to l pneumophila virulence
Innate and adaptive mechanisms are important to clear the infection and slow down bacterial replication
_____ in ____ and dendritic cells recognize legionella LPS
TLRs
Macrophages
TH1 adaptive immune response
INF-gamma IL2 and IL18 are produced and activated macrophages and intracellular killing of legionella
-cell mediated immunity is important
Legionellosis are linked to
Large complex man made water systems found in:
Hotels
Hospitals
Nursing Homes
Cruise ships
Two forms of legionellosis
Legionnnaries disease
Pontiac Fever
Both spread by contaminated water droplets
Legionannaires Disease
Severe form of the disease pneumonia
Pontiac Fever
Milder self limited form of disease with flu like symptoms
No pneumonia
Can also spread by exposure to contaminated soil
Symptoms of Legionnaires Disease
Starts with myalgia and headache
rapidly rising high fever
Dry cough on second or third day and chest pain
Chills vomiting diarrhea confusion and delirium
Hepatic dysfunction also common
Diagnosis of Legionella pneumophila
Direct fluorescent antibody with culture
Gram stain fails
Can be cultured on special media
Legionella pneumophila Treatment
Fluoroquinolong or azithromycin are current preferred treatments
Erythromcyin
penciling doesn’t work-produce beta lactamases
Prevention of Legionnaires
Minimize aerosols in public places from contaminated water
Prevention is complicated by legionella bacteria are relatively resistant to chlorine and heat so hard to prevent contamination
-forms biofilm
Zoonoses
Infections in humans acquired by direct or indirect contact with animals
Coxiella burnetii
Q fever
-inhalation of soil or dust contaminated with after birth or infect animals
Yersina pestis
Bubonic plaque
Exposure to fleas from infected rodents
Brucella
Undulant fever
Direct contact with infected animals
Ingested of contaimnated dairy products
Fancisella
Tularemia
Direct contact with infected mammal
Inhalation
Bite of infected tick
Pasteurella multocida
Soft tissue infection
-cat or dog bite
Coxiella
New bacterial species closely related to legionella
Coxiella burnetii
Gram negative
Small coccobacilli
Causes Q-fever
Low infectious dose
Soil and animal sources
Coxiella burnetii type of pathogen
Obligate intracellular pathogen
-prefers macrophages and phagocytic cells
Preferred port of entry in lung
Coxiella Virulence Factors
LPS
Type IV secretion system
Resistant to low pH and enzyme of phagolysomes
CCV-coxiella contains vacuole
Biphasic life cycle
CCV
Coxiella contains vacuole
Phagolysome like compartment where coxiella replicates
Biphasic life cycle
Small cell variants
Large cell variant
Small cell variants
Not metabolically active
Like a spore is restart to environmental
Large cell variant
Metabolically active form
After invasion of host cells coxiella swtiches from SCV to LCV
Coxiella pathogenesis
Aerosol transmission -inhaled into lungs
Binds to alveolar macrophages and is passively taken up through phagocytosis
Affinity for reticuloendothelial system
Can also invade non phagocytic cells
Intracellular trafficking of coxiella burnetii
Once in a phagosome-lysomal fusion occurs
The coxiella expands the compartment size creating a CCV
transition to the metabolically active LCV and begins to replicate-takes 6 days
Clinical features of Q fever
Symptoms begin 20 days after inhalation
Flu like symptoms
Nonproductive cough
Abnormal liver function
Q fever treatment
Most people recover without antibiotics
2 weeks with doxycycline
Sylvatic cycle
Fleas leave an infected rodent and pass the infection to other in the population. Rarely transmits disease to humans
Urban Cycle
Masses of rats in close contact with humans, infected with fleas that bite humans and transmit the infection to many
Pneumonic plaque
Results when humans infected with Y. Pestis develop bacteremia where it can infect the lungs leading to person to person spread
Yersinia pestis
Gram negative
Bacillus
Nonmotile
Virulence factors of Y. Pestis
Phospholipase D resist antibacterial factors in flea gut
Starves fleas making them constantly vomit bacteria into wound. Coagulase and polysaccharide biofilm
Yops (y pestis)
Two types of proteins
1 destroy host cells
2 disrupt host cells
Y Pestis one inside professional phagocytes effector
yops disrupt host cells
Eventually y pestis enter bloodstream
Reach regional lymph node and produce bubo
Bubo
Hemorrhagic suppurative lymphadenitis
Bacteremia—> toxic shock-LPS endotoxin, yops, protease and extracellular products
Y pestis (palgue) diagnosis
Gram stained smears of aspirates from bubo show bipolar staining gram negative bacilli
Y pestis treatment
Gentamicin or streptomycin
Brucella abortus
Gram negative rods
Non motile
Aerobes
-cannot ferment carbohydrates
Slow growing
Brucella abortus unusual envelope
Phosphatidyucholine resembles eukaryotic cells
Brucellosis
Chronic infection persist for life
Reproductive organs: infects mammary glands, uterus placenta, seminal vehicle, and epididymis
Causes abortion, sterility and decreased milk production in cattle goats and hogs
Brucellosis is spread
By direct connect with infected tissues and ingestion of contaiminated feed
Systematic control
Of brucellosis is effective at preventing infections
- vaccination of animals
- eradication of infected animals
Brucella Type of parasite
Faculatative intracelluar parasite of epithelial cells and phagocytes
Brucella once past skin or mucous membrane barrier
Able to evade innate immunity-specifically TLRs
-outer membrane lipids resemble eukaryotes
Brucella multiply in mar crop hates in
The liver sinusoids spleen bone marrow and reticuloendothelial system
-forming granulomas
Brucella intracellular survival is
Depending on inhibition of phagosome lysome fusion and apoptosis of host cell
Type IV secretion system similarly to legionella
Brucella in placenta
In cows presence of erythritol stimulate growth
Humans don’t have it. Can’t infect placenta
Brucella Immunity
Antibodies are formed but likely not protective
T cell mediated immune response is critical to control of disease
Th1 responses with cytokines associated with clearing of Brucella from macrophages
Symptoms of Brucellosis
7 to 21 days after infection
Periodic drenching night sweats (undulant fever)
Enlarged lymph noddes
Splenomegaly is most common
Brucella diagnosis
Doxyclcine in com one with rifampin
No vaccine for humans
Slow growth requires long incubation periods
Francisella tularnesis
Gram negative
Non motile
Aerobic
Causes rabbit fever tularemia
Francisella tularensis type of parasite
Faculatative intracellular parasite
Aerobic and requires cysteine for growth
Francisella tularensis Tier
Tier 1
Low infectious dose
Ease of spread
High virulence
Francisella tularensis Virulence factors
Lipid rich capsule
Unusual LPS
Natural infection confer long lasting immunity
-antibody tigers remain high for many years
Francisella tularensis LPS
Doesn’t stimulate innate immunity (unusual) BUT LPS does induce protective antibodies
Tularemia spread by
Contact with an infected mammal or blood feeding arthropod
Rabbits squirrels can be infected without any symptoms
Low infectious dose
Not found in British isles Africa South America or Australia 100-200 cases per year
Francisella tularensis minor routes of infection
Minor skin abrasion
Inhalation
Francisella tularensis LPS is
Not recognized by innate immune system (TLR)
Tularemia lesion
Often develops at site of infection and becomes ulcerated
Tularemia after macrophage ingestion
Resides in opahgosome
Resist lysome fusion and escapes to host cytoplasm
Francisella tularensis can multiple in many cell types
Hepactocytes kinda alveolar epithelial cells
Infects reticuloendothelial organs often forming granulomas
Granulomas
Type of inflammation
Collection of immune cells -macrophages
Occurs when the body attempts to wall off a foreign substance that it cant eliminate
Tularemia-clinical aspects
Incubation period 2 to 5 days
Disease progression depends on site of inoculation and extent of spread
All cases begin with acute onset of high fever
Tularemia disease depends on site of inoculations
Ulceroglandular form Oculoglandular form Oropharyngeal form Pneumonic form Typhoid also form
Ulceroglandular form of tularemia
Most common
Tick bite or handling infected animal
Ulcer forms and swollen lymph nodes
Pneumonic form tularemia
Most serious form
Inhalation of contaiminated dust or aerosols restyle in pneumonic tularemia or infection similarly to typhoidal form
tularemic pneymonica can also develop through bacteremia
Typhoidal form of tularemia
Combination of the general symptoms without locating symptoms of other syndromes
tularemia treatment
Treatable with antibiotics
Live attenuated vaccine is available for high risk populations
Pasteurella multocida
Gram negative
Susceptible to penicillin unlike most gram negative rods
Normal respiratory flora of many dogs and cats
Pasteurella multocida Type of parasite
Facultative anaerobes
Oxidase positive ferements a variety of carbohydrates
Pasteurella multocida common causes
Most common is dog/cat bite or scratch
Soft tissue infection usually develops within 24 hours of animal bite or scratch
Diffuse cellulitis with a well defined erythematous border
Vibrio Cholerae pH and why
Preferred pH 8-9.5 produces cholera toxins
2 main biotypes can cause cholera
Classical
El Tor
Vibrio cholerae can produce what in the environment
Biofilm
V. Cholerae virulence factors
Flagella
Pili to adhere to mucosal tissue
V cholerae pili
Allow to adhere to mucosal tissue
Shift from saltwater to reduced ion levels found in body leads to expression of pili and to the toxin
Main regulator of pathogenicity island and ToxR
Cholera toxin
Phage encoded
Cholera toxin leads to
Excessive accumulation of cAMP
This causes hypersecretion of
Cl
K
Bicarbonate
Cholera is spread
By contaminated water
Humans can spread the disease
Cholerae incubation period
2 days
______inoculum is needed to cause disease
High
Only 01 and 0139 can cause disease
Effect of cholera toxin
Can lose many liters a day
-no WBC/RBC
Fluid contains a significant amount of K and Bicarbone which can lead to hypokemia and metabolic acidosis
Enterotoxigneic Coli is the leading
Cause of morbidity and mortality in children under 2
Also travelers diarrhea
E. Coli transmitted by
Contaminated food and water
E. Coli colozines what
Proximal small intestine
Must adhere to cause disease
Enterotoxigenic Coli adherence factors
Colonizing factor CF pili
E. Coli 2 toxins
Heat label toxin
Heat stable toxin
Heat labile toxin (E. Coli)
A-B toxin in an enterocyte it leads to secretion of chloride ions, blockade of NaCl reabsorption
Heat stable toxin (ST) (E. Coli)
Binds to cell leading to signaling cascade that ends with fluid and electrolyte secretion
E. Coli Immunity
Let and CF specific SLgA
No inflammation
How to rule of vibrio cholerae for diarrhea
Have eaten shellfish or been to an endemic area
Thiosulfat citrate bile sucrose agar
Agglutination test (el tor strain)
Serological testing
Inoculate plates with diluted stool samples
Not very Reich medium so fastidious G wont grow
Aerobic incubation kills the anaerobes
Treatment for secondary diarrhea agents
Oral rehydration
-mix of sugar and salt
Antibiotics can help shorten duration or reduce severity
Secretory diarrhea antibiotics
Tetracyclines for vibrio infections-doxycycline
2nd generations fluorquionolones for ETEC- ciprofloxacin
E. Coli and V. Cholerae
Small intestine Copious amounts of watery stool No blood in stool No leukocytes in stool No tissue damage
Invasive Bacterial Pathogens (salmonella, shigella)
Large intestine Small volume of stool Bloody stool Leukocytes in stool Tissue ulcerations
Enterohemorrhagic e. Coli and Enteropathogenic E. coli
Lower small intestine/Upper large intestine
Colonization causes attaching and effecting lesion
Blood in stool and possibly urine
Urinary Tract Infections
UTIs are the most common form of bacterial infection of an organ system (not including the mouth) and the most frequent cause of doctors vistas by adaults
Cystitis
Inflammation in the bladder
Uncomplicated UTI
All normal defense mechanisms are intact
No recent hospital admissions
Disease limited to lower urinary tract
Usually UPEC or other commensalism E. Coli
Complicated UTI
Some structural abnormality in urinary tract
Recently admitted to hospital
Disease mot likely will spread to kidneys
Usually other Enterobacteriacea
Natural defenses found in urinary tract
Complete voidance of bladder peristalsis Ureterovescile valves Mucous layer PH
Pyelonephritis (kidney infection)
Cystitis can spread to the kidney via retrograde flow from the bladder to the kidneys
- neurologic disorders
- uterovescile valves not fully formed in kids
- Pregnancy hormones
Urethral catheters
Urinary tract stones
UPEC - Uropathogenic E. Coli
Type 1 Pili
P Pili are needed for ascending infections
Can invade superficial epithelial cells
Alpha hemolysin and cytotoxic necrotizing factor cause injury
Additional cause of uncomplicated UTI
Proteus mirabilis
Proteus mirabilis
Occurs in uncomplicated and nosocomial infection, abnormal urinary tract structure more likely to have UTI caused by P. Mirabilis
Which UTI is more severe P mirabilis or E. Coli induced
P mirabilis
P. Mirabilis virulence factors
Flagella
An adhesion on the fimbriae is specific for urinary epithelium
Hemolysins
IgA protease
Urease an enzyme that readies the pH of urine
Proteus mirabilis urease
An enzyme that raises the pH of urine
Urea—> 2 NH3 + CO2
Bacteria will grow better in the less acidic environment
Toxic to renal cells
Enhances formation of struvite urianry stones which can lead to a chronic infection
UTI Diagnosis
Surprisingly difficult to positively ID the causative agent of a UTI
Count bacteria in the urine
Proteus can be diagnosed by alkaline urine and urease
Dysuria
Painful urination
Pyuria
WBC/pus in urine
UTI treatment
Variety of antimicrobials
TMP/SMX first choice
Klebsiella
Nonmotile, pili aid in adherence
Capsule contributes to growth phenotype of large mucous colonies
Usually infect the respiratory and urinary epithelium
Type 1 Pili (klebsiella)
Important for adherence to urinary tract epithelial cells
Type 3 pili (klebsiella)
Important for adherence to respiratory tract epithelial cells
Klebsiella enterotoxin is similar to ___ and ___
ST
LT
So they can induce secretory diarrhea
Aerobactin
An iron sequestering protein
Primary klebsiella virulence factor
Antiphagocytic capsule
K. Pneumonia type 258
Infamous for being multi drug resistant
Implicated in hospital acquired respiratory urinary tract and blood stream infection
helicobacter pylori Type of pathogen
Microaerophilic slow growth
helicobacter pylori can colonize what
The stomach
helicobacter pylori secretes
Urease
-raises the pH
Vacuolating cytotoxin (helicobacter pylori)
Can cause apoptosis of host cells
helicobacter pylori mode of transmission
Unknown but likely fecal-oral or even oral-oral route
helicobacter pylori identified as a __
Class I Carcinogen
helicobacter pylori Cag+ can lead to
The development of gastric adenocarcinoma or gastric mucosa associated lymphoid tissue lymphoma
Type IV secretion system (helicobacter pylori)
Injects VacA and Cag into gastric epithelial cells
H. Pylori uses flagella to
Propel itself into the mucus layer where it secretes even more urease.
Outer membrane proteins of H. Pylori are used to
Adhere to gastric epithelial cells
helicobacter pylori causes inflammation which results in
Epithelial cell death and ulcer formation
helicobacter pylori inflammatory effector molecules cause epithelial to produce _______
IL-8
helicobacter pylori downregulation of somatostatin producing
D-cells
H pylori infection can lead to many different diseases
Peptic ulcer disease
Chronic superficial gastritis
Lymphoproliferative disease
Chronic strophic gastritis —>adenocarcinoma
helicobacter pylori primary infection can be
Silent or can lead to nausea/upper abdominal pain
Can also cause non-specific symptoms such as belching , heartburn, dysphasia, globes sensation
Diagnosis of H. Pylori
Urea breath test
Urea Breath Test
Patient ingests a labeled urea.
Urease in stomach can break it down into a labeled CO2 that can be exhaled and quantified
H. pylori treatment
2 lines of treatment with many side effects
H. Pylori First line of treatment
Proton pump inhibitor
Antibiotic cocktail
-usually clarithromycin and metronidazole or amoxicillin
H. Pylori second line of treatment
Proton pump inhibitor
Bismuth subsalicylate
Tetracycline 500 mg
Metronidazole 500 mg
What is a mucosal surface
Surface that interacts with air that has associated glands for secreting mucus
Defense of mucosal surfaces
Innate immunity
Adaptive immunity
No specific barrier defenses
Transmission of gram-Negative mucosal pathogens
Feces to mouth via any of the seven Fs
Feces Food Fluids Fingers Flies Fomites Fortification
Natural barrier Defenses of GI tract
Acidity
Motility
Mucous layer and underlying glycocalyx
Tight junctions
Lysozyme (muramidase)
Cleaves B 1,4-glycosidic linkages between N-acetylnuramic acid and N-acetylyglucosamine
Murein can be
Exposed or hidden
Secretory antimicrobial compounds
Lysozyme Lactoferrin Cathelicidin Defensins Secretory immunoglobulins
Lysozyme
Cleaves linkage between N-acetylnuramic acid and N-acetylglucosamine
Lactoferrin
Bacteriostataic effects via sequestering iron
Cathelicidin
Disrupts bacterial membranes of Gm- and Gm+ as well as fungi
Defensins
Creates pores in microbes
Alpha defensins produced by neutrophils and paneth cells (in intestines)
B defensins produced by epithelial cells
How do pathogenic bacteria overcome these innate barrier defenses
Acid resistance
Fimbriae/pili
Bacterial structures
Acid resistance
Microbes with low infectious dose to tend to be acid resistant
Shigella
Enteroinvasisve E. Coli
Fimbriae/Pili (barriers of defense)
Adhere to tissue to resist being shed
Bacterial structures (barrier defense)
Gram-/Gram+ cell membrane sensitivities to bactericides compounds
Cationic amino acids into cell membrane sensitivities to bactericidal compounds
Siderophores to sequester iron in low iron environments. (E. Coli)
Macrophage as an important component of mucosal immunity
Macrophages recognize microbes via pattern recognition receptors. This leads to activation of the macrophages and the ability to kill many microbes
Activation of pattern recognition receptors also initiates
The inflammatory response
Enterobacteriaceae family
Gram -
Nonspore forming
Non acid fast rod
Facultative growth
ALL have endotoxin some secrete exotoxins
Enterobacteriaceae family Cell wall components
O antigen
K antigen
H antigen
O antigen
Outer antigen LPS
K antigen
Polysaccharide capsule
H antigen
Flagella
2 most common infections of enterobacteriaceae
UTIs
Acute Diarrhea
Escherichia coli
Most E. Coli ferment lactose and produce indole
Use O, K, and H antigens to determine serotype
E. Coli Pili: Type 1
Most common bind D-mannose residues on epithelial cells has on/off switch
E. Coli Pili: P pili
Bind diglactoside found within urinary tract and some erythrocytes
E. Coli Pili: other
Common to diarrheal strains bind to enterocytes
E. Coli toxins: alpha hemolysin
Pore forming cytoxin
E. Coli toxins: Cytotoxic necrotizing factor
CNF
A-B toxin that produces G proteins (disrupts intracellular signaling). Often made with alpha hemolysin
E. Coli toxins: Shiga toxin
(Stx)
A-B toxin that blocks protein synthesis by ribosomal modification
UPEC
Uropathogenic E. Coli
ETEC
Enterotoxigenic E. Coli
EPEC
Enteropathogenic E. Coli
EIEC
Enteroinvasive E. Coli
EHEC
Enterohemorrhagic E. coli
EAEC
Enteroaggregative E. Coli
Bundle forming pili
EPEC uses to adhere to distal small intestinal enterocytes
Type III secretion system: EPEC
Inject over 30 E. Coli secretion proteins into host cell
EPEC: Intimin-Tir
Interaction leads to formation of attaching and effacing lesion
EHEC produces toxins that leads to
Hemolytic uremic syndrome
Associated with bloody diarrhea
EHEC source
Animal products, unpasteurized juices, fresh vegetables
Most common EHEC
E. coli 0157:H7
EHEC primary reservoir
Cattle
EHEC produces
A shiga toxin
- hemorrhagic colitis
- hemolytic uremic syndrome
EHEC causes an attaching
Effacing lesion in colon via long polar fimbriae lead to A/E lesions similar to EPEC
Shiga toxins attack what
Mucosal surfaces are heavily vascularized, shiga toxins attack small blood vessels of the large intestines
-This can be intensified when inflammatory cytokines are present
EIEC is similar to
Shigella and causes a disease that is milder versions of shigellosis
- children under 5
- usually contaminated food/water
- humans only reservoir
EAEC can lead to
Watery diarrhea that can last longer than 14 days
Involves tight adherence to epithelial cells in a stacked brick pattern
Hallmarks of intestinal E. Coli infection
Symptoms usually begin a couple of days after inoculation and is self limiting
Exceptions: EAEC diarrhea can last for weeks
EPEC can become chronic
EHEC and EIEC can have bloody diarrhea
E. Coli treatment
Diarrheal disease-supportive therapy, keep hydrated if needed
-Hemorrhagic colitis/HUS may require hemodialysis/hemispheres is
ABX can be reduced duration of diarrhea but usually not needed
Antimotility agents are contraindicated, especially for EIEC and EHEC
Shigella is specialzied
E. Coli
All species are invasive and multiple within epithelial cells
Shigella antigens
O and K
-O antigens are main
NO H antigens
Shigella produce
Shiga toxin
Shigella Species
Shigella dysenteria
Shigella Flexneri
Shigella Boydii
Shigella Sonnei
Subgroups found within each of these
Which shigella spp. Cause most severe disease
Shigella dysenteriae (serogroup A) Type 1
Shigellosis
Strictly human disease
Can be spread by food/water contaminated by humans (oral/fecal)
Incidence and prevalence is directly related to personal and community sanitation
Wars and disasters enable outbreaks
Shigellosis inoculum
Very low little as little as 10 organisms
-acid resistant
Shigella pathogenesis
Mucosal surface is resistant to infection but basal surface is not
1) enter M cells, via outer membrane proteins called invasion plasmid antigens. Transcytose through M cell to a macrophage
2 escapes phagosome, causes apoptosis of macrophage, bacteria can now escape dead macrophage in the lamina propria
3 Type III secretion system is used to inject invasion plasmid antigens via the absolute real surface of an enterocyte (NOT an M cell)
4 Host cell cytoskeleton rearrangements occur to help internalize shigella via endocytosis
5 Shigella use host actin to move inside the host cell
When does an ulcer form during shigella
An ulcer develops when invaded cells die and slough off
-ulcers also allow shigella to reach the lamina propria
All species of shigella induce what
An inflammatory diarrhea with leukocytes in the stool
S. Sonnei induces a watery stool still with leukocytes
Shigella dysenteriae type 1 is different
Significant mortality even in healthy individuals
Produces Shiga toxin
- kills intestinal epitheal and endothelial cells
- Disrupts Na absorption
- Toxin can be systemic
Shigella immunity
Infection does produce immunologic protection however there is NO CROSS PROTECTION against other serotypes
Shigella diagnosis
Stool culture
O antigen agglutination tests to determine serotype
Shigella treatment
Usually self limiting
Antibiotics such as ciprofloxacin and azithromycin can help shorten the illness period
Salmonella infection
Fecal (human or animal)—oral transmission
More acid sensitive than shigellae
Low pH induces the expression of what in salmonella
Expression of at least 40 proteins found on pathogenicity islands on large virulence plasmids
Salmonella pathogenesis (5 steps)
1 Orgnaims make contact with M cell and injects effector molecules into cell with Type III secretion system
2 These events induce surface ruffles and uptake of the organisms
3 Multiples and remains within cell vesicles for many hours
4 Organims related to lamina propria inflammatory response is activated ingested by phagocytes then kills phagocyte
5 Macs engulf most but some escape to cause a transient bacteremia
—typhoid serovars will survive and grow within the macrophages
Salmonella Typhi
No animal reservoir
Strictly human pathogen
Asymptoamtic carriers
Carries have colonized gall bladders and the organims can be cultured from their feces
Salmonella typhi survival in macrophages
Within macrophages they can live longer than other serovars due to its ability to inhibit the oxidative burst
-Enters lymphatic system via macrophage
Endotoxin causes fever
