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Microbiology II


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MS and bug cause possibility
1) MS is an inflammatory demyelinating autoimmune disease of the CNS
2) more prevalent than evolution woudl suggest if genetic
3) studies show that bug could cause it if it had protein resembling myelin--could cause molecular mimicry/cross reactivity
2 possible culprits of MS myelin mimicry
1) Herpesvirus 6
2) chlamydia pneumoniae
Other potetntial neuro disease-bug matches
1) PANDAS: Group A strep
2) Alzheimers: Chlamydia pneumoniae, HSV-1
3) Schizophrenia: HSV-2
Name 2 pathogens that may cause atherosclerosis
1) chamydia pneumoniae
2) cytomegalovirus

(but both are ubiquitus)
What all might chlamydia pneumoniae be involved in?
1) lung infections
2) MS
3) Alzheimers
4) atherosclerosis
5) asthma
Clinical syndromes associated with UTIs
1) cystitis (bladder, urethra). Burning, frequent urination, suprapubic pain.

2) Pyelonephritis (kidney). Fever, flank pain, nausea, vomiting, sweats. May have macteremia, renal scarring.

3) Asymptomatic bacteriuria

4) Nosocomial UTI: occurs in cataherized patients. Most common nosocomial infection.
Host factors affecting UTI susceptibility
1) mechanical defenses (flushing action of urine)
2) anatomical factors (shorter urethra in women; anticrobials in male urethra)
3) predisposing factors: stones, strictures, catheters in urethra
4) normal flora provides protection
5) density of receptors for pathogen adherence affects susceptibility
Common features of UTI pathogenesis
1) pathoens originate from intestinal tract
2) bug adheres to uroepithelium; invades epithelial cells; causes inflammatory response and exfoliation
3) Recurrent infection may be due to reinnoculation or from reservoir of survivors in bladder biofilm
What is the most important virulence factor for UPEC?
Ability to adhere specifically to uroepithelial cells, which is determined by the expression of fibrial adhesins by the bacteria.
More on UPEC and adhesins
1) most strains can express multiple adhesins
2) each adhesin binds to a distinct cellular receptor
Important point on UPEC adhesins and type of infection
The adhesins expressed by the bacteria and the distribution of the receptors for those adhesins on different cell and tissue types will greatly influence the type of infection that occurs.

The density of the receptors expressed on epithelial cells can make individual more or less susceptible to UTI
What happens to UPEC after attachment?
1) bug replicates and grows a biofilm on the inner surface of the bladder.
2) some bugs invade bladder epithelial cells and replicate to high levels within the cells
3) intracellular bugs are protected from host defenses and maybe from Ab treatment--these may be source of relapse
4) host then may try to exfoliate the infected cells
What largely causes UTI symptoms?
Inflammatory response to the infection, which is elicited primarily by LPS. More attachment-->more LPS-induced inflammation
Facts on nosocomial UTI
1) 50% of short term catheterized get one; 100% of >28 day get them
2) many bugs can cause it
3) may be from hands of health care personell during insertion or adjustment
4) Infecting strains often don't stick well to epithelium and don't express adhesins
5) but they do stick well to plastic
6) form biofilm on catheter; eventually occlude lumen
Why do catheters get infected so often?
1) the foreign body provides an attachment site
2) bugs growing on body form a biofilm, making it hard for immune cells or Ab to get inside
3) localized immunosuppression occurs in the vicinity of the foreign body
Staph saprophyticus and UTIs
1) second most common UTI causer in young sexually active women
2) can cause cystitis
3) maybe causes pyelonephritis
4) NO FIMBRIAE, though it does selectively adhere to uroepithelium
Diagnosis of UTI
1) by culture: tho urine often contaminated
2) Quantitative: measure cfu/mL in the urine
3) Practically: if they have typical symptuoms and pyuria (WBC in urine)
Treatment of UTI
1) cystitis: single dose/short course Ab
2) pyelonephritis; >2 wk oral or IV ab
3) nosocomial UTI: AB and removal of body
What causes bacterial vaginosis
1) consequence of complex change in vaginal flora
2) Lactobacillus suppressed...
3)...overgrowth of Gardnerella vaginalis, Mycoplasma hominiss, other aerobes
symptoms of BV
1) fishy smelling discharge
2) little inflammation
3) many may be asymptomatic
Pathophysiology of BV
1) newly dominant anaerobes make proteolytic enzymes that chew up vaginal polyamines
2) vaginal pH rises, polyamines volatalize and smell
3) these changes cause transudation of vaginal fluid and exfoliation of epithelial cells --> discharge
Diagnosis of BV
Need 3 of these 4:

1) presence of "clue cells" (exfoliated epithelial cells + Gardnerella)
2) vaginal pH > 4.5
3) homogeneous adherent discharge
4) "amine whiff test": fishy odor after adding KOH to discharge
Complications associated with BV
associated with increased risk of :

1) PID
2) pre term labor
3) low birthweight infants
4) postpartum infection
5) miscarriage
What does the rate of movement of an STD thru a population depend on?
1) transmissibility of the infectious agent
2) rate of new partner acquisition
3) partner's sexual history
4) duration of infectiousness
Who sustains STDs in the population?
A small number of people who have a large number of sex partners
Name the major bacterial agents of STDs:
Chlamydia trachomatis
Neisseria gonorrhea
Treponema pallidum (syphilis)
Haemophilus ducreyi (chancroid)
Common features of STD agents and infections
1) Nearly all STD agents are sensitive to physical & chemical factors (almost never found free in environment)

2) all are obligate human pathogens with no animal reservoir (reservoir is asymptomatic but infectious human carrier)

3) Asymptomatic disease is common

4) agenst not effectively eliminated by specific immune responses

5) no effective vaccines exist, EXCEPT for hepatitis B
Three Chlamydia species that cause human infection:
1) C. trachomatis
2) C. psittaci
3) C. pneumoniae
different strains (serovars) of C. trachomatis
1) Ocular strains
2) genital strains
3) Lymphogranuloma venereum strains (LGV)
Ocular C. trachomatis details
1) cause TRACHOMA: the most common cause of preventable blindness

2) infect the eye epithelium, cause conjunctival inflammation and vascularization/scarring of cornea

3) eyelid turns inward due to scarring; makes eyelashes continually abrade cornea

4) secondary corneal infection after corneal ulceration is what causes blindness
Overview details of genital strains of C. trachomatis
1) most common STD pathogen in the world
2) by age 30, 50% of sex active women show evidence of past infection
3) infection often asymptomatic but can cause extensive genital tract damage
PRoblems caused by genital strain of C. trachomatis
1) urethritis: 1/2 men asymptomatic. Symptoms include dysuria and urethral discharge. Sequelae: epididymitis, prostatitis, procitis

2) Cervicitis: 70% of women are asymptomatic. Sequlae: endometritis, salpingitis, and perihepatitis
65% of women with gonorrhea also have...
C. trachomatis--so choose AB appropriate to both
Chlamydial infeection in pregnancy
Can lead to:

1) miscarriage
2) premature birth
3) low birth weight

Can cause conjunctivitis and/or pneumonia in infant. If untreated, baby can get a chronic respiratory disease syndrome.
LGV strain of c. trachomatis details
1) most invasive of the 3 strains (ocular and genital)
2) endemic in africa, asia, SA, carribean
Presentation, symptoms, and progression of LGV (lymphogranuloma venereum) strains
1) cause initial urethritis or cervicitis
2) rapidly penetrate thru genital mucosa, infecting monocytes & macrophages and causing systemic infection
3) usual presentation is a characteristic INGUINAL LYMPHADENOPATHY or sometimes a genital ulcer. May be anorectal involvment
4) chronic lesions can lead to lymphatic obstruction, rectal stricutres, fistulae, and EXTENSIVE DESTRUCTION OF EXTERNAL FEMALE GENITALIA
Basic facts of Chlamydia psittaci
1) primarily animal pathogen; comomon in birds or mammals
2) when infected birds are stressed or overcrowded (chicken coop), they shed C. psittaci in feces
3) bug can then infect humans that inhale aerosolized feces dust of the birds
Chlamydia psittaci symptoms
Causes flu-like respiratory infection.

Can become systemic and cause damage to heart valves
What is the most prevalent chlamydial pathogen in human populations?
Chlamydia pneumoniae
What does c. pneumoniae cause?
Acute respiratory illlness, maybe chronic respiratory infection

Also MAYBE: cardiovascular disease, and a bunch of other chronic diseases
General characteristics of Chlamydia
1) obligate intracellular parasite
2) Gell envelope gram negative-like; has LPS but NO PEPTIDOGLYCAN
Developmental cycle of chlamydia
(takes 2-4 days)

1) Elementary body (EB) attaches to columnar epithelial cells of mucosa
2) internalized via RME
3) inside endocytic vescicles, EBs prevent acidification
4) EBs convert to LARGER, METABOLICALLY ACTIVE RBs (Reticulate bodies)
5) RBs use host mito and ATP to grow and divide
6) vesicle expands and fills with RBs (called an INCLUSION)
7) RBs transform to the metab-inactive but infectious EBs
8) EB's released from cell, infect new cells
What causes scarring and damage to fallopian tubes in C. trachomatis infection?
Cellular immune response--activation of NK cells, cytotoxic T cells, macrophages, etc
1) doxycycline and azithromycin
2) Why? Because you MUST have a AB that can penetrate host cells and reach sufficient INTRACELLULAR concentrations to kill the bug
Diagnosis of Chlamydia
1) used to be hard--relied on slow culture and microscopy

2) now can use PCR or LCR-based analysis of urine. But may be oversensitive--may detect presence of inviable organism
Chlamydia: gram neg or pos?
What causes syphillis
Treponema pallidum
T. Pallidum reservoirs?
Only humans
T. pallidum staining
visualized by dark field microscopy; stains poorly with other dyes
What shape is Syphillis bug?
(Treponema pallidum)

Spirochete with tapered ends
Other structural characteristics of Treponema pallidum
1) stains with dark field miccro
2) spirochete
3) motile with periplasmic flagella at each end (if pathogenic)
4) Gram neg-like double membrane, but no LPS in outer membrane
5) instead, has TROMPS: Trepmonemal rare outer membrane proteins
6) never has been continueously cultivated in vitro
7) can be cultivated from rabit nads
What T does T. pallidum survive best at?
34 C: so the skin is principal site of multiplication
Syphillis clinical disease presentation
(treponema pallidum)

1) 3 week incubation period

2) primary stage: dermal Chancre develops at site of innoculation. Lasts 2-6 weeks

3) Secondary stage: generalized cutaneous rash, especially on palms and soles. Usually appears 2-8 weeks after appearance of chancre. Also: low grade fever, lymphadenopatthy, mucous patches in mouth or GU tract, anal wart thingees.

4) Latent stage: subclinical infection. Months to years.

5) [30%]: Tertiary stage. Years or decades later. Any organ can be involved. Destruction of tissue results from host response to trepoonemal antigens. But few treponemes are present in this stage
Can symphillis be passed to baby?
yes--congenital syphillis exists
when do syphillis patients begin to develop immunity?
They begin to develop immunity sometime after appearance of chanre. But if they are treated at this pt, they show little immunity. People treated later show varying degrees of immunity.
Diagnosis of T. pallidum
1) Examine exudate frmo chancre, rash (as long as it is not oral or anel) for presence of treponemes in dark field scope

2)Serologic tests
a) NON TREPONEMAL TESTS: detect ABS against cariolipin. Ex: VDRL, RPR. Rapid, cheap syphillis screening tests. Poor sensitivity and specificity
b) TREPONEMAL TESTS: screen for ABs against cultivated T. pallidum. Lower rate of falso positives (better specificity). Expensive
What is the treatment of choice for Syphillis?

No known resistance
Where is syphillis geographically focuses?

Urban areas with large MSM populations
Describe the "two tiered" screening process for diagnosis of syphillis?
1) cheap screen with non-treponemal test for ABs against cardiolipin

2) expensive, more sensitive test for ABs agains treponeme
Basic facts on all neisseria species
All are gram neg diplococci

All are ox-pos

(differ in sugar utilization)
Do gonococcal infected people develop immunity to reinfection?
Description of gonococcal infections
1) Simple: urethritis in men, cervicitis in women
2) If symptomatic: purulent discharge
3) up to 50% asymptomatic
4) in 15% of wone, GC may infect fallopian tubes and cause PID
5) In a small percentage, you get DGI
6) GC infection increases reisk of HIV infection/transmission
What is DGI?
Disseminated gonococcal infection

Bacteremia-arthritis syndrome where GC gets in blood and localizes to skin and joints.

Only 1-2% of cases
Do Neisseria species make exotoxin?
Neisseria gonorrhea virulence factors
2) Pili (fimbriae): both species. Attachment to host tissues
3) LPS: functions as adhesin; also causes tissue damage
4) other outer membrane proteins that function as adhesins
Neisseria gonorrhea AB resistance
18% have some resistance.

1) low level penn resistance: due to chromosomal mutations

2) high level penn resistance: dus to b-lactamase production (plasmid)

3) tet resistance: plasmid

4) growing ciprofloxacin resistance
Diagnosis of n. gonorrhea
1) men: gram stain urethral exudate for g-neg diplococci

2) women: had to culture vaginal flora until recently

3) new, amplification based rapid tests taht can be performed on urine as well as cervical/urethral specimens
Treatment of gonorrhea
1) ceftriaxone (cephalosporin not cleaved by B-lactamase)


2) tetracillcine or a macrolide to treat fro likely coexistent chlamydia (40% of gono cases)
Vaccine for the rrhea?

1) antigenic variability
2) poor immune responses at genital mucosa
Clinical featuures of meningococcus infection?
1) nasopharyngeal colonization (usually asymptomatic)
2) meningococcemia: gets into blood. Death may come in as little as 6 hours, because LPS endotoxin causes DIC (disseminated intravascular coagulation)
3) 10% die even with treatment
4) 10% of survavors have severe aftereffects
Key signs of meningococcemia
1) petechial rash: pinpoint purplish red lesions caused by hemorrhage in intradermal vascular bed

2) purpura fulminans: large areas of confluent necrosis of the skina s a result of DIC (disseminated intravascular coagulation)
What can cause susceptibility to repeated disseminated neisseria infections?
Late comlement cascade deficiencies
What else contributes to susceptipility to disease with neisseria, when a lot of people have it in their nose?
Amoount of anti-capsule antiibody correlates with susceptibilty to infection
Meningococcus virulence factors
1) high antigenic variation (like GC)
2) polysaccharide capsule (UNLIKE GC)--Note: ALL BACS that cause meningitis have a CAPSULE!!!
3) pili and proten adhesins
4) LPS: responsitble for tissue damage, petichial rash, etc. Invariant lipid A (exotoxin)
Common thread among all bugs that cause meningitis
All have a polysaccharide capsule
Therapy for n. meningitidis
Must have an AB that penetrates CSF
N. meningitdis vaccine
1) mutivalent vaccine composed of mixture of strains fo capsular polysaccharides
2) works in adults, but not in very young kids
3) Group B polysaccharide perfectly mimics a brain antigen, so it is not immunogenic and there is NO VACCINE FOR GROUP B INFECTIONS
new n. menengitidis vaccine
Group C capsular polysaccharide CONJUGATE vaccine
What is the causative agent of texas cattle fever?
Something transmitted by TICKS
What populations do vector borne infectious diseases disproportionally hit?
Poor tropical countries. See malaria.
Describe the cycle of vector-borne transmission
1) arthropod gets infected when feeding on infected host AFTER its INTRINSIC INCUBATION PERIOD (period after host infection after which it becomes infectious to subsequent feeders)

2) Infected arthropod then may transmit the disease to other naiive hosts, after its EXTRINSIC INCUBATION PERIOD. Also, there is no transmission to the new naive host unless the feeding is LONG enough--the "grace period).
Path of pathogen in the arthropod
In thru the gut. Out through the spit.
Pathogen-vector specificity
Pathogens are HIGHLY ADAPTED to the vectors that transmit them.

Why are most vector borne diseases highly seasonal?
Vector population densities change with the seasons
Is vertical transmission of pathogen between vectors common?
No. But many rickettsia species in ticks are transmitted vertically.
What agent causes Lyme diseasae
Borrelia burdorferi

Similarities and differences: borellia burgdorferi and treponema pallidum
Simiarities: spirochetes

Differences: borellia can be grown in culture, unlike treponema which can only sort of be cultivated in rabbit nads
What species of tick carries borellia burgdorferi
(a spirochete)

Vector: Ixodes scapularis, Ixodes pacificus, Ixodes rcinus
Where is most lime disease found
NE, and wisconsin area?
Clinical progression of Lyme disease
1) "eryhema migrans" rash soon after bite at bite site. Sometimes with central clearing. May have fever, chills, ache. Treatable by AB here.

2) 7-30 days later. Patients develop arthritis; some cases have neuro and cardio involvement

3) chronic arthritis and CNS disease
Diagnosis of Lyme disease
1) hard to detect the spirochetes in humans: smal numbers
2) ELISA/Western blot to detect anti-Borrelia IgM and IgG

(current diagnosis have specifisity and sensitivity problems)
Treatment of Lyme disease
1) early stage: AB treatment effective
2) later stagge: controversy over use of AB
Vaccine for Lyme
1) 1999: vaccine based on outer surface protein approved. 80% efficiency. But controversy about possibiltiy of vaccine causing arthritis.

2) 2002: vaccine removed from market

3) mechanism: ABs from the vaccinated person actually enter the tick gut and kill the borellia before it even gets in!!
Other pathogens transmitted by Ixodes scapularis in US
agent of Human granulocytic erlichiosis
Babesia microtti
Tick borne encephalitis virus
Vector borne bacteria in NC
1) rickettsia reckettsi (RMSF): dog tick

2) Erlichia chaffeensis (Human Monocytic Erlichiosis): dog tick, lone star tick
Southern tick associatd rash illness

Lyme like illneess (erythema migrans rash, flulike illness, but not b. burgdorferi caused).
General characteristics of Rickettsia
1) small coccobacilli
2) gram neg-LIKE envelope
3) obligate intracellular parasites
4) Tet susceptible
Thre genera in the rickettsae family that are a health threat
What kind of ticks carry R. rickettsii
dog dick
RM wood tick
Diagnosis of RMSF
1) prodromal symptoms within 1-2 wks: Chills, fever, HA, rash (erythematous, -->maculopapular-->petichial, extremeties-->trunk)

2) fulminant vaculitis of a lot of tissues
Infectious process of rickettsiae
1) r.r. attaches to receptors on vascular endothelial cells
2) Induced endocytosis via r.r. energy
3) internalization in endosome
4) r.r. escapes from the endosome
5) replication via parasitism of host ATP
6) ricketsia released at end of host filapodia
Effects of Rickettsia rickettsiae infection in cells
Infects vascular edothelial cells and causes:

1) increase in intracellular peroxides and ROS that damage host
2) decrease in key antioxidants that defend against ROS damage
3) oxidative damage and increased damage of endothelial and othe rtarget cells
4) Modification of vascular endothelium leads to increase of platelet adherence, pulling platelets out of circulation. This reduces platelet count, increases coag time, and sets up DIC (disseminated intravascular coagulation)
5) damaged endothelial cells are shed and block vasculature
6) occlusion leads to microthrombi and microhemorrhage (petechiae).
7) lack of perfusion can cause anoxic brain injury
8) can get edema due to leakage from BV
Diagnosis of. R. rickettsiae
1) Isolation of bug is hard. Have to innoculate viable susceptible cells since they are obligate intracellular bacs.
2) immunofluorescent demo of organisms in skni biopsies
3) MOST RAPID & SESNSITIVE & PRATICAL: seological. Latex agglutination test for detection of anti-ricketsial IgM. (but only works once you have mounted a sufficient immune response.)
Erlichia and Anaplasma basic facts
1) small, gram negative like obligate intracellulars.
2) but they replicate in VACUOLE--don't escape into cytoplasm like R. Rickettsiae
3) cause disease charachetized by fever, malais, myalgia, ha, sweat
Erclichia causing organism:
Erlichia chaffeensis agent found in Foort Chaffee, AK)
What does Erlichia chaffeensis mainly infect?
What does Anaplasma phagoctophilia mainly infect?
Morpological types of fungi
1) yeast: unicellular, reproduces by budding, can produce pseudohyphae

2) mold: multicellular, filamentous pstructures known as hyphae. Reproduces by SPORULATION (not buddint)

3) dimorphic fungus: grows like a mold at RT, but grows like yeast at body Temp
Structure of spores
(how mold phhase reproduces)

1) may be sexual or asexual (conidia)
2) spore organization used to ID fungi
Hyphae structure
septate, aseptate, color--hyaline (colorless), dematiaceous (brown/black)
Fungus cell wall v. bacteria cell wall
Only fungus has chitin and glucans
Comparing cytoplasmic membranes of bac and fung
1) fungus has no sterol, bac has sterol
Antifungals list
1) polyenes (amphotericin B, nystatin)
2) azoles (moconazole, etc)
3) anti metabolites (5-flurocysteine)
4) echinocandins (caspofungin)
5) topicals
1) amphotericin B, nystatin
2) bind to eROSTEROL in fungal membrane (no sterols in bacterial membrane) causeing loss of membrane integrity.
1) miconazole, fluconazole, et
2) inhibit SYNTHESIS of ergosterol
Anti metabolites
1) 5-fluorocystosine inhibits protein synthesis. Significantly toxic.
1) caspofungin. New. Inhibits GLUCAN synthesis--and glucan is an important component of fungal cell walls.
Dermatomycoses description
1) filamentous fungi (molds)
2) posess keratinolytic enzymes letting them parasitize all fully keratinized tissues of the body (hair, nails, skin)
3) generall ydo not penetrate deeper.
4) different ones are host and tissue specific
5) classified by colony morphology and production of conidia (spores)
Important dermatophyte infections
1) tinea cpitis (scalp): can form within hair shaft (endothrix0 and around shaft (ectothrix).

2) tinea barbae (beard)
3) tinea corporis (smooth skin0
4) tinea cruris (groin)
5) tinea pedis and tinea unguim (feet and nails)
Lab diagnosis of dermatophye fungus
1) direct microscopic examination and culture
2) ID based on colony and micro morphology
Three major kinds of subcutaneous mycoses
1) sporotrichosis
2) chromomcosis
3) mycetomas

All are soil fungi that infect subcu tissue following trauma
Sprortrichosis disease
1) usually disease of subcu tissue
2) enteres thru traumatized tissue like THORNS, sPLINTERS, and MOSS>
3) cuases painless papule after innoculation
4) ascends along lymphatic channels
5) pulmonary or disseminated sporotrichosis is rare.
What organism causes sporotrichosis?
Sporothrix schenkii
Basic stats of sporothrix schenckii
1) dimporhic fungus
2) yeast phase: cigar shaped cells. Grey white to tan colonies
3) mold phase: thin septate hyphae with delicate conidophores with pyriform conida. White colonies turn black with age
do dimorphic systemic mycoses grow fast or slow?
Disease characteristics for dimorphic fungal diseases
1) usual entry: respiratory. Inhalation of CONIDIA in the mold phase.
2) tissue phase: NOT TRANSMISSIBLE (so no person to person spread)
3) extent of disease related to cell mediated immune response of the host
Coccidiodes immitis characteristics
1) mold phase: barrel shaped arthrospores
2) yeast phase: large round spherules with many endospores
3) endemic to arid climates of the southwest
Valley Fever

1) immunocompetent hosts develop a flu like illness with high fever, chest pain, cough
2) accquired via inhalation of arthrospores from the mold phase
3) 60% asymptomatic
Diagnosis of coccidiodomycosis
coccidioides immits

1) demonstrate yeast spherules in tissue
2) cultivate the organism
Histoplasma capsulatum
1) mold phase: microconida and tuberculated macroconidia
2) yeast phase: small, lemon shaped INTRACELLULAR YEASTS inside of macrophages in LUNGS and RES
3) often found in sois enriched with BIRD FECES and BAT FECES
4) endemic in the Mississippi river vale; mexico and south america
Caused my histoplasma capsulatum

1) inhalation of microconida can lead to primary TB-like pulmonary disease
2) immunocompormised can develop progressive pulmonary disease or disseminated histoplasmosis
Diagnosis of histoplasmosis
1) demonstrate small lemon shaped yeast inside macrophage
2) look for tuberculated maacroconida when cultivated
3) serological testing
4) urinary antigen testing
Blastomyces dermatitidis

1) mold phase:
2) yeast: thick walled with BROAD BASED BUD
3) endemic to Mississippi AND OHIO river valeys and middle eastern seabord; Africa
Blastomyces disease
1) infection acquired by inhalation of microconidia
2) pprogressive pulmonary disease can occur (granulomas-->disseminated infection)
3) may infect PROSTATE
4) most COMMON form: chronic cutaneous and osseous disease
The three genera of dermatophytes:
1) epidermophyton
Overview of candida infections
1) major pathogen: Candida albicans
2) oval, 3-6 um yeast that reproduces by budding
3) yeast mey form pseudohyphae when budding is incomplete
Candida albicans infections/diseases
1) diaper rash, thrush, vaginitis, UTI, ocular, severe invasive disease
2) Disease usually superficial in immunocompetent hosts who had their microflora altered by antimicrobial therapy (vaginitis)
3) invasive disease: seen more in immunocomprimised. Most common cause of emias in UNC Hospitals in 2001.
4) most common cause of FUNGAL ENDOCARDITIS--susually seen in IV drug users or patients having valvular repir surgery. HIGH MORTALITY EVEN WITH TREATMENT.
Diagnosis of c. albicans
1) easy to recover candida; hard to determine what that means since it is resident microflora on body
Cryptococcus neoformans
1) the main pathogenic opportunistic fungus in humans
2) yeast that produces single or double buds. No psuedohyphae like candida
3) UNIQUE FEATURE: makes a polysaccharide CAPSULE that increases virulence.
4) found in PIGEON FECES, (unlike histoplasma, which is found in bird feces and bat feeces but NOT pigeon feces)
Cryptococcal disease
1) primary infection: usually pulmonary following yeasat inhalation. Usually subclinical and transitory
2) in aids patients, clinical signs appear. Cryptococcus skips the lungs and goes to the CNS
3) thus CRYPTOCOCCAL MENINGITIS is the most common form of nonbacterial meningitis in immunocompromised hosts
Diagnosis of cryptococcus neoformans
1) Sample CSF for organism
2) direcy exam with india ink prep of CSF
3) Latex Agglutination test: for presence of the capsular polysaccharid in CSF,irne, or serum.
Aspergillus characteristics
1) rapidly growing molds)
2) monomorphic (no yeast phase)
3) ubiqutious to most encironment
4) mycelia have septate, hyaline hyphae with distnctive conidia
Caused by aspergillus fumigatus

1) caused by inhaling conidia
2) disease depends on the host response:

A) ABPA: allergic pronchopulmonary aspergillosis: hypersensitive response to conidia, no tissue invasion. Seen in CF patients.

B) aspergilloma: fungus ball. Usually seen in patients with previous lung disease

C) Invasive pulmonary aspergillosis: parenchyymal invasion of growing fungus along vascular pathways

D) disseminated aspergillosis: involvemt of 2+ noncontiguous organ systems. Often fatal.
Diagnosis of aspergillosis
1) direct exam. Look for mold with septate hyphae with 45 degree dichotomous branchin
2) culture the rapidl growing hyaline mold
3) NEW TEST: measure the cell wall antigen GALACTOMANNAN in the bloodstream.
Therapy for aspergillosis
1) allergic disease=steroids
2) aspergilloma: resection
3) invasive disease: amphotericin B, azoles, etc.
1) ubiquitious organsims; often in bread mold
2) white, cottony mold grows rapidly; turns dark upon sporulation
3) large, ribbon like, non septate hyphae
Zygomycetes disease
(Zygomycosis or Mucormycosis)

2) presentations:

A) Rhinocerebral. Frequently fatal disease of KETOACIDOTIC DIABETICS. Causes infarc and necrosis.

B) thoracic: similar to invasive aspergilloisis. found in immunocompromised hosts.
Diagnosis of Zygomycetes
1) direct exam: broad, nonseptate hyphae with 90 degree branching
Pneumocystis carinii
1) found exclusively in HIGHLY IMMONOCOMPROMISED patients
2) fungus that has yeat to be cultured in vitro
3) has trophozoite (protozoan) form and cyst form
Pneumocystis carinii disease
Causes atympiical immnocompromised pneumonia

Shortness of breath, drug cough, fever

Disease incidene has dropped in HIV patients due to HAART.

Can disseminate to liver, spleen, kidney
Diagnosis of Pneumocystic carinii pneumonia

Priarily diagnosed on clinical presentation

You can do a direct fluoresent stain of induced sputum or specimines via lavage. (Broncoalveolar lavage: BAL)
Therapy for pneumoscystic carinii pneumonia
Trimethoprim sulfamethoxazole

HIV patients need prophylaxis if CD4 count goes under 200/uL.
Cyptococcus neoformans key points
Yeast that produces polysaccharide capsule

Major fungal cause of meningitis

Capsular polysaccharide antigen is easily detected in serum and CSF by latex agglutination
Aspergillus sp. key points
Molds that make septate hyphae with 45 degree branching

Invasive disease in IC hosts has high mortality
Zgomycetes key points
Can cause rapidly fatal infections in immunosuppressed diabetic patients

Hyphae are characterized as broad, aseptate hpyhee with 90 degree branching
Pneumocystis key points
cause of atypical pneumonia in IC patients

Treat with trimethoprim/sulfamethxazole (also used for prophylaxis in CD4 under 200 HIV patients)
Shape names: sphere
curved rod
spirillum or spirochete
multiple shapes
Six types of human pathogen
What is bacterial cell wall made of?
Peptidoglycan (murein): linear repeating disacchharide unit is crossliked by short peptides.

Found in all bacteria EXCEPT MYCOPLASMA

Degraded by lysosyme, autolysins
Gram positive cell wall
1) 40 layers of peptidoglycan
2) contains Teichoic acid that is linked to the sugar backbone of the PG
3) also contains lipoteichoic acid, which runs through the PG layer but is linked to the outer lipid leaflet of the plasma membrane
Gram negative Cell envelope
1) much thinner PG cell wall
2) LIPOPROTEIN links PG to louter membrane
3) periplasmic space between inner and outer membranes contains the thin cell wall and lipoprotein linkers to the outer membrane
4) outer leaflet of outer membrane contains LPS
Structure of LPS
1) Lipid A (classic edotoxin)
2) core polysacharide
4) optional repeat unit)

(indide to out)
WHich type of bacteria are usually more AB resistant and why?
Gram negative. Beacsue of the additional membrane, that adds more protection against hydrophilic molecules.
S layer
Surface layer of a single protein arranged in a regular crystalline array. Protects against phagocytosis and complement
=irregular cluster
chains of cells
PG synthesis
1) PG made of NAG-NAM repeats crosslinked by peptide.
2) Firsf NAG-NAM pade, and pentapeptides (with 2 terminal D-Ala) are attached to NAM
3) crosslinking: terminal D-Ala cleaved from a NAM-pentapeptide
4) then the new terminal D-Ala is attached to an adgacent NAG-NAM's pentapepdie, and a crosslink is formed.
Cell wall synthesis interferers
1) D cyclosereine: inhibits synthesis of D-Ala needed for peptides
2) vancomycin: blocks cross linking by binding to D-Ala D Ala precursurs
3) Bacitracin: blocks regeneration of carrier used to make NAG-NAM polymers
4) B-lactams: block transpeptidation rxn used to crosslink. Acts ONYL on growing cells to block PG formation
1) beta lactam.
2) side chains can be modified to alter activity by increasing resistance to beta lactamases or increasing entry into cell
1) beta lactam.
2) usually beta-lactamase resistant
New beta lactams
1) broader spectrum
2) more sensitivity
3) more activity against gram neg; at expense of gram pos activity
Genotypic resistance to pen
1) mutation of PBPs
2) cleavage of b-lactam ring (b-lactamas)
3) mutations that prevent entry through porins
genotypic resistance to vancomycin
Occurs in a way not thought possible: D-ala-d-ala substituted by d-ala-d-lactate. Major clinical problem. So things that bind d-ala-d-ala don't work.
Antagonism between grugs
Pen is a cidal that works only on growing cells. Any dru that is static and slows/stops growths makes pen less effective.
How does vancomycin work?
binds d-ala-d-ala, preventing cross linking
List of ribosomal inhibitors
1) aminoglycosides, aminocyciltos (streptomycin, kanamycin, gentamicin, tobramycin)

2) tetracyclines

3) Macrolides (eerythromycin, clindamycin, azythromycin)

4) Oxazolidinones
1) ex: streptomycin, kanamycin, gentamicin
2) bind to 30S subunit proteins
3) cause misreading of code
4) cidal
1) act on 30S ribosome
2) generally static
3) resistance via 30S alteration (rare), plasma-encoded system for decresed uptake
1) Ex: erythromycin, clindamycin, azithromysin
2) act on 50S ribosome
3) block peptidyl transfer/transolcation
4) static
5) resistance: plasma encoded methylase decreases binding to 50S
1) limited use for resistant enterococcal/staphylococcal infections
2) only works on gram positive
3) interferes with translocation on ribosome
Lists of nucleic acid metabolism inhibitors
1) sulfonamides
2) Trimethoprim
3) rifamycins
4) Quinolones
5) novobicin
1) Inhibits incorporation of PABA into folic acid; they die because they hve little free purines and pyrimidines
1) inhibits DHF reductase
2) sinergistic with sulfonamides
3) basically inhibits an additional step in NA syntheisis

1) binds to RNA pol, blocking tanscription in bacteria , myco, some fungi. But rapid mutation of target site can occur.
DNA gyrase inhibitors
1) quinolone
2) novobysin
Reduces supercoiling, etc...
A fluorinatted quinolone (gyrase inhibitor--blocks rejoining after cleavage): very broad spectum. Relative lack of toxicity
Penicillin synergy
Often synergistic with aminoglycosides: increses entry of aminoglycosides to intracellular target.
What is conjugation chiefly responsible for?
Rapid spread of multiple AB resistance through populations fo Gram negative bacteria
Conjuation in gram neg v. gram pos
Gram neg: usually involves sex pilus
Gram pos: no sex pilus. Pheremones may induce aggregate formation between cells
Transduction: generalized v. specialized
Transuduction: DNA transfer mediated by bacteriophage.

Generalized: any gene has a chance
Specialized: only a designated region is tranferred
What is a biofilm?
Assemblage of microbial cells growing on a surface and encased in an extracellular polysaccharide matrix
Otitis media and biofilms
1) most aeffusines from acute OM are culture positive
2) but most effusions from chronic recurrent OM are culure negative.
3) so: most chromic OME is probably due to biofilm growth
Pseudomonas aeruginosa biofilms
1) CF patients are often colonized with p. aeruginosa biofilm (p.a. embedded in elginate matrix)
2) Antibody response not able to penetrate bioofilm. More antibody that is made, worse the clinical outcome.
3) so you often try to immune supress CF patients
4) Antibiotic treatment probably only kills planktonic cells
Biofilm strategies
1) use AB coated catheters
2) ID new drig targets, including factors that cause switch from planktonic to biofilm growth
Process of septic shock syndrome
1) LPS binds to CD14, via help from LPB (lipid binding protein)
2) This binding causes activation (somehow) of TLR4 (on macrophage, monocyte, neutrophil, endothelial, dendritic cells), which recognizes PAMPs
3) TLR4 bindin eventually increases activity of NF-kB
4) NF-kB is a transcriptional activato r of a lot of cytokines that cause inflammatory response. Synergistic loops start
5) TLR4 binding also causes activation of adaptive response
6) other toll receptors bind other toxins
OTher mediators of Lipid A mediated shock
1) Prostaglandins: cause fever
2) NO: cause vasodilation
3) clotting cascade activation/vascular ddamage
4) (ACTIVATED PROTEIN C prevents clotting and blocks inflammatory cytokines)
What is the first molecular therapeutic approved for human use in sepsis?
Activated protein C
Clinical presentation of shock
1) CO up
2) TPR down (warm pink shock)--early septic shock!
3) organ damage (Systemic Inflammatory Response Syndrome)
4) WBC up
Interruptoin of shock
1) fill the tank with fluid
2) drain pus
3) dont use ABs that break up bugs and release more Lipid A/PG frags
4) Lipid-A antiboddies have failed
Can you have gram positive shock?

1) PG or lipoteichoic acids can activatae TLR2 on cacrophages
What is TLR 9 activated by?
Microbial DNA
What anaerobes cause brain abscesses?
What anaerobe casues device-related meningitis?
Ludwigs angina
Deep fascial space infection of the head and neck

Rapidly progressive cellulitis of teh submandibular and sublingual spaces; can compromise airway
Retropharyngeal space infecction
Bulging of posterior pharyngeal wall occurs. can cause asphyxiation.
What can cause deep fascial space infections
Oral anaerobes:

"Lumpy jaw"

Associated with dental procedures
Sulfur granules bay drain from the sinus tract
Lung abscesses
KEY SIGN: "fetid breath:, excessive EtOH use

Follows aspiration

Orgs cove from oral cavity:

Follows trauma to gI tract
Can lead to bacteremia and abscess formation

Frequently found:
Bacteroides fragilis (b-lactamase makers!)
E. coli
Peptostreptococcus and prevotella (sometimes)
BV candidates
Sometimes B. fragilis
What is a good sign for diagnosis of anaerobic infection?
Mixture of gram pos and gram neg in an area you would find anaerobes
Clostriduim shape?
Boxcar shaped, large G+ rod
Therapy for anaerobic infections
1) drain abscess
2) Metronidazole: usually effective. Not active against aerobes.
3) Use combo beta lactamase inibitor and penicillin
Why do aminoglycosides not work on anaerobes?
doesn't work unless Oxidative metabolism is occuring!
General characteristics of clostridium
1) gram pos rod
2) boxcar shaped
3) anaerobic, spore former
4) lives naturally in soil
5) fast grower
Clostridium divicile epidemiology
1) causes nosocomial diarrhea
2) usually seen after antimicrobial therapy that alters gut flora
3) spores can survive for months
C. dificile pathogenicity
1) makes 2 toxins: A (enterotoxin), B (cytotoxin)

Can make eithe both or neither; usually not just one
Clinical disease with C. dificile
1) Org picked up into gut
2) gut flora altered by antimicrobial terapy
3) alteration reduces gut inhibition of c. difficile
4) grows and makes toxin that mediates diarrhea
Diagnosis of c. dificile
1) culture not useful due to high carriage rate
2) toxin detection is optimal method
Treating c. difficile
1) Metrodiazodole r vancomycin
C. perfringens
1) soil org, also found NORMALLY in gut
2) introduced by trauma
3) causes GAS GANGRENE
4) also causs FOOD POISONING
clinical presentation of c. perfringens
1) infection seen 1-4 days post trauma
2) sudden , persistent, sever pain in trauma region
3) area of trauma red-->bronze
4) low fever
5) tachy
6) may get hemolytic anemia, hypotenion, renal failure
Diagnosis of c. perfringens
1) many boxcar shaped G-pos rods
2) characteristic DOUBLE ZONE of hemolysis on sheep blood agar
3 kinds of botulism
1) infant botulism. Source is environment, honey

2) food borne. Ingestion of improperly canned veetables (spores withstand boiling)

3) would botulism. unusual
Pathogenesis of c. botulinim
1) bug makes POTENT NEUROTOXIN (eight types)
2) toxin is ingested (food borne) or produced (infant/wound)
3) toxin binds to presynaptic membrane and blocks ACh release. Causes flaccid paralysis.
4) dath due to respiratory paralysis
Pathogenicity process of c. tetani
1) wound
2) tetanus toxin made in wound
3) toxin binds at NMJ
4) toxin transfers to other neurons
5) blocks post-synaptic inhibition leading to hyper-excitibility
Clinical manifestation of tetanus
1) vague complaints of weaknes
2) lockjaw/trismus
3) interference with respiration
General facts on clostridiun
Anaerobic, spore forming gram positive bacilli
Why is their often relapse of c. dificile diarrhea?
Inability of antimicrobials to kill spores
Pseudomonas aeruginosa
Major nosocomial pathogen

1) ox pos, glu non fermenting
3) produces distinctive blue green pigment (pyocyanin)
4) widely resistant to antimicrobials
What is the most common nosocomial infection?
VAP: ventilator associated pneumonia.

When caused by p. aeruginosa, it has a high M&M
P. auerginosa and CF
Unusual morphotype seen exclusively here: MUCOID

Planktonic growth-->biofilms.

mucoid growth triggers intens e immune response that overwhems protease inhibitors that normall protect the lung from scell damage.

Almost impossible to eradicate this
What is the most common cause of gram neg nosocomial bacteremia?
what does b. pertussis grow on?
Speciatly agar only: ("Bordet-Gengou" medium)
gram pos diplococci...
Strep pneumoniae
For which bugs do you use serologic tests?

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