Microbiology of the Vagina and Penis - Skildum

Question 1

What does the normal microbial communities of the vagina consist of?

Answer 1

In ~80% of healthy women, lactobacilli are the dominant microorganisms.

Lactobacilli are gram positive rods/bacilli, facultative anaerobes

*Lactobacilli iners, *L. gasseri, L. cripsatus and L. jensenii are the most common.

Question 2

What are the three products of Lactobacilli that help maintain the microbiota of the vagina?

Answer 2

1. Lactic acid: through anaerobic fermentation, decreases pH (lactic acid makes environment more hostile to other pathogens, lactate is substrate for immune system)
2. Hydrogen peroxide; hydroxyl radicals (makes hostile environment)
3. Bacteriocins proteins that depolarize pathogenic bacteria => kill bacteria

Question 3

What does the vaginal microbial community depend on for maintaining healthy colonies of Lactobacilli?

Answer 3

Estrogen!

Estrogen causes vaginal epithelial expansion => vaginal epithelial glycogen production => epithelial cell sloughing => extracellular glycogen converted to glucose => Glucose taken up by lactobacilli

Question 4

Why do pre-pubertal and post-menopausal women have different microbial communities with less robust pathogen defense activity?

Answer 4

decreased estrogen production

less glucose for lactobacilli to utilize

Question 5

What are the two ways (enzymes) Lactobacilli can utilize to make hydrogen peroxide?

Answer 5

1. From pyruvate via Pyruvate oxidase (requires oxygen)

2. From glucose via Glucose oxidase

Question 6

Hydrogen peroxide does not inhibit the growth of what common vaginal pathogen?

Answer 6

Gardnerella vaginosis

Question 7

What are Bacteriocins? Primary fxn?

Answer 7

proteins produced by bacteria that are lethal to other bacteria

***Bacteriocins form a pore in the target cell’s membrane, resulting in depolarization and outflow of cytoplasmic contents.

Question 8

Which molecule has an inhibitory effect on other pro-inflammatory cytokines?

Answer 8

IL-10

Question 9

What receptors recognize common molecular patterns in pathogens and mediate inate immune response such as cytokine and chemokine production?

A. Major Histocompatibility Complex I (MHC I)
B. Major Histocompatibility Complex II (MHC II)
C. T Cell receptors
D. Toll Like Receptors (TLR)

Answer 9

D. Toll Like Receptors (TLR)

Question 10

Which pathogen is least likely to be sensitive to ceftriaxone?

A. Escherischia coli
B. Mycoplasma genitalium 
C. Neisseria gonorrheae
D. Staphylococcus aureus
E. Streptococcus pyogenes

Answer 10

B. Mycoplasma genitalium => has no cell wall

Ceftriaxone = cell wall inhibitor

Question 11

After a bacteria is phagocytosed and digested by a macrophage, how are its antigens presented to cells of the immune system?

A. Between Va and Vb domains of the T cell receptor
B. On the B cell receptor (IgM)
C. On MHC I
D. On MHC II
E. On CD4

Answer 11

D. On MHC II

Question 12

Bacteria are more harmful if they carry genomic pathogenicity islands, which often encode toxins. Transfer of the Staphylococcus aureus SAPI1 pathogenicity island depends on _______________.

A. Conjugation
B. Mutation
C. Transduction
D. Transformation

Answer 12

C. Transduction

Question 13

What is different about the non-dominant lactobacilli microbiotos of healthy females?

Answer 13

pH slightly higher more basic (5.3 – 5.5)

Question 14

What causes bacterial vaginosis?

Answer 14

Not caused by a single pathogen!!!!

***It is a DISRUPTION of the normal vaginal microflora!

Question 15

What type of bacteria is typically most abundant in BV patients?

Answer 15

Gardnerella vaginalis

Question 16

BV is associated with increasing concentrations of what bacteria?

Answer 16

Anaerobic:
***Gardnerella vaginalis (gram variable, facultative anaerobic bacilli)

Mycoplasma hominis (tiny, lack a cell wall, require cholesterol in growth media)

Mobiluncus sp.  (gram negative, anaerobic, motile curved rod)

Atopobium vaginae (gram positive, anaerobic, elliptical cocci or rod shaped)

Question 17

How does Metronidazole treat bacterial vaginosis?

Answer 17

Metronidazole can only be reduced to its active form in anaerobic organisms.

Once active it:

1) Interferes with bacteria’s fuel metabolism
2) Generates reactive nitrogen, damaging nucleic acids

Question 18

What damage does PID cause in the upper reproductive tract?

Answer 18

selective loss of ciliated epithelial cells in the fallopian tube

can result in infertility or ectopic pregnancy

Question 19

What does the microscopic examination of vaginal samples show in PID?

Answer 19

Clue cells

Question 20

What pathogens cause PID?

Answer 20

Most common: Neisseria gonorrhoeae
(gram negative diplococci, non-motile, not acid fast, oxidase positive)

Most common: Chlamydia trachomatis
(gram negative, obligate intracellular parasite)

Haemophilus influenza - often accompany Neisseria and Chlamydia
(gram negative coccobacilli)

Streptococcus pyogenes - often accompany Neisseria and Chlamydia
(gram positive chained cocci, facultative anaerobic)

Rare causes: Streptococcus pneumonia, Escherischia coli, Klebsiella sp., Proteus mirabilis

Emerging cause: Mycoplasma genitalium
(tiny, lack a cell wall, require cholesterol in growth media)

Question 21

What is the treatment for PID?

Answer 21

Ceftriaxone (or Cefoxitin): Cephalosporin derivatives that binds penicillin binding proteins and inhibits bacterial cell wall synthesis, resulting in osmotic imbalance and death of dividing cells. It is effective against bacteria that produce b-lactamase.

Doxycycline: Binds to bacteria’s 30S ribosome and prevents tRNA binding, preventing protein synthesis.

+/- Metronidazole: Action require a redox reaction only possible in anaerobes.

Question 22

What signs/symptoms characterize Toxic shock syndrome (TSS)?

Answer 22

fever
diffuse rash
hypotension
organ dysfunction: renal, hepatic, muscle, etc.

Question 23

90% of TSS cases are associated with what pathogen?

Answer 23

Staphyloccus aureus

Strep pyogenes accounts for the rest

Question 24

What is the pathogenesis of TSS?

Answer 24

Superantigens produced by bacteria bind both TCR and MHC II, creating an immunological synapse without any specific antigen.

This causes systemic activation of T cells regardless of the specificity of their TCR.

Th1 response: IL-2 and IFNg + Macrophage response: IL-1 and TNF

Question 25

How does Staph aureus produce the Superantigen in TSS?

Answer 25

TSST-1 is encoded on the SaPI1 pathogenicity island spread by phage transduction.

Thus a community of S. aureus that is in benign equilibrium with the vaginal microbiome can become pathologic quickly if SaPI1 spreads through the community.

Question 26

Do patients with Toxic Shock Syndrome have positive S. aureus blood cultures?

Answer 26

Rarely

Question 27

Do patients with S. aureus sepsis (bacteria present in blood) get Toxic Shock Syndrome?

Answer 27

Rarely

Question 28

What does the normal microbiome of the penis consist of?

Answer 28

The penis microbiome in healthy males is similar to the vaginal microbiome in healthy reproductive age women: dominated by lactobacillus.

Question 29

What may be a consequence of having reduced Lactobacillus in the penis microbiome?

Answer 29

Infection

Infection with an STI is associated with a depletion of lactobacillus.

Question 30

What effect does circumcision have on HIV-1 transmission?

Answer 30

Decreased potential for HIV-1 transmission

Circumcission => alters microbiome/macrophages further from surface => less chance of HIV

Question 31

How does circumcision shifting the normal microbial community towards aerobic bacteria help prevent infection?

Answer 31

reduces inflammation and reduces the number of CD4+/CCR5+ macrophages in the urethra

Question 32

What are the common causes of Epididymitis in Prepubertal boys, men 35?

Answer 32

Prepubertal boys: Escherichia coli

Men younger than 35 years: Chlamydia trachomatis, Neisseria gonorrheae

Men 35 years and older: E coli, Pseudomonas species

Question 33

What does the normal microbiome of the prostate consist of?

Answer 33

Trick question!

It is not known whether there is a ‘prostate microbiome’ or ‘normal prostate microflora’.