1. MICR 201 Microbiology for Health Related Sciences
Lecture 18: Microbial diseases of the urinary and reproductive system
Edith Porter, M.D.
MICR 201 Microbiology for Health Related Sciences

2. Lecture outline
Structure & function and normal microbiota of the urinary and reproductive system
Ports of entry
Diseases of the urinary system
Bacterial
Diseases of the reproductive system
Viral
Fungal
Protozoan
TORCH

3. Female urinary system

4. Female reproductive organs
Note the short urethra and proximity to anus

5. Male urinary and reproductive organs

6. Normal microbiota
Urinary bladder and upper urinary and reproductive tract sterile
Urethral opening colonized with skin flora (mainly gram+ bacteria) and in men, Mycobacterium smegmatis
Lactobacilli predominant in the vagina
Urine is normally sterile but can be contaminated by the microbiota of the urethral opening

7. Ports of entry for microbial diseases of the urinary and reproductive systems
Microbes usually enter the urinary system through the urethra
Microbes usually enter the reproductive system through the vagina (females) or urethra (males)

8. Cystitis Urinary bladder infection
Dysuria: difficult, painful and imperative urination
Usually caused by
E. coli
S. saprophyticus (in female)
May also be caused by
Associated with kidney stones: Proteus
Nosocomial: Klebsiella, Pseudomonas, Enterococcus faecalis
Antibiotic-sensitivity tests should guide treatment

9. Diagnosis of cystitis
Clean catch urine (midstream urine after urethral opening had been cleansed)
Refrigerate until urine is processed, because there is typically some contaminating normal flora present (< 10,000/ml)
In general > 100,000 bacteria/ml = infection
Single organism

10. Pyelonephritis If cystitis left untreated pyelonephritis may follow
Fever, flank or back pain
75% caused by E. coli
In the elderly danger of sepsis
i.v. antibiotics
Diseased kidney
Normal kidney

11. Sexually transmitted infections (STIs)
Major public health impact
In the US ~15 Mio new cases/year (or ~30 new infections /min)
Female often without major symptoms
Major cause of infertility
Prevented by (properly used) condoms and vaccination (genital warts)

12. Most common causes of STI
Most common bacterial STIs
Neisseria gonorrhoeae (gonorrhoea)
Chlamydia trachomatis (non-gonococcocal urethritis, NGU)
Treponema pallidum (Syphilis)
Treated with antibiotics
Most common viral STIs
Herpes simplex 2 (genital herpes)
Papilloma virus (genital warts, cervical cancer)
Other STIs
Fungal: candidiasis
Protozoan: trichomonas

13. Neisseria gonorrhoeae
Gram negative diplococci
Attaches to columnar epithelial cells via pili
Oropharyngeal, eyes, rectum, urethra, opening of cervix, external genitals of pre-pubertal females
Antigenic variation of pilin and expression of opa which blocks T cells and immunological memory
Typically urethritis, cervicitis
Females may be asymptomatic; males have painful urination and pus discharge
Old disease (name coined in A.D. 150 “flow of semen”)
In rare untreated cases systemic spread and joint infection
Arthritis (one knee joint only)
Upon birth
Ophthalmia neonatorum

14. Gonorrhea: discharge and pus
Neutrophil

15. Incidence and geographical distribution of gonorrhoea

16. CDC: 2009 statistics

17. Nongonococcal urethritis
Chlamydia trachomatis
May be transmitted to newborn's eyes
Painful urination and watery discharge
Mycoplasma hominis
Ureaplasma urealyticum
Watery discharge in CT

18. Chlamydia trachomatis
Infects epithelial cells
Special life cycle with 2 life forms
Elementary body, resistant and infectious
Reticulate body, sensitive and proliferating
Infection must be treated through 2 life cycles of CT

19. The two life forms of Chlamydia
48 h -72 h

20. Pathogenic factors of C. trachomatis
Contribute to intracellular survival and proliferation
In part secreted via Type III secretion apparatus
Effect actin rearrangement and endocytic uptake of CT
CT inserts proteins in inclusion (endosome) membrane that prevent fusion of host lysosomes
CT releases proteins into the cytoplasma that interfere with NFkB signal transduction, a key pathway of the acute inflammatory and innate immune response

21. Pelvic inflammatory disease
N. gonorrhoeae
C. trachomatis
Scarring can block uterine tubes
Chronic abdominal pain
Infertility and ectopic pregnancies
Laparascopic image showing acute inflammation of right tube, fimbriae and ovaries

22. Diagnosis of gonorrhoea andNGU
Nulceic acid amplification tests most accurate
PCR based
Antigen detection (ELISA)
Culture (gonorrhoea > NGU)

23. Syphilis Treponema pallidum, gram negative spirochete
Invades mucosa or enters through skin breaks

24. Three stages of syphilis
1. stage: acute ulcer (painless, hard), highly infectious
2. stage: systemic spread into skin, highly infectious
3. stage: gumma, immunological response in tissue, neurosyphilis,

25. Diagnosis of syphilis Direct diagnosis: Indirect serological diagnosis
Darkfield microscopic identification of bacteria
Staining with fluorescent-labeled, monoclonal antibodies
Indirect serological diagnosis
Reagins: antibodies against conserved structures on Treponema
Specific antibodies

26. Genital herpes Herpes simplex virus 2 (Human herpesvirus 2 or HHV 2)
Burning sensation followed by development of fluid filled vesicles
Sometimes non-symptomatic
Neonatal herpes transmitted to fetus or newborn
Spontaneous abortion of severe fetal damage
Virus enters latency with recurrence

27. Genital herpes: recurrent, very painful vesicles
“Unlike love herpes is forever”

28. Genital warts Human papillomaviruses
HPV 16 causes cervical cancer and cancer of the penis
DNA test to detect cancer-causing strains
Vaccination against HPV strains

29. Candidiasis Candida albicans
Severe itching and thick yellow cheesy discharge
Result from opportunistic overgrowth
Increased during pregnancy and in diabetic women

30. Trichomoniasis Trichomonas vaginalis Protozoan
Found in semen or urine of male carriers
Vaginal infection causes irritation and profuse discharge (foul smelling, frothy)
Diagnosis by microscopic identification of protozoan

31. Intrauterine Infections: TORCH
Toxoplasma
Other
Treponema pallidum
Listeria monocytogenes
Rubella
Cytomegalovirus
Herpes simplex

32. Important to remember
Urethra opening (gram+ bacteria, Mycobacterium smegmatis) and vagina (Lactobacillus spec.) are populated by normal microbiota.
The female urethra is much shorter than the male. This and close vicinity to anus makes women more prone for urinary tract infections.
Diseases of the urinary system are mainly of bacterial origin. In out patients: E. coli, S. saprophyticus; associated with kidney stones: Proteus; noscomial: Enterococcus faecalis, Klebsiella, Enterobacter, Pseudomonas.
Females often have less symptoms than men during an STI.
Infertility is a frequent complication after STI.
Diseases of the reproductive system of bacterial origin: Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum; of viral: Herpes simplex 2, Papilloma virus; of fungal: Candida albicans; of protozoan: Trichomonas vaginalis
Birth defects are in particular associated with TORCH (Toxoplasma, Rubella , Cytomegalovirus, Herpes simplex).

33. Check your understanding
1) Cystitis is most often caused by A) Escherichia coli. B) Leptospira interrogans. C) Candida albicans. D) Neisseria gonorrhoeae. E) Pseudomonas aeruginosa. 2) Which of the following is often diagnosed by detection of antibodies against the causative agent? A) Nongonococcal urethritis B) Gonorrhea C) Syphilis D) Cystitis E) Candidiasis 3) Normal microbiota of the adult vagina consist primarily of A) Lactobacillus. B) Streptococcus. C) Mycobacterium. D) Neisseria. E) Candida.