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

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

Female urinary system

Female reproductive organs Note the short urethra and proximity to anus

Male urinary and reproductive organs

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

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)

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

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

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

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)

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

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

Gonorrhea: discharge and pus Neutrophil

Incidence and geographical distribution of gonorrhoea

CDC: 2009 statistics

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

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

The two life forms of Chlamydia 48 h -72 h

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

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

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

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

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,

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

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

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

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

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

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

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

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).

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.