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STI Pathogens: Pathogen Chlamydia trachomatis General Characteristics Obligate intracellular bacteria: but NOT an energy parasite (has own ATP transportersonly requires host ATP for persistent infection) Cell wall similar to G(-): but lacks peptidoglycan Affects more females than males Conditions Caused Often asymptomatic Serotypes D-K cause urogenital infection: Females: -Cervicitis -Salpingitis (lead to PID) -Urethritis -Chronic pelvic pain Males: -Urethritis -Epididymitis Neonates: -Conjunctivitis -Pneumonia Virulence Factors Developmental Cycle: Elementary Body: infectious, enters cells and is enclosed in vacuole (resist fusion with lysosome) Reticulate Body: non-infectious and metabolically active; replicated in vacuoles to form inclusion bodies -Inclusions derived from more than 1 EB fuse in the cell to form a single inclusion -Mutations (ie. in lnc gene) can prevent fusion Serotypes L1-L3 cause Lymphogranuloma Venereum (LGV): -Increases risk for HIV coinfection -Treat the same way as Chlamydia -No good treatment for systemic infection Neisseria gonorrhoeae Non-motile, G(-), diplococcic Facultative intracellular bacterium: replicates in PMNs and subepithelial tissue; humans are the only host Fastidious growth requirements: -Inhibited by FAs -CAP or Thayer-Martin plates -37 degrees, CO2 enriched Affects roughly equal amounts of men and women Infections facilitate transmission of chlamydia and HIV: assume chlamydial co-infection and treat for it Males: -Urethritis (most common) -Epididymitis Females: -Cervicitis (most common) -Progress to PID Disseminated Infection: rare -Bacteremia -Arthritis, dermatitis, endocarditis Pili: -Function:colonization -Phase varation: expression vs. non-expression -Antigenic variation: change pilus subunit expressed Opa proteins: -Function: close contact after pili bind and anchor -Phase variation: expression (opaque colonies) vs. nonexpression -Constitutively transcribed: but translation controlled by CTCTT frameshifts Pathogenesis Disease sequelae due to inflammatory response Disseminates from primary site of infection: in mononuclear cells Can become persistent: organism present and viable but not culturable -Reduced expression of MOMP -Increased expression of stress proteins (hsp60, hsp10) and LPS (chronic inflammation) -May be induced by IFN-γ or the use of penicillin LGV: -Local: small papule on external genitalia/anus, swollen LN, mucoid anal discharge -Systemic: fever, rashes, nausea (possibly meningitis or arthritis) -Can become serious chronic/systemic disease Adherence: to mucosal surface following sexual contact Invasion: can invade epithelial cells, but do not always Mucosal Damage: due to granulocyte response Clinical ID Epithelial cells from infected site -Scrapings -First-catch urine -Pus from genital lesions (LGV only) Direct Detection: -Fluorescent Abs to MOMP or LPS -PCR -Ligase chain reaction (LCR) -Multiplex reactions (detect multiple STIs) Direct Gram Smear: -Only sensitive for symptomatic men Culture: -Diplococci within PMN diagnostic Oxidase (+) Direct Detection: -Enzyme immunoassays -DNA/RNA hybridization -Multiplex PCR to detect chlamydia as well LOS: -Structure: lipid A w/o O Ag -Variation: sialyation confers serum resistance (dissemination) -Proinflammatory OMP1: used for serotyping -Porin IgA Protease: -Cleaves IgA1 (secretory and non-secretory) -Adherence in presence of IgA -Loss of protease does not affect infectivity Treponema pallidum (Syphilis) Obligate human pathogen G(-) spirochete Outer glycosaminoglycan coating Very motile (corkscrew) Difficult to culture and does not stain by routine methods Highly unstable: rapid death in environment and high sensitivity to antimicrobials Metabolically crippled organism Infects more men than women Chancres increase susceptibility to HIV transmission Transferrin: iron acquisition -Loss DOES cause loss of infectivity Very little is known about the organism Primary Syphilis: chancre development 3-4 weeks after contact on external genitalia -Filled with bacteria -Hard, red, painless Hyaluronidase: invasion Secondary Syphilis: fever, sore throat, rash (palms/soles/face) -After primary lesion has healed -Filled with bacteria -Some resolve via immune response, others go latent Tpr (repeat genes): invasion Latent Syphilis: seroreactive but no signs or symptoms -Variable length -Can progress to tertiary symptoms if untreated or unresolved Tertiary Syphilis: granulomatous gummas on the skin (due to host immune response) -No bacteria in gummas Outer membrane: few integral proteins (helps evade immune system) Transmission: -Direct sexual contact with an individual with active primary or secondary lesion -Transplacental Causes disease of blood vessels and perivascular area: invades mucus membranes, multiples rapidly, and spreads to systemic circulation BEFORE development of primary lesion Darkfield microscopy: fluid from primary and secondary lesions Serological: VDRL/RPR: non-specific -Positive during primary and secondary stages -Reduction indicates successful treatment -Many false + Treponemal Tests: -FTA-Abs: detects Ab specific to T.pallidum (present for life, so can’t be used to detect successful treatment) -NERA-TP: microhemagglutination test Genetic Probes: PCR (soon) Congenital: anti-treponemal IgM diagnostic (IgM does not cross placenta- must be from fetus) Neurosyphilis: tabes dorsals, seizures, dementia, NF tangles post-mortem CV Syphilis: commonly aortic aneurysm Haemophilus ducreyi (Chancroid) Candida albicans (Vulvovaginal Yeast Infection) Fastidious G(-) rod Strict human pathogen Not really classified as an STI! Fungi that is normal flora: GI tract, mucuocutaneous sites (vagina, mouth) Congenital Syphilis: fetus susceptible at ANY time during gestation -Often asymptomatic at birth -Progresses to rhinitis, pneumonia and failure to thrive -Can be fatal if severe Increases susceptibility to HIV: due to chancroids Chancroids: painful, genital ulcers with ragged edges Most common cause of vulvovaginal yeast infections Predisposing Factors: -Pregnancy -Diabetes -Oral contraceptives/hormones -Antibacterial Abx Recurrent Infections: can be caused even in healthy women -Macrophage dysfunction? Trichomonas vaginalis (Trichomoniasis) Highly motile, flagellated protozoan (parasite) No cyst form: but can survive in moist environments Most common STI worldwide Men: generally asymptomatic Women: dysuria, vaginal itching and burning -Severe infections produce foamy, yellow green discharge -- Multiple Forms: hyphae (tissue invasion) and yeast (pathogenic form in the body) Adhesins: can bind fibronectin, collagen, laminin Invasion: proteases and phospholipases produced by hyphal form Can infect abraded skin, mucosal surface and stratified squamous epithelium: chancroids 214 days later Infection requires: -Increase in local numbers of candida -Compromised integrity of epithelial surface Antibody based detection DNA probes Multiplex PCR -White-gray pseudomembrane on vaginal mucosa -Yellow-white discharge -Hyphal forms seen in vaginal scrapings Normal immune response: phagocytosis by macrophages (bind mannan wall) Biofilm formation: assists in pathogenesis SAPs: proteinases only found in pathogenic yeast; pH regulated activity -Determines level of tissue invasion -Regulates other VFs Coated with host-derived macromolecules: evasion? -α1 antitrypsin, fibrontectin, α2macroglobulin, lipids Phagocytosis: of bacteria, virus, RBC, PMNs Upsets Flora: ingest lactobacilli Persistence: up to 90 days; worse during menses and pregnancy Transmission: sexual contact (most often) PMN inflammatory response: cell destruction -Microscopic examinations of wet mount preparations (vaginal or urethra discharge) -Culture of urogenital specimens