醫(yī)學微生物學資料：Neisseria

1、Neisseria Neisseria meningitidis Nerrseria gonorrhoea1Neisseria : general features Gram-negative diplococci are bean-shaped Gonococci are more fastidious than meningococci All Neisseria are oxidase-positive Similar pili and OMPsVarient of LPS:2Neisseria species Bacteriologic and Pathogenic Features

2、of Neisseria Antigenic structure Growth Outer membrane proteins Organism Blood agarML agaraCapsule Pili Adherence associated Porins Blocking AB-associated bTransmission DiseaseN meningitides +Polysaccharide （12 serogroupsc)Class I, II antigenically diverseClass 5 (4 variants )PorA PorBeClass 4Inhala

3、tion of respiratory droplets Meningitis N gonorrhoeae _+None Antigenically diversed Protein II or Opa (12variants)PorA PorBProtein III Sexual contact of mucosal surfaces Urethritis, cervicitis , PID Other Neisseria species +_None Present Unknown Unknown Absent Normal respiratory flora None 3Meningoc

4、occi & Gonococci4DNA homology :70%Meningococci GonococciPolysaccharide capsules+-plasmids-+Infection Upper respiratory tract infectionGenital infection Meningococcal disease Epidemiology Nasopharyngeal carrier rate is 10% Spreading is by respiratory droplets B,C, and Y are the most common serogroups

5、Group A strains can cause widespread epidemics 5Pathogenesis Meningococci range from carrier state to bacteremia Pili attach to microvilli as prelude to invasion 6Proteins scavenge iron from transferrin Polysaccharide capsule are antiphagocytic LOS+ sialic acid interferes with complement deposition

6、Spread to blood and CNS produce systemic endotoxemiaLPS and peptidoglycan trigger cytokine releasePathogenesis 7Immunity Group-specific anticapsular antibody is protectiveComplement component deficiencies enhance risk Most common age of infection is 6-24 monthsAbsence of antibody correlates with sus

7、ceptibility Infection, carrier state, or other polysaccharides may stimulate antibody T-cell-independent mechanisms are involved 8Immunity to the meingococcus 9Meningococcal disease: clinical aspects Manifestations Acute purulent meningitisMeningococcemia and rash may progress to DIC Systemic featur

8、es resemble endotoxic shock DiagnosisDirect CSF Gram smears are diagnostic Culture requires only blood agar.10Treatment and preventionTreatment Penicillin ceftriaxone and cefotaxime Prevention Chemoprophylaxis ：RifampinClose contact with case is indication for prophylaxis MCV4 vaccine stimulates T c

9、ell dependent immunity Nonimmunogenic serogroup B polysaccharide remains a problem Proteins are vaccine candidates. 11Neisseria Gonorrhoeae Bacteriology Chocolate agar and CO2 are required Fresh isolates have pili LPS, LOS, and OMPs are in outer membraneOpa proteins are adherence OMPs 12Virulence fa

10、ctorsReceptors for human transferrinCapsule Pili (fimbriae)Cell membrane proteinsLipooligosaccharide(LOS)Immunoglobulin A protease :cleaves IgA on mucosal surfaces13Antigenic heterogeneity of N.gonorrhoeaAntigen Number of types Pili hundreds Por protein PorA 18 subtypesporB 28 subtypesOpa (protein I

11、I)Many (perhaps hundreds)Rmp (protein III)1 Lipoligosaccharide Eight or more Fbp (iron-binding protein)1Lip (H8)1IgA1 protease 214Antigenic variation Pili, OMPs, and LOS undergo antigenic variation Genes for pilin subunits may be expressed or silentRecombination between multiple genes Outercome may

12、be nonfunctional or antigenically altered pili Multiple Opa genes may be on or off Translational frame shift controls the switch 15Gonococcal antigenic variation 16Gonorrhea Epidemiology Rates among adolescents are high and increasing Inability to detect asymptomatic cases hampers control Risk of se

13、xual contact is up to 50%Asymptomatic cases are highest in women Nonsexual transmission is rare 17Gonorrhea in men and women18Acute urethritisCervicitis UrethritisLocal complications Pathogenesis Attachement and invasion 1 Pili and Opa proteins mediate attachment 2 Gonococci induce their own phagocy

14、tosis 3 Bacteria quickly pass to submucosa Survival in the submucosa 1 recepotrs scavenge iron 2 sialated LOS acts like a capsule 3 phagocytosed gonococci resist killing 19Pathogenesis Spread and dissemination Local spread :to epididymis and fallopian tubes LPS/LOS and peptidoglycan shedding cause l

15、ocal injury Reflux during menses may facilitate spread.Genetic regulation of virulence Regulation, recombination, and translational changes deploy virulence factors20Immunity Antibody response is weakGonococcus varies multiple structures to avoid immune surveillance 21Gonorrhea: clinical aspects Man

16、ifestations Genital Gonorrhea Other local infections Pelvic inflammatory disease (PID) Disseminated gonococcal infection (DGI) Purulent conjunctivitis : birth 22Pelvic inflammatory disease (PID):23Diagnosis Gram smear Direct smear is useful in men Interfering flora complicates interpretation in wome

17、n Culture Urethra and cervix are preferred culture sitesTransport media required unless plating is immediate Selective medium inhibits competing floraIsolates are identified by fermentation or immunoassay. Direct detection DNA amplification methods are combined with Chlamydia detection Serology No s

18、erologic test. 24Treatment Compliance dictates treatment on first encounter PBP alterations cause incremental resistance -Lactamase-producing strains are highly resistant Ceftriaxone, quinolones, and azithromycin are recommended therapy Quinolone and azithromycin resistance is still uncommon 25Prevention Condoms block transmission Vaccine strategies await better understanding of immunitySerologic test for screening?26Review questions Which of the following cell components