Gonorrhoea Research Today is a free monthly online journal that collates and summarizes the latest research about Gonorrhoea, including details on symptoms, causes, stds, treatment, cures.
Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression.
Malott RJ, Keller BO, Gaudet RG, McCaw SE, Lai CC, Dobson-Belaire WN, Hobbs JL, St Michael F, Cox AD, Moraes TF, Gray-Owen SD
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada M5S 1A8.
Clinical and epidemiological synergy exists between the globally important sexually transmitted infections, gonorrhea and HIV. Neisseria gonorrhoeae, which causes gonorrhea, is particularly adept at driving HIV-1 expression, but the molecular determinants of this relationship remain undefined. N. gonorrhoeae liberates a soluble factor that potently induces expression from the HIV-1 LTR in coinfected cluster of differentiation 4-positive (CD4(+)) T lymphocytes, but this factor is not a previously described innate effector. A genome-wide mutagenesis approach was undertaken to reveal which component(s) of N. gonorrhoeae induce HIV-1 expression in CD4(+) T lymphocytes. A mutation in the ADP-heptose biosynthesis gene, hldA, rendered the bacteria unable to induce HIV-1 expression. The hldA mutant has a truncated lipooligosaccharide structure, contains lipid A in its outer membrane, and remains bioactive in a TLR4 reporter-based assay but did not induce HIV-1 expression. Mass spectrometry analysis of extensively fractionated N. gonorrhoeae-derived supernatants revealed that the LTR-inducing fraction contained a compound having a mass consistent with heptose-monophosphate (HMP). Heptose is a carbohydrate common in microbes but is absent from the mammalian glycome. Although ADP-heptose biosynthesis is common among Gram-negative bacteria, and heptose is a core component of most lipopolysaccharides, N. gonorrhoeae is peculiar in that it effectively liberates HMP during growth. This N. gonorrhoeae-derived HMP activates CD4(+) T cells to invoke an NF-κB-dependent transcriptional response that drives HIV-1 expression and viral production. Our study thereby shows that heptose is a microbial-specific product that is sensed as an innate immune agonist and unveils the molecular link between N. gonorrhoeae and HIV-1.
Published 19 June 2013 in Proc Natl Acad Sci U S A, 110(25): 10234-9.
Articles on Gonorrhoea published 22 April 2013:
Limits of the lab: diagnosing "latent gonorrhea," 1872-1910. Bull Hist Med, 87(1): 63-85.
One of the most heatedly contested disease entities in turn-of-the-century medicine was "latent gonorrhea," a condition first discussed in an 1872 paper published by the German-born gynecologist Emil Noeggerath. Although none of the bacteriological discoveries of the next few decades-including the isolation of the gonococcus in 1879-provided much evidence of its existence, by the 1890s most Western physicians and medical scientists had nonetheless come to believe that latent gonorrhea ... [Abstract] [Full-text]
Articles on Gonorrhoea published 15 April 2013:
Evolution of Neisseria gonorrhoeae is a continuing challenge for molecular detection of gonorrhoea: false negative gonococcal porA mutants are spreading internationally. Sex Transm Infect, 89(3): 197-201.
Molecular epidemiology of gonorrhoea in Wales (UK). Sex Transm Infect, 89(3): 267-72.
Articles on Gonorrhoea published 11 April 2013:
Decline in the prevalence of HIV and sexually transmitted infections among female sex workers in Benin over 15 years of targeted interventions. J Acquir Immune Defic Syndr, 63(1): 126-34.
Articles on Gonorrhoea published 25 March 2013:
Underrecognition of cervical Neisseria gonorrhoeae and Chlamydia trachomatis infections in pregnant patients in the ED. Am J Emerg Med, 31(4): 661-3.
Articles on Gonorrhoea published 5 March 2013:
Neisseria gonorrhoeae antimicrobial resistance among men who have sex with men and men who have sex exclusively with women: the Gonococcal Isolate Surveillance Project, 2005-2010. Ann Intern Med, 158(5): 321-8.
Articles on Gonorrhoea published 20 February 2013:
Articles on Gonorrhoea published 18 February 2013:
The prevalences of Neisseria gonorrhoeae and Chlamydia trachomatis infections among female sex workers in China. BMC Public Health, 13: 121.
© 2004-2013 Gonorrhoea Research Today. All Rights Reserved.