Does the Cervicovaginal Microbiome Facilitate Transmission of Neisseria gonorrhoeae From Women to Men? Implications for Understanding Transmission of Gonorrhea and Advancing Vaccine Development.
Does the Cervicovaginal Microbiome Facilitate Transmission of Neisseria gonorrhoeae From Women to Men? Implications for Understanding Transmission of Gonorrhea and Advancing Vaccine Development.
复制标题
宫颈阴道微生物组是否促进淋病奈瑟菌从女性传播到男性？
DOI：
10.1093/infdis/jiw331
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Shafer,WilliamM
中科院分区：
文献类型：
--
作者：
Shafer,WilliamM
Gonorrhea, with an estimated 78 million cases in 2012 [1], continues to be a worldwide public health problem. With the emergence of strains resistant to frontline antibiotics, including the current dual therapy of azithromycin and ceftriaxone [2], this global crisis will only worsen in the absence of new antimicrobials entering clinical practice. The late John Tapsall characterized the etiologic agent of this sexually transmitted infection, Neisseria gonorrhoeae, as chameleon-like [3] because of its remarkable ability to change its surface structure, owing to phase and antigenic variation of surface proteins and lipooligosaccharide (LOS), as well as to presenting structures resembling host antigens (molecular mimicry). Furthermore, N. gonorrhoeae has the remarkable ability to resist numerous mediators of innate host defense [4], in addition to dampening humoral responses [5], resulting in nonprotective infection. While infection in men is frequently symptomatic because of a robust proinflammatory response, infection in females is often asymptomatic. This difference is likely multifactorial, but past studies have suggested that N. gonorrhoeae enters male and female epithelial cells at the urogenital mucosal layer through different receptors (Figure 1)[6] and that such receptor-specific invasion may influence signaling events that affect the extent of the proinflammatory response. A long-standing interest has been how N. gonorrhoeae changes its surface structure to facilitate receptorspecific epithelial cell invasion during transmission between the sexes. We now have a possible scenario that answers this question, with the studies by Ketterer et al [7] reported in this issue of The Journal of Infectious Diseases. As described below, their findings are exciting in that they implicate sialidases provided by the cervicovaginal microbiome as facilitators of rendering N. gonorrhoeae more amenable to infection of the male urethra. As background, a key modification of the N. gonorrhoeae cell surface that affects bacterial invasion of host cells involves the transfer of sialic acid to the terminal galactose of the α-chain of LOS (the N-acetyllactosamine region); this LOS modification also provides N. gonorrhoeae with the ability to resist complement-dependent killing by normal human serum. Relevant to host cell invasion, sialylation of N. gonorrhoeae LOS influences sex-specific host epithelial cell invasion. Sialylation of LOS, first described by the late Sir Harry Smith and colleagues [8], occurs within both male and female epithelial cells (Figure 1). Transfer of sialic acid from cytidinemonophosphate-N-acetylneuraminic acid (hereafter,“sialic acid”) to the terminal galactose occurs through the action of the N. gonorrhoeae–encoded α2, 3-sialyltransferase; N. gonorrhoeae does not have the capacity to synthesize sialic acid and relies on intracellular stores for this modification of the LOS. While a number of past studies have concentrated on the enzymatic properties of this reaction and the biologic consequences of sialylation of LOS, little is known about the importance of this modification during transmission of N. gonorrhoeae between the sexes. The work of Ketterer et al presented herein strongly suggests that, during cevicovaginal infection, bacteria in the female microbiome provide sialidases that remove sialic acid from the terminal galactose of the N. gonorrhoeae LOS N-acetyllactosamine region prior to transmission of the bacteria to a male partner. This action would render N. gonorrhoeae ready to engage urethral epithelial cells via the asialoglycoprotein receptor (Figure 1); this receptor only binds N. gonorrhoeae lacking sialic acid attached to the N-acetyllactosamine–bearing LOS. Briefly …
