To the Editor:
Ethical restrictions prohibiting experimental infection of women with Neisseria gonorrhoeae have limited studies of the natural history of gonococcal infection in women. We congratulate Stupiansky and colleagues on publication of their article entitled “The Natural History of Incident Gonococcal Infection in Adolescent Women” in the August 2011 issue of Sexually Transmitted Diseases.1 The findings presented make a significant contribution to our knowledge of gonococcal infection in women, especially about colonization load, symptomology, and coinfection with Chlamydia trachomatis. We are particularly excited by the observation that gonococcal shedding was higher in women with concurrent chlamydial infection than in those infected with N. gonorrhoeae alone.1 This finding is consistent with our recent report that gonococcal colonization was significantly higher in experimentally infected female mice that have a preexisting infection with Chlamydia muridarum, the mouse strain of chlamydia.2
The mouse coinfection model used in our study was adapted from a well-characterized mouse model of gonococcal genital tract infection,3 and while near simultaneous publication of the reports by Stupiansky et al1 and Vonck et al2 prevented citation of the other group's findings, we were surprised by the authors' comment that “no animal model has been established (for N. gonorrhoeae) that adequately replicates human infection.”1 The literature cited in support of this comment is outdated, reflecting the status of animal modeling before 1989.1 Since publication of the estradiol-treated mouse model of gonococcal genital tract infection by our laboratory in 1999,3 at least 20 studies using this model have been published in peer-reviewed journals.4 Many aspects of gonococcal infection in women are reproduced by experimental infection of female mice, as recently reviewed by Jerse et al.4 As early as 1947, a hormonal influence on gonococcal colonization in women was described, which has since been demonstrated to occur during murine infection.5 Similarly, patterns of opacity protein selection in female mice are similar to those reported for human cervical isolates in the 1970s. In addition, several gonococcal genes hypothesized to play a role in pathogenesis in vitro confer the predicted phenotype during murine infection. The murine immune response to N. gonorrhoeae also has similarities with humans, including lack of a protective response and a role for IL-17. The mouse model is uniquely positioned for mechanistic studies of these and other findings through the use of genetically defined mouse strains. Also, while numerous host-restrictions limit the use of mice to fully mimic gonorrhea in humans, recent advances in transgenic mice may alleviate some of these concerns.4
The available mouse models of gonorrhea and gonorrhea chlamydia coinfection should facilitate investigation of the molecular basis of enhanced gonococcal infection observed in chlamydia-infected humans and mice. Important studies of natural gonococcal infection in women, such as that by Stupiansky et al,1 are complemented by mechanistic studies in animal models that together lead to a better understanding of gonorrhea in women.
Rachel Vonck Stankowski, PhD
Marshfield Clinic Research Foundation
Jessica G. Cole, PhD
Center for Drug Evaluation and Research
Food and Drug Administration
Silver Spring, MD
Ann E. Jerse, PhD
Department of Microbiology and Immunology
Uniformed Services University
1. Stupiansky NW, Van Der Pol B, Williams JA, et al.. The natural history of incident gonococcal infection in adolescent women. Sex Transm Dis 2011; 38: 750–754 .
2. Vonck RA, Darville T, O'Connell CM, et al.. Chlamydial infection increases gonococcal colonization in a novel murine coinfection model. Infect Immun 2011; 79: 1566–1577 .
3. Jerse AE. Experimental gonococcal genital tract infection and opacity protein expression in estradiol-treated mice. Infect Immun 1999; 67: 5699–5708 .
4. Jerse AE, Wu H, Packiam M, et al.. Estradiol-treated female mice as surrogate hosts for Neisseria gonorrhoeae
genital tract infections. Front Microbiol 2011; 2: 107 .
5. Cole JG, Fulcher NB, Jerse AE. Opacity proteins increase Neisseria gonorrhoeae
fitness in the female genital tract due to a factor under ovarian control. Infect Immun 2010; 78:1629–1641.