The Vaginal Microflora of Pig-Tailed Macaques and the Effects of Chlorhexidine and Benzalkonium on This Ecosystem

Patton, Dorothy L.; Sweeney, Yvonne Cosgrove; Rabe, Lorna K.; Hillier, Sharon L.

doi:10.1097/00007435-199611000-00009

Cited by 56 publications

(48 citation statements)

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“…We sought to develop an animal model of persistent infection to study gene variation in M. genitalium in the context of a normal immune response. Female pig-tailed macaques (M. nemestrina) were chosen for this purpose because of the similarities of their reproductive tract anatomy, menstrual cycle, and vaginal flora to those of humans (53)(54)(55) and the previous success using this species in models of genital tract infection with other human pathogens, including Chlamydia trachomatis (56)(57)(58)(59)(60)(61)(62)(63), Trichomonas vaginalis (64), and simian-human immunodeficiency virus (SHIV) coinfection with C. trachomatis and T. vaginalis (65). Prior to inoculation, the M. genitalium-negative status of a candidate primate was confirmed by culture and qPCR of preinoculation genital tract specimens (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Experiments with the female pig-tailed macaque, a species with the advantages of small size, a reproductive physiology similar to that of humans, and a greater availability for research purposes, will expand the findings of these animal models. Previous studies determined that the normal vaginal flora cultured from female macaques is similar to bacteria recovered from the human vagina (55). Comparison of the macaque and human microbiomes by molecular methods, which is under way (Dorothy L. Patton, personal communication), will ascertain whether those similarities extend to unculturable organisms.…”

Section: Discussionmentioning

confidence: 99%

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Persistence, Immune Response, and Antigenic Variation of Mycoplasma genitalium in an Experimentally Infected Pig-Tailed Macaque (Macaca nemestrina)

et al. 2013

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Mycoplasma genitalium is a sexually transmitted pathogen associated with several acute and chronic reproductive tract disease syndromes in men and women. To evaluate the suitability of a pig-tailed macaque model of M. genitalium infection, we inoculated a pilot animal with M. genitalium strain G37 in the uterine cervix and in salpingeal pockets generated by transplanting autologous Fallopian tube tissue subcutaneously. Viable organisms were recovered throughout the 8-week experiment in cervicovaginal specimens and up to 2 weeks postinfection in salpingeal pockets. Humoral and cervicovaginal antibodies reacting to MgpB were induced postinoculation and persisted throughout the infection. The immunodominance of the MgpB adhesin and the accumulation of mgpB sequence diversity previously observed in persistent human infections prompted us to evaluate sequence variation in this animal model. We found that after 8 weeks of infection, sequences within mgpB variable region B were replaced by novel sequences generated by reciprocal recombination with an archived variant sequence located elsewhere on the chromosome. In contrast, mgpB region B of the same inoculum propagated for 8 weeks in vitro remained unchanged. Notably, serum IgG reacted strongly with a recombinant protein spanning MgpB region B of the inoculum, while reactivity to a recombinant protein representing the week 8 variant was reduced, suggesting that antibodies were involved in the clearance of bacteria expressing the original infecting sequence. Together these results suggest that the pig-tailed macaque is a suitable model to study M. genitalium pathogenesis, antibody-mediated selection of antigenic variants in vivo, and immune escape. Mycoplasma genitalium is a recently recognized sexually transmitted pathogen associated with reproductive tract disease in men and women (reviewed in references 1 to 3). Infection with this organism has been associated with urethritis in men (4-6) and cervicitis (7-9), urethritis (10, 11), acute endometritis (12), chronic pelvic inflammatory disease (13), tubal factor infertility (14, 15), and preterm birth (16, 17) in women. When untreated or inappropriately treated, M. genitalium infection can persist for months to years (18-21), suggesting that this organism avoids elimination by the host immune response. Recent studies assessing M. genitalium treatment regimens have found that standard antibiotic therapy fails to cure a significant proportion of infections (reviewed in reference 1), highlighting the importance of a better understanding of M. genitalium pathogenesis so that effective treatment and prevention methods can be devised.The distinct flask-shaped morphology of M. genitalium cells can be attributed to its complex tip organelle involved in gliding motility (22-25) and adherence to host cells and inanimate surfaces (26-30). Included among the tip organelle-associated proteins are the major adhesin, MgpB (also known as MgPa or P140), and its accessory protein, MgpC (also known as P110), which is required for the sta...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Persistence, Immune Response, and Antigenic Variation of Mycoplasma genitalium in an Experimentally Infected Pig-Tailed Macaque (Macaca nemestrina)

et al. 2013

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“…First, the anatomy and physiology of the female reproductive tract are similar to those in humans. As in women, they have a 28-to 30-day menstrual cycle, and their vaginal microflora also closely resembles that of women (76,77). Second, pig-tailed macaques have a relatively quiet temperament and an ideal size, since they are large enough for most procedures but still manageable (77,78).…”

Section: Primate Models: Pig-tailed Macaquementioning

confidence: 99%

Animal Models for Studying Female Genital Tract Infection with Chlamydia trachomatis

2013

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Chlamydia trachomatis is a Gram-negative obligate intracellular bacterial pathogen. It is the leading cause of bacterial sexually transmitted disease in the world, with more than 100 million new cases of genital tract infections with C. trachomatis occurring each year. Animal models are indispensable for the study of C. trachomatis infections and the development and evaluation of candidate vaccines. In this paper, the most commonly used animal models to study female genital tract infections with C. trachomatis will be reviewed, namely, the mouse, guinea pig, and nonhuman primate models. Additionally, we will focus on the more recently developed pig model. Chlamydia trachomatis, a Gram-negative obligate intracellular bacterium, is the leading cause of bacterial sexually transmitted disease. World Health Organization values for 2008 estimated an annual increase of over 100 million genital tract infections with C. trachomatis worldwide (1). The incidence of cases is increasing in many countries (1, 2). Genital tract infections with C. trachomatis can cause cervicitis in women and urethritis in men. However, these infections remain largely subclinical in approximately 70% of women and 50% of men and consequently are often not detected (3). Untreated infections may lead to pelvic inflammatory disease, tubal scarring, ectopic pregnancy, infertility, and chronic pelvic pain in women, epididymitis in men, and infant pneumonia in children (4-7). Uncomplicated chlamydial infections can be treated easily with antibiotics, but once infection and pathology are established, treatment may be less effective. Asymptomatic individuals can be identified through screening programs, but this approach is likely to be too costly for developing countries. A vaccination program would be much cheaper and have a greater impact in controlling C. trachomatis infections worldwide. Computer modeling suggests that even a partially efficacious chlamydial vaccination program would rapidly reduce the prevalence of genital infection (8). Animal models are indispensable for the study of C. trachomatis infections and the development and evaluation of candidate vaccines. Various animal models have been developed, including mouse (9, 10), guinea pig (11, 12), nonhuman primate (13,14), pig (15), rat (16), and rabbit (17) models. Here, the most commonly used animal models to study female genital tract infections with C. trachomatis will be reviewed, namely, the mouse, guinea pig, and nonhuman primate models. Additionally, we will focus on the more recently developed pig model. MOUSE MODELSMice are the most commonly used animals to study genital chlamydial infections. The advantages of the mouse model are their small size, ease of handling, availability in sufficient amounts, and low cost. Moreover, there are many well-characterized inbred and knockout mouse strains available (18). The female mouse genital tract is susceptible to infection with both Chlamydia muridarum (9) and C. trachomatis (10), which has resulted in the establishment of two murine mod...

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“…[9][10][11] Cultivation biases are well known, 12 and recent studies that used molecular techniques to identify genital bacteria indicate that many of the bacteria that are present in the genital tract of women are not cultivable or are difficult to cultivate. 13,14 For example, bacteria from the genus Sneathia, in the phylum Fusobacteria, cannot be cultured using current methods, but make up a substantial proportion of the microbiota in some women with BV.…”

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confidence: 99%

Longitudinal Assessment of Pigtailed Macaque Lower Genital Tract Microbiota by Pyrosequencing Reveals Dissimilarity to the Genital Microbiota of Healthy Humans

Spear

Kersh

Guenthner

et al. 2012

AIDS Research and Human Retroviruses

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Vaginal bacterial communities play an important role in human health and have been shown to influence HIV infection. Pigtailed macaques (Macaca nemestrina) are used as an animal model of HIV vaginal infection of women. Since the bacterial microbiota could influence retrovirus infection of pigtailed macaques, the genital microbiota in 10 cycling macaques was determined by pyrosequencing. The microbiota of all macaques was polymicrobial with a median of 13 distinct genera. Strikingly, the genera Sneathia and Fusobacterium, both in the phylum Fusobacteria, accounted for 18.9% and 13.3% of sequences while the next most frequent were Prevotella (5.6%), Porphyromonas (4.1%), Atopobium (3.6%), and Parvimonas (2.6%). Sequences corresponding to Lactobacillus comprised only 2.2% of sequences on average and were essentially all L. amylovorus. Longitudinal sampling of the 10 macaques over an 8-week period, which spanned at least one full ovulatory cycle, showed a generally stable presence of the major types of bacteria with some exceptions. These studies show that the microbiota of the pigtailed macaques is substantially dissimilar to that found in most healthy humans, where the genital microbiota is usually dominated by Lactobacillus sp. The polymicrobial makeup of the macaque bacterial populations, the paucity of lactobacilli, and the specific types of bacteria present suggest that the pigtailed macaque microbiota could influence vaginal retrovirus infection.

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The Vaginal Microflora of Pig-Tailed Macaques and the Effects of Chlorhexidine and Benzalkonium on This Ecosystem

Abstract: These observations demonstrate that the vaginal microflora of the pig-tailed macaque is a useful model in which to further evaluate newly developed intravaginal contraceptives that may be microbicidal and/or virucidal before widespread intravaginal use in women.

Cited by 56 publications

References 6 publications

Persistence, Immune Response, and Antigenic Variation of Mycoplasma genitalium in an Experimentally Infected Pig-Tailed Macaque (Macaca nemestrina)

Persistence, Immune Response, and Antigenic Variation of Mycoplasma genitalium in an Experimentally Infected Pig-Tailed Macaque (Macaca nemestrina)

Animal Models for Studying Female Genital Tract Infection with Chlamydia trachomatis

Longitudinal Assessment of Pigtailed Macaque Lower Genital Tract Microbiota by Pyrosequencing Reveals Dissimilarity to the Genital Microbiota of Healthy Humans

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