Characteristics of murine model of genital infection with Chlamydia trachomatis and effects of therapy with tetracyclines, amoxicillin-clavulanic acid, or azithromycin

Beale, A S; Upshon, P. A.

doi:10.1128/aac.38.9.1937

Cited by 18 publications

(16 citation statements)

References 31 publications

(25 reference statements)

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“…It remains unclear, however, why some species (such as M. pneumoniae and M. pulmonis) require progesterone treatment for infection whereas others (such as M. fermentans) colonize the genital tract only after estrogen treatment (10). Estradiol treatment increases the susceptibility of BALB/c mice to Neisseria gonorrhoeae infection (21), whereas progesterone enhances murine susceptibility to C. trachomatis (46) and C. muridarum (1). Despite the similar cell-associated phenotypes of these bacterial species, it is evident that systemic manipulation of sex hormones dramatically affects susceptibility, duration of infection, and pathological outcomes in murine STI models.…”

Section: Discussionmentioning

confidence: 99%

Mycoplasma genitalium Rapidly Disseminates to the Upper Reproductive Tracts and Knees of Female Mice following Vaginal Inoculation

2010

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Mycoplasma genitalium is an emerging sexually transmitted infection and in women isMycoplasma genitalium is an emerging sexually transmitted pathogen that was first identified as a cause of inflammatory urogenital disease in men (reviewed in references 15 and 18). Importantly, M. genitalium infections in women have also been associated with inflammatory syndromes, including cervicitis (8,24,27,32,50) and pelvic inflammatory disease (12), and (serologically) with impaired fertility (4, 37). Mechanistically, M. genitalium has previously been shown to activate highly expressed Toll-like receptors in reproductive tract epithelia, leading to inflammation (28,29). Collectively, these associations have led to an increased awareness of M. genitalium as a pathogen that could adversely affect reproductive health. It may also be of considerable importance that M. genitalium is strongly associated with HIV infections in men and women (reviewed in reference 31), suggesting that reproductive tract infections by M. genitalium may increase the likelihood of acquiring or transmitting other genital pathogens.Although the genital tract seems to be a preferred site of colonization, M. genitalium also has been a suspected cause of reactive arthritis, since DNA was previously detected in the knee joints of arthritic patients (45, 47) and in synovial fluid from temporomandibular joints (23). It is possible that M. genitalium may be a cause of sexually acquired reactive arthritis, but to date, no direct evidence exists for an association with an arthritic condition. Furthermore, no published reports have addressed the ability of M. genitalium to disseminate from the vagina to colonize the joint tissues or upper genital tract tissues. Similarly, there is a lack of experimental evidence for the causal associations of M. genitalium infection with inflammatory disease syndromes in women.As epidemiological data continue to implicate M. genitalium as a cause of reproductive tract disease, relevant animal models to investigate pathogenesis and evaluate therapeutic interventions are of utmost importance. Five years after the initial isolation of M. genitalium from men with urethritis (48), several large-animal species, including male cynomolgus monkeys (Macaca fascicularis), male chimpanzees (Pan troglodytes), female squirrel monkeys (Saimiri sciureus), female tamarins (Saguinus mystax), and female marmosets (Callithrix jacchus [44]), were found to be susceptible to experimental urogenital infection. These studies provided excellent preliminary evidence that M. genitalium could establish infection of female reproductive tract tissues. However, the cost of developing and maintaining primate and large-animal models prohibits experimentation employing larger-scale studies to address biological variability as part of an effective model of reproductive tract disease. In contrast, rodent models are cost-effective and afford the opportunity to investigate larger study populations of animals with specific genetic characteristics. Such models also allo...

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Section: Discussionmentioning

confidence: 99%

Mycoplasma genitalium Rapidly Disseminates to the Upper Reproductive Tracts and Knees of Female Mice following Vaginal Inoculation

2010

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“…C. trachomatis within the human population remains manageable [7,8], although the potential for resistant forms has been reported [13]. Conversely, C. suis , which primarily infects swine, has shown to resist clearance at a herd level with a diverse range of antibiotics [12], and is the first of the Chlamydiaceae to develop stable TET-resistant forms in vivo [30]. C. psittaci responds well to TET or MAC treatment in humans and birds at an individual level [9,31], however, no reliable treatment is known for infections in cattle [6,32].…”

Section: Overview Of Chlamydiaceaementioning

confidence: 99%

Natural Products for the Treatment of Chlamydiaceae Infections

et al. 2016

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Due to the global prevalence of Chlamydiae, exploring studies of diverse antichlamydial compounds is important in the development of effective treatment strategies and global infectious disease management. Chlamydiaceae is the most widely known bacterial family of the Chlamydiae order. Among the species in the family Chlamydiaceae, Chlamydia trachomatis and Chlamydia pneumoniae cause common human diseases, while Chlamydia abortus, Chlamydia psittaci, and Chlamydia suis represent zoonotic threats or are endemic in human food sources. Although chlamydial infections are currently manageable in human populations, chlamydial infections in livestock are endemic and there is significant difficulty achieving effective treatment. To combat the spread of Chlamydiaceae in humans and other hosts, improved methods for treatment and prevention of infection are needed. There exist various studies exploring the potential of natural products for developing new antichlamydial treatment modalities. Polyphenolic compounds can inhibit chlamydial growth by membrane disruption, reestablishment of host cell apoptosis, or improving host immune system detection. Fatty acids, monoglycerides, and lipids can disrupt the cell membranes of infective chlamydial elementary bodies (EBs). Peptides can disrupt the cell membranes of chlamydial EBs, and transferrins can inhibit chlamydial EBs from attachment to and permeation through the membranes of host cells. Cellular metabolites and probiotic bacteria can inhibit chlamydial infection by modulating host immune responses and directly inhibiting chlamydial growth. Finally, early stage clinical trials indicate that polyherbal formulations can be effective in treating chlamydial infections. Herein, we review an important body of literature in the field of antichlamydial research.

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“…Genital swabs were collected on days 3, 6, and 9 before antibiotic treatment and on days 4 and 7 after antibiotic treatment. Antibiotic treatments were based on regimens given clinically for chlamydial infection (12). Mice were euthanized after 11 days after initiation of antibiotic treatment, and cecal epithelial cells were collected for chlamydial isolation on a HeLa cell monolayer.…”

Section: Methodsmentioning

confidence: 99%

Differential Susceptibilities to Azithromycin Treatment of Chlamydial Infection in the Gastrointestinal Tract and Cervix

Yeruva

Melnyk

Spencer

et al. 2013

Antimicrob Agents Chemother

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Evidence from animal studies suggests that chlamydiae may persist in the gastrointestinal tract (GI) and be a reservoir for reinfection of the genital tract. We hypothesize that there may be a differential susceptibility of organisms in the GI and genital tracts. To determine the effect of azithromycin on persistent chlamydial gut infection, C57BL/6 and BALB/c mice were infected orally and genitally and treated with azithromycin (Az) orally (20, 40, or 80 mg/kg of body weight), and the numbers of chlamydiae were determined from cervix and cecal tissues. The Az concentration in the cecum and cervix was measured by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). Az treatment cleared genital infection in both C57BL/6 and BALB/c mice; however, GI infection was not cleared with the same doses. HPLC data showed the presence of Az at both sites of infection, and significant amounts of Az were measured in treatment groups. However, no significant difference in Az levels between the cecum and the cervix was observed, indicating similar levels of Az reaching both sites of infection. These data indicate that antibiotic levels that are sufficient to cure genital infection are ineffectual against GI infection. The results suggest a reevaluation of antibiotic therapy for chlamydial infection. Chlamydia trachomatis remains the most commonly reported infectious disease in the United States. More than 1.4 million cases of chlamydial infection were reported to the CDC in 2011, the largest number of cases ever reported to the CDC for any infection. The reported numbers of cases are highest for adolescent girls (15 to 19 years of age) and young women (20 to 24 years of age). A major problem with chlamydial infections is that in the majority of cases, the infections remain subclinical and "persist" for long periods of time if not treated. Of course, it is difficult to determine if the "persistent" infections are the original infection or the result of treatment failure or the individual has become reinfected from a partner.Alternatively, it is possible that women become autoinfected from the gastrointestinal (GI) tract. It should be noted that in most animals, including birds, sheep, cattle, pigs, mice, and guinea pigs, the natural site of chlamydial infection is the GI tract, and the organisms are transmitted by the fecal-oral route. We and others have reported that mice remain infected in the GI tract with Chlamydia muridarum indefinitely in the absence of pathology (1-3) even though genital infections resolve within 3 to 4 weeks with an intense inflammatory response. Because chlamydiae persist in the GI tract of other mammalian and avian species, it is plausible that chlamydiae may also establish long-term colonization of the human GI tract. In fact, there is ample evidence that women become infected orally and that chlamydiae can be isolated from rectal swabs in the absence of anal intercourse (4). Jones and colleagues showed that women may be positive in the rectum but negative in the cervix (4...

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Characteristics of murine model of genital infection with Chlamydia trachomatis and effects of therapy with tetracyclines, amoxicillin-clavulanic acid, or azithromycin

Cited by 18 publications

References 31 publications

Mycoplasma genitalium Rapidly Disseminates to the Upper Reproductive Tracts and Knees of Female Mice following Vaginal Inoculation

Mycoplasma genitalium Rapidly Disseminates to the Upper Reproductive Tracts and Knees of Female Mice following Vaginal Inoculation

Natural Products for the Treatment of Chlamydiaceae Infections

Differential Susceptibilities to Azithromycin Treatment of Chlamydial Infection in the Gastrointestinal Tract and Cervix

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