Undiagnosed cases of fatal Clostridium-associated toxic shock in Californian women of childbearing age

Ho, Christine; Bhatnagar, Julu; Cohen, Adam L.; Hacker, Jill K.; Zane, Suzanne; Reagan, Sarah; Fischer, Marc; Shieh, Wun‐Ju; Guarner, Jeannette; Ahmad, Shabbir; Zaki, Sherif R.; McDonald, L. Clifford

doi:10.1016/j.ajog.2009.05.023

Cited by 39 publications

(30 citation statements)

References 24 publications

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“…Whereas the problem of clostridial infections is growing, there has been little research into the mechanisms detailing how the innate immune system recognizes and attempts to eliminate these potential pathogens. The increase in published reports of highly lethal C. sordellii gynecological infections in women of childbearing age (1,3,6) prompted further study of the pathogenesis of C. sordellii infections. To our knowledge, these studies show for the first time the receptors through which human macrophages internalize these toxigenic bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…The high mortality of C. sordellii infections is associated with a stereotypical toxic shock syndrome (2). A recent study estimated that nearly 1 in 200 deaths in women of reproductive age was associated with clostridial toxic shock, due to C. sordellii and/or the related Clostridium perfringens (3). An increased number of severe C. sordellii infections has been reported over the past decade, following childbirth and abortion (4)(5)(6).…”

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confidence: 99%

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The Class A Scavenger Receptor, Macrophage Receptor with Collagenous Structure, Is the Major Phagocytic Receptor for Clostridium sordellii Expressed by Human Decidual Macrophages

Thelen

Hao

Medeiros

et al. 2010

The Journal of Immunology

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Clostridium sordellii is an emerging pathogen associated with highly lethal female reproductive tract infections following childbirth, abortion, or cervical instrumentation. Gaps in our understanding of the pathogenesis of C. sordellii infections present major challenges to the development of better preventive and therapeutic strategies against this problem. We sought to determine the mechanisms whereby uterine decidual macrophages phagocytose this bacterium and tested the hypothesis that human decidual macrophages use class A scavenger receptors to internalize unopsonized C. sordellii. In vitro phagocytosis assays with human decidual macrophages incubated with pharmacological inhibitors of class A scavenger receptors (fucoidan, polyinosinic acid, and dextran sulfate) revealed a role for these receptors in C. sordellii phagocytosis. Soluble macrophage receptor with collagenous structure (MARCO) receptor prevented C. sordellii internalization, suggesting that MARCO is an important class A scavenger receptor in decidual macrophage phagocytosis of this microbe. Peritoneal macrophages from MARCO-deficient mice, but not wild-type or scavenger receptor AI/II–deficient mice, showed impaired C. sordellii phagocytosis. MARCO-null mice were more susceptible to death from C. sordellii uterine infection than wild-type mice and exhibited impaired clearance of this bacterium from the infected uterus. Thus, MARCO is an important phagocytic receptor used by human and mouse macrophages to clear C. sordellii from the infected uterus.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Class A Scavenger Receptor, Macrophage Receptor with Collagenous Structure, Is the Major Phagocytic Receptor for Clostridium sordellii Expressed by Human Decidual Macrophages

Thelen

Hao

Medeiros

et al. 2010

The Journal of Immunology

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“…Therefore, the number of known C. sordellii-associated infections, although low, may be underreported (19,29). Furthermore, unsafe abortion practices in developing countries cause large mortality rates due to complicating infections (24,34).…”

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confidence: 99%

Requirements for Germination ofClostridium sordelliiSporesIn Vitro

Ramírez

Abel-Santos

2010

J Bacteriol

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Clostridium sordellii is a spore-forming, obligately anaerobic, Gram-positive bacterium that can cause toxic shock syndrome after gynecological procedures. Although the incidence of C. sordellii infection is low, it is fatal in most cases. Since spore germination is believed to be the first step in the establishment of Bacilli and Clostridia infections, we analyzed the requirements for C. sordellii spore germination in vitro. Our data showed that C. sordellii spores require three structurally different amino acids and bicarbonate for maximum germination. Unlike the case for Bacilli species, D-alanine had no effect on C. sordellii spore germination. C. sordellii spores germinated only in a narrow pH range between 5.7 and 6.5. In contrast, C. sordellii spore germination was significantly less sensitive to temperature changes than that of the Bacilli. The analysis of the kinetics of C. sordellii spore germination showed strong allosteric behavior in the binding of L-phenylalanine and L-alanine but not in that of bicarbonate or L-arginine. By comparing germinant apparent binding affinities to their known in vivo concentrations, we postulated a mechanism for differential C. sordellii spore activation in the female reproductive tract.

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“…To better address this issue, we utilized an established mouse model of intrauterine (i.u.) infection with C. sordellii (24), since this pathogen is an emerging cause of life-threatening reproductive tract infections in young women (26). Mice (n ϭ 3 per group) were inoculated i.u.…”

Section: Figmentioning

confidence: 99%

TcsL Is an Essential Virulence Factor inClostridium sordelliiATCC 9714

et al. 2011

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Clostridium sordellii is an important pathogen of humans and animals, causing a range of diseases, including myonecrosis, sepsis, and shock. Although relatively rare in humans, the incidence of disease is increasing, and it is associated with high mortality rates, approaching 70%. Currently, very little is known about the pathogenesis of C. sordellii infections or disease. Previous work suggested that the lethal large clostridial glucosylating toxin TcsL is the major virulence factor, but a lack of genetic tools has hindered our ability to conclusively assign a role for TcsL or, indeed, any of the other putative virulence factors produced by this organism. In this study, we have developed methods for the introduction of plasmids into C. sordellii using RP4-mediated conjugation from Escherichia coli and have successfully used these techniques to insertionally inactivate the tcsL gene in the reference strain ATCC 9714, using targetron technology. Virulence testing revealed that the production of TcsL is essential for the development of lethal infections by C. sordellii ATCC 9714 and also contributes significantly to edema seen during uterine infection. This study represents the first definitive identification of a virulence factor in C. sordellii and opens the way for in-depth studies of this important human pathogen at the molecular level.

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Undiagnosed cases of fatal Clostridium-associated toxic shock in Californian women of childbearing age

Cited by 39 publications

References 24 publications

The Class A Scavenger Receptor, Macrophage Receptor with Collagenous Structure, Is the Major Phagocytic Receptor for Clostridium sordellii Expressed by Human Decidual Macrophages

The Class A Scavenger Receptor, Macrophage Receptor with Collagenous Structure, Is the Major Phagocytic Receptor for Clostridium sordellii Expressed by Human Decidual Macrophages

Requirements for Germination ofClostridium sordelliiSporesIn Vitro

TcsL Is an Essential Virulence Factor inClostridium sordelliiATCC 9714

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