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Thinking about the vagina

I spent the better part of several days last week discussing a fungus that lives in the vagina. I invited a seminar speaker, who studies Candida albicans colonization of mucosal surfaces, which includes the mouth, intestine, and vagina, among other sites. C. albicans is a normal part of the human flora that does not appear to be detrimental or beneficial (a commensal).  During our discussions, which usually took place a local watering holes, it became clear to me that different mammalian species can vary markedly when it comes to the indigenous flora and ultimately the physiology of the vaginal tract.

In women, the vagina is a fairly acidic environment. This is due to the action of Lactobacillus, a bacterium that grows well in the vaginal tract. Lactobacilli generates copious amounts of lactic acid from the metabolism of complex sugars. Lactic acid, as the name suggests, is acidic. The acidic pH in the vagina, due to lactic acid accumulation, inhibits the growth of most other microbes with the notable exception of C. albicans, a fungus. Fungi are extremely tolerant of acidic environments, at least in comparison to many bacteria.

Although C. albicans can grow reasonable well at the pH found in the vagina, it’s growth is limited by the vast abundance of Lactobacilli. Nutrients are not unlimited, so the faster growing Lactobacilli outcompete the slower growing C. albicans. Not surprisingly, if the Lactobacillus population is reduced, for example by broad spectrum antibiotic use or douching, then C. albicans can flourish, which can result in a yeast infection. (It can also lead to bacterial vaginosis, but this is less common.)

What is interesting, at least to me, is that vaginal pH of a female mouse is neutral. Based on this bit of information, you may not be surprised to learn that the murine vaginal tract is not colonized by Lactobacillus (therefore no lactic acid made and no vaginal acidic pH). Since the murine vaginal pH is not as acidic as a woman’s, you might expect C. albicans to do well there (as observed in women with a less acidic vaginal pH). However, C. albicans is not a normal colonizer of the mouse vagina. That being said, we can infect the murine vaginal tract in the lab with C. albicans. Indeed, when we do this, it appears that mice respond similarly to C. albicans as women with a yeast infection. What this tells us is that in the vaginal trac, C. albicans does not appear to be concerned with the environmental pH in regards to disease symptoms. This actually makes sense as recent studies have shown that women who have recurrent vaginal yeast infections (3 or more incidents a year during their child bearing years (yes hormones play a big role here)), the problem is how their bodies respond to C. albicans not due to anything specifically the fungus is doing.

To someone who works on how C. albicans responds to environmental pH, these results may seem disappointing. However, I for one find them intriguing. One primary reason we study the C. albicans response to environmental pH is that environmental pH has a dramatic effect on how this fungus grows. In acidic environments, C. albicans grows as a yeast indistinguishable from the Bakers yeast (Saccharomyces cerevisiae) you can buy in the grocery store. In neutral or alkaline environments, C. albicans grows in the hyphal form (analogous to the hairy mold growing on the bread you baked but left sitting around too long). Besides being a striking phenotype, the transition between the yeast and hyphal growth forms is critical for disease and presumably for colonization as a commensal.

In summary, the ability to switch between the yeast and hyphal growth forms is critical for disease and environmental pH directly controls morphology. The problem or point of interest is that the environmental pH in the vagina of two distinct mammals varies markedly yet disease appears similar. This suggests that other environmental factors contribute to morphogenesis (true) and/or that within the vaginal tract C. albicans morphology is not important (potentially true). Support for this latter idea comes from Candida glabrata, a yeast that commonly colonizes the vaginal tract that is closely related to S. cerevisiae (the one you can buy in the supermarket). The key here is that C. glabrata only grows in the yeast form and is readily able to cause yeast infections.

A couple of accessory points. 1, A picture may be worth a thousand words, but some posts are not amenable to google searches; 2, You can get some interesting looks from patrons of the local watering hole discussing the microbial contingent of the vagina.

2 comments:

rachelnygaard said...

What type (hyphal or yeast) actually grows in the vaginal tract of either species?
Doesn't the pH change over the course of the menstral cycle? Has anyone looked to see if the pH changes during the course of the disease?

The Lorax said...

In the case of C. albicans, both yeast and hyphal forms are found in the vaginal tract (and presumably everywhere C. albicans is found). For example, here's a recent study using vaginal epithelia.

Yes the pH changes over the menstral cycle, as menstral blood flow from the uterus raises the pH.

Regarding disease, vaginal candidiasis has been n issue for women presumably as long as there has been women. Before topical treatments, menstruation was something to look forward to in women suffering from a candidiasis episode. The normal flora was often restored to 'normal'. Whether this was due to Candida being flushed out, physiological changes within the vagina that inhibited Candida growth, or a little bit of both is something I do not know though.