Friday, March 28, 2014

Pichia vs Candida


       Time and again, in this blog, I have written about the effects of microbiome. One of the earliest concepts in field of microbiome, by competing with other pathogenic organisms they provide the earliest level of defence. That is one of the reason why our immune system is tolerant to them. When I say "Microbiome", most of the papers to date published, reflects the bacterial population. There are relatively literature on fungal microbiome.

Photo 1: Oral candidiasis.
     HIV doesn't need any introduction in this webpage. In clinical context, HIV is usually suspected when they make an appearance with infections of low pathogenic organism. In other words, features suggestive of immuno-compromised state. There is a whole range of list, of what the organism can be. But, there are a couple of signature organisms- Oral thrush by Candida species, Cryptococcal meningitis, Respiratory infection by pneumocystis jiroveci. In this blogpost, we will consider Candida infection.

      Just have a look at Photo 1. The photo depicts how bad a oral candidiasis can be. There is very sparse literature, on distribution of Candida species in healthy population. There is probably a huge variation. C albicans, is seen in a good number of healthy individuals. So why does candida become a problem in HIV infected patients. The most obvious explanation is that the HIV reduces immune barrier and so candida doesn't have to fight it out. Exactly how does a candida decide that its time to attack, is not known. There has been a lot of speculation in this field. Eh, possibly. But there seems to be a better explanation.

     There has been some earlier hints that perhaps there is a role of microbiome. A new study published in PLOS, looked at the changes in fungal and bacterial microbiome, using the metagenomic approach. By studying salivary samples from 12 HIV infected patients and 12 controls, they characterised the most common population and labelled them as COM (Core oral Mycobiome) and COB (Core oral bacteriome). The COB and COM, defines what is seen more commonly, thus excluding the variation. In the COB group 14 species where found, 13 was found common between HIV and control group. In COM, C albicans was seen in both groups. What was striking is that another member of flora, pichia was seen to negatively correlate in numbers.

    On further investigation, the data unfolds that Pichia sp actively inhibits Candida, Aspergillus and Fusarium. Pichia was able to compete with candida for nutrition, inhibited virulence factors and biofilm formation. The effects was seen due to an uncharacterised molecule present in the culture supernatant medium, tentatively named as PSM (Pichia spent medium)

     This is a first study of its kind. As the author suggests, there is a lot of potential in identifying the molecule so as to treat patients suffering from oral candidiasis. But, I speculate that Pichia can be a good candidate in investigating its use a probiotic. Or maybe saliva transplant is the future (Just as stool transplant is now making headlines).
Xu J, & Mitchell TG (2003). Geographical differences in human oral yeast flora. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 36 (2), 221-4 PMID: 12522756

de Repentigny L, Lewandowski D, Aumont F, Hanna Z, & Jolicoeur P (2009). Oral mucosal cell response to Candida albicans in transgenic mice expressing HIV-1. Methods in molecular biology (Clifton, N.J.), 470, 359-68 PMID: 19089395

Mukherjee PK, Chandra J, Retuerto M, Sikaroodi M, Brown RE, Jurevic R, Salata RA, Lederman MM, Gillevet PM, & Ghannoum MA (2014). Oral Mycobiome Analysis of HIV-Infected Patients: Identification of Pichia as an Antagonist of Opportunistic Fungi. PLoS pathogens, 10 (3) PMID: 24626467

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