Who nose why skin's the way it is

Today I read about an interaction between two occupants of the human microbiome. The authors really do their findings a disservice by repeatedly referring to them in the context of the "nostril microbiome". What they really discuss is Staphylococcus aureus and various species of Propionibacterium. Both can be found in a variety of skin locations and especially on the face. Propionibacterium - and especially P. acne - is famous for causing the inflammation associated with all manner of nasty skin conditions. S. aureus is famous for causing many similar but often more medically worrisome infections. This paper shows how they might work together.*

Long story short: it's coproporphyrin III. Propionibacterium produces it and S. aureus uses it as a sign to start making biofilms.  A biofilm phenotype can improve survival in the face of the immune system, antibiotics, or even just physical stress.

Citation:
Wollenberg, M. S., Claesen, J., Escapa, I. F., Aldridge, K. L., Fischbach, M. A., and Lemon, K. P. (2014). Propionibacterium-Produced Coproporphyrin III Induces Staphylococcus aureus Aggregation and Biofilm Formation. mBio 5, e01286-14-.

*Anthropomorphism is to be avoided when discussing microbes. The English language, unfortunately, offers many opportunities for anthropomorphism-based rhetoric. In this case, "work together" is a bit misleading as this may not be a coordinated biological phenomenon. It may simply result from one species releasing a molecule and another species noticing it.

Today, I learned that the anaerobic gut microbiome occupant Bifidobacterium longum has been explored as a potential vector for treating cancer with gene therapy. B. longum is generally considered non-pathogenic and beneficial: it helps to balance pH in the gut, in part through production of lactic acid. A gut with the wrong pH can become susceptible to infection by bacterial pathogens. B. longum is added to some foods and supplements as a probiotic for this reason.

So what's going on with that gene therapy? A paper in 2000 by Yazawa et al. used a mouse model for an initial feasibility study. Though it doesn't appear that they actually used the method for tumor reduction, they did show that B. longum into mice with lung tumors could only be found in tumor tissue after 168 hours. That's presumably because the bacteria require an anaerobic (or, at least a hypoxic) environment to survice. Ideally, this means that B. longum bearing some kind of anti-tumor factor could be injected into or near a tumor with no pathogenic effect on any other tissues. B. longum can be killed off using common antibiotics; Yazawa et al. used ampicillin, though they only tried it in vitro. I'd be worried about long-term use with immunocompromised patients, though the exact anti-tumor material in play may be another critical factor.

The same research group was apparently still working on the idea as of 2010, when they published this review. A 2013 study by a different group looks like it had some success in using Bifidobacterium longum subsp. infantis as part of a method for treating bladder cancer in a mouse model.* This 2014 study just coated their Bifidobacterium in selenium, an elemental micronutrient which may have anti-tumor properties.


*I don't have access to the article so I'm not sure how well the method worked. The authors claim their treatment "exhibited the highest level of apoptosis" compared to controls so that could just mean they had a statistically-significant but limited effect on tumors. Cancer therapy isn't really my field so I'll give them the benefit of the doubt.

I read a review article about phage therapy today (citation below*) with the following opening sentence:

The human gut contains approximately 10¹⁵ bacteriophages (the ‘phageome’), probably the richest concentration of biological entities on earth.

Is that claim actually true? They cite this Lepage et al. Gut paper; those folks estimate that 10¹⁴ microorganisms (that is, distinct cells) live in any single human gut. We usually guess that an environment contains at least 10 times as many individual bacteriophage as potential host cells, so 10¹⁵ bacteriophages doesn't seem like a bad estimate. That being said, could there be a more densely-populated reservoir out there? I've seen population counts for chickens as high as 19 billion but I wasn't able to find any estimates of their gut microbiome diversity. We know they're a potential reservoir of pathogens and their population exceeds that of humanity.

Update: I've been thinking about this and realized that the phrase "richest concentration of biological entities" likely refers to a single human gut rather than the sum of all human gut microbiomes and viriomes. I like to think about ecological niches on a grand scale; the total number of different variations in phage genomes is higher when we include every similar environment in the total rather than the contents of just one human gut. My qualms about the superlative remain. I'd suspect that some sewer systems may contain richer, more diverse arrays of phages, and that's without employing much creativity. Could other species on this planet maintain more diverse microbiomes and/or viriomes?



*Dalmasso M, Hill C, Ross RP (2014) Exploiting gut bacteriophages for human health. Trends in microbiology 22: 399–405.

Power couples

I read about mutualism today. There has been - and continues to be - a long-running debate regarding the evolution of mutualism. The problem has often come down to a lack of evidence: we can be fairly confident that symbiotic mutualism is a real phenomenon but it's not always easy to demonstrate. We also know that many of the best examples of mutualism, such as chloroplasts, are the result of extensive evolution. Can mutualism emerge mutation, given the right circumstances for symbiotic partnerships to emerge?

A recent paper by Horn and Murray and accompanying summary article in Science show how it can happen. It's a neat, simple demonstration which would make a great elementary science class project.

Citation:
Horn EFY, Murray AW (2014) Niche engineering demonstrates a latent capacity for fungal-algal mutualism. Science 345: 94–98.

Unlabeled, but not forgotten.

Today I learned about Positive-Unlabeled learning, a type of semisupervised machine learning approach. This is the general problem: if you want a machine learning method to do binary classification, you need to start with examples of items which fit into one classification or the other. This is much easier and more efficient when you can safely say that everything in Column A is not in Column B and vice-versa. That isn't the case with some data. Rather, it's either labeled (Column A) or unlabeled (maybe Column B, or maybe Column A but just unlabeled).

PU learning can be used to define negative examples for protein function prediction.  Citation below:
Youngs N, Penfold-Brown D, Bonneau R, Shasha D (2014) Negative Example Selection for Protein Function Prediction: The NoGO Database. PLoS Comput Biol 10(6): e1003644. doi:10.1371/journal.pcbi.1003644.