Are there bacteria in the brain?

BREAKING: I am posting this without much commentary because I have not had time yet to read the paper in full. A new report in PLOS ONE collates evidence that bacteria regularly inhabit the brain of immunocompromised brains. On the surface, the evidence seems pretty strong. mRNA detection and sequencing, in situ hybridizations, and brain tissue transplants from humans to mice....For those that would rather skip the science jargon, there is one press release from Boston.com. Is the brain microbiome a new frontier? As a related point, we published a paper in 2011 in Genetics on immunocompromised wasps that have remarkable bacterial infections in their brains (Figure 2D), resulting in altered mate preference behavior (Figure 8).

Citation: Branton WG, Ellestad KK, Maingat F, Wheatley BM, Rud E, et al. (2013) Brain Microbial Populations in HIV/AIDS: α-Proteobacteria Predominate Independent of Host Immune Status. PLoS ONE 8(1): e54673. doi:10.1371/journal.pone.0054673

Abstract

The brain is assumed to be a sterile organ in the absence of disease although the impact of immune disruption is uncertain in terms of brain microbial diversity or quantity. To investigate microbial diversity and quantity in the brain, the profile of infectious agents was examined in pathologically normal and abnormal brains from persons with HIV/AIDS [HIV] (n = 12), other disease controls [ODC] (n = 14) and in cerebral surgical resections for epilepsy [SURG] (n = 6). Deep sequencing of cerebral white matter-derived RNA from the HIV (n = 4) and ODC (n = 4) patients and SURG (n = 2) groups revealed bacterially-encoded 16 s RNA sequences in all brain specimens with α-proteobacteria representing over 70% of bacterial sequences while the other 30% of bacterial classes varied widely. Bacterial rRNA was detected in white matter glial cells by in situ hybridization and peptidoglycan immunoreactivity was also localized principally in glia in human brains. Analyses of amplified bacterial 16 s rRNA sequences disclosed that Proteobacteria was the principal bacterial phylum in all human brain samples with similar bacterial rRNA quantities in HIV and ODC groups despite increased host neuroimmune responses in the HIV group. Exogenous viruses including bacteriophage and human herpes viruses-4, -5 and -6 were detected variably in autopsied brains from both clinical groups. Brains from SIV- and SHIV-infected macaques displayed a profile of bacterial phyla also dominated by Proteobacteria but bacterial sequences were not detected in experimentally FIV-infected cat or RAG1^−/− mouse brains. Intracerebral implantation of human brain homogenates into RAG1^−/− mice revealed a preponderance of α-proteobacteria 16 s RNA sequences in the brains of recipient mice at 7 weeks post-implantation, which was abrogated by prior heat-treatment of the brain homogenate. Thus, α-proteobacteria represented the major bacterial component of the primate brain’s microbiome regardless of underlying immune status, which could be transferred into naïve hosts leading to microbial persistence in the brain.

Figure 1. Deep sequencing detection of bacterial and bacteriophage RNA sequences in human brain.

(A) Total sequence tags that were unambiguously identified as belonging to a bacterial phylum were grouped for each patient from which the percentages for each phylum were displayed. All patients showed a predominance of Proteobacteria-associated sequences. (B) Despite inter-individual variability the mean percentage of Proteobacteria sequences among the HIV, ODC and SURG groups was similar. (C) The majority of bacterial sequences identified in all patient samples belonged to the Proteobacteria phylum, which showed the greatest similarity to the α-proteobacteria class. (D) The majority of bacteriophage sequences identified matched Proteobacteria-tropic phage sequences although bacteriophage sequences were not detected in the SURG samples. doi:10.1371/journal.pone.0054673.g001

My talk at the University of Illinois at Urbana-Champaign

Earlier this week I had the pleasure of visiting The House that microbiologist Carl Woese Built - The University of Illinois at Urbana-Champaign. With nearly a 100 evolutionary biologists and ecologists along with National Academy Members sprinkled across the integrative departments, its a wonder world of life sciences research. Indeed, famed virus hunter Nathan Wolfe happened to be visiting the campus the same day.

Here's my seminar on The Hologenome / Speciation by Symbiosis (Part I: 0 to 31:20) and Microbial Genome Evolution (Part II: 31:20 to Q&A). I usually am hypercritical of my own talks and find all sorts of things wrong with them. This seminar is perhaps the one time that the talk went off without a hitch. I even landed a few laughs with a joke on hybrid lethality (phew).

Related blog posts:
1. The story behind Speciation by Symbiosis? (April 26, 2012)
2. Is the microbiome part of the organism or the environment? (May 11, 2012)
3. Is the microbiota species specific? (June 23, 2012)

4. ASM's "Small Things Considered" spotlights the Speciation by Symbiosis article (August 16, 2012)

Darwin Day

Yesterday was a mild victory for promoting science, reason, and the future in the United States. Congressman Rush Holt (D-NJ) introduced a resolution to declare February 12th, DARWIN DAY, in honor of the 1809 birthday of one of the greatest scientists.  Sadly, this resolution will not make it far, I fear, but change in government happens by small steps. This motion, coupled with the enacted Golden Goose Award introduced by Nashville's own Jim Cooper to honor federally funded research (my blog post on its origin), are steps that should give us hope.

Here's a very short video of Rep. Holt's introduction of the Darwin Day resolution. It may just energize you a little bit more today. It did for me.

Part IV: Thoughts on Survival/Success in the New Era of Academia

Here is the last installment of tweets on this theme folks. Hope they've been of some help. Id like to pivot you to Josh Drew's blog post this week on the same theme. He has some things that just need be said more often. Here's an excerpt.

However, it occurs to me that the majority of the tasks I do ever day I have had very little to no formal training in. In a given week I 1) teach, 2) advise students, 3) apply for funding, 4) do research, 5) manage a graduate program and 6) write.  Now here’s the crux getting a Ph.D. is actually fairly poor preparation for the majority of these activities. 

In my case, I recall explicitly asking for a course on grantsmanship in graduate school. The idea was generally scoffed at, for reasons that I can only speculate as a cultural one. What is noteworthy is that in this new era of academia with limited federal funding, we are all getting more serious about what we do, who we train, and how we train them. This shift is part of the good in what can seem to be a troubling pattern in science funding.

1/27/13: If Life is the greatest show on earth, then biologists get to be at the circus for their entire career #tosrb #hallelujah

1/29/13: Scientists almost never get career breaks; They work hard & persevere in the face of doubt. Recognition comes retroactively #tosrb #Woese

1/29/13: Excellent training of students requires honesty to them, even when its hard. Excellent learning requires being honest w yourself #tosrb

1/30/13: When giving a seminar/lecture of excellence, remember to inspire regularly. Engagement is the button that turns on self-illumination #tosrb

2//13: EXPLORE not where your field is now, but where it is going to be in 3 years. It will transform and transcend you in your endeavors. #tosrb

Part III - Thoughts on Success/Survival in the New Era of Academia

Third installment...for background see previous two blog posts.

Thoughts on Success/Survival in the New Era of Academia Part I
Thoughts on Success/Survival in the New Era of Academia Part II

1/25/13: Biology PIs run small businesses too. Our labs must be well managed and produce a product that is sold to the granting agencies #tosrb

1/25/13: So much of attaining excellence is the confidence and courage to simply try. Anything less is a prescription for status quo #tosrb

1/25/13: Imagine a future in which you better engage your students or solve bigger questions - now pull that future forward to right now #tosrb

1/26/13: 6 NIH grants or 10 NSF grants is a career's worth of research. You dont got many chances to spur a paradigm. Choose wisely #torsb

1/26/13: PIs must give equal time to broadcasting and receiving info with students. I do this because my students are smarter than me #tosrb

Part II - Thoughts on Survival/Success in the New Era of Academia

Yesterday, I started Part I of a blog post series on survival/success tips for the new era in Academia.  My hope is that I can pass on some insight to those that are just beginning their careers - from students to new PIs. By doing so, by coaching through accrued wisdom, together we can speed up the pace of excellence in science for future trail blazers, rather than wait for people to learn these things themselves over a long career. 

As noted, I will post several of these tweets on a daily basis. Red highlights indicate ones that I think rise about the rest. As always, comments and questions are encouraged!

1/24/13: Students must recognize that they will be pushed to the brink, because their PIs know better than them how far they can go #tosrb

1/24/13: Letting go of limitations is part of the journey to excellence, for students and colleagues alike. Academics should heed this. #tosrb

1/24/13: I can't or I don't or I'm not are words that we should never ever use. We hide the gift of new knowledge for humanity if we do #tosrb

1/24/13: Science is the noblest of occupations for it discovers new truths. And that discovery is driven by 20-something's. Remarkable #tosrb

1/24/13: Education is the sibling of science for without it we can not build a family of humanity that sustains itself #torsb


Thoughts on Success/Survival in the New Era of Academia Part I

Thoughts on Survival/Success in The New Era of Academia - Part 1

Considering what has transpired in my career thus far and its still a career in its early phases, I have accrued just a few nuggets of wisdom that are useless if they are not shared. Let's start with the obvious. A career in the life sciences has its bountiful share of stress, which can frequently limit passion. Im not optimistic for the future of science if passion continues to dwindle for young scientists given the current funding climate. Take this observation for instance. Students in bio (red line) lose their interest in academic research jobs as they spend more time in grad school. Wow. Are PIs that bad at training their students to enjoy the job? Are we not taking in qualified enough students who can find strength through the struggles?

Citation: Sauermann H, Roach M (2012) Science PhD Career Preferences: Levels, Changes, and Advisor Encouragement. PLoS ONE 7(5): e36307. doi:10.1371/journal.pone.0036307

As a graduate student, I wished that I had a better idea of what it took to be successful in academia; I was told not to worry - that there would be plenty of jobs because the baby boomers would be retiring. That led to some false hopes. Fortunately, few students are being told this today. Not so fortunately, the latest stats indicate that 14% of life science phd land an academic job. As a postdoc, I wondered what it took to secure an academic job in a highly competitive environment. What was I supposed to do different than grad school? As a beginning investigator, I wondered how to get funded? This happened to be right around the time federal funding percentages were plummeting to historical lows (whoops). I wrote six grants before I got my first NSF grant. The answer to all these questions is the same. DO NOT TAKE NO FOR AN ANSWER. Perseverance is what make the difference. We can persevere if we imagine what excellence is and pull our future forward to meet that excellence. Excellence is always ahead of us and can always be attained by any of us. Just dont give up.

Success, which is what we are talking about here, is a state of mind more than a thing. In this light, I started tweeting nuggets of wisdom under the Twitter hashtag #tosrb for thoughts of my initials. I have heard from some colleagues and students that these shots of insight are useful. That is my hope, that I can pass on some insight to those that are just beginning. By doing so, by coaching through accrued wisdom, we may speed up the pace of excellence in science for future trail blazers, rather than waiting for people to learn these things themselves over a long career. 

Over this coming week, I will post several of these tweets on a daily basis. Red highlights indicate ones that I think rise about the rest. As always, comments and questions are encouraged!

1. 1/23/13: If u dont train your students to be better than u, then u are failing them and the society who benefits from future scientists #tosrb
2. 1/23/13: Most grad students transform in grad school. Fewer transcend. 14% ultimately get academic jobs. We need to talk about why. #tosrb
3. 1/23/13: Grad school is not a right of passage once students enter it, but rather the beginning of a 5 year boot camp. No guarantees at end. #torso
4. 1/23/13: Only 14% of life science PhDs in US get tenure track jobs in comparison to 55% of law students becoming lawyers. Change is needed #tosrb
5. 1/24/13: PI's must recognize that any recognition imparted to them is because of their students. Anything else is a failure in leadership #tosrb