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*Image taken from the public domain.
A new type of bacteria that can only survive with caffeine

If you think you have seen it all, this blog entry will blow your mind. Researchers from the University of Austin, Texas, engineered a strain of Escherichia coli that can only survive with caffeine. Yes, caffeine, the holy grail of graduate students. But, why in the world would someone want to engineer a microorganism that would be capable of metabolizing caffeine? It turns out that, with the continuous growth of pharmaceuticals and other industries all around the world, there is an increase of caffeine as a pollutant in the water and land around cities. So, it was necessary to develop a strategy that would help diminish the quantity of caffeine from the environment.

As weird as it seems, nature had a way of solving this pollution crisis. The recently discovered bacteria, Pseudomonas putida CBB5, was found to be able to metabolize caffeine in the environment. By analyzing the metabolic network of P. putida CBB5, researchers discovered which enzymes were necessary for digesting caffeine. So, they used this information to engineered E. coli in a way that it can produce the enzymes that are necessary for metabolizing caffeine.

There you have it. In the future,  we could be able to use these bacteria to produce decaffeinated beverages, in addition of cleaning the environment. Could these new discoveries benefit the Caffeine Beverage Industry? Who knows...



*References:
(1) http://www.popsci.com/science/article/2013-03/bacteria-caffeine-addict-its-possible
 
Picture
*Image from the public domain
The secret of bacterial alchemists

As taken from a fantasy novel, nature surprises us one more time with a marvelous story. This is the case for two species of bacteria, the extremo-philes Cupriavidus metallidurans and Delftia acidovorans. Using a metagenomics approach, researchers from the University of Adelaide, discovered these two species of bacteria forming biofilms on the surface of gold grains from a mine in Queensland, Australia. What is interesting about these two species is that they are capable of transforming liquid gold, in the form of the toxic gold chloride, into solid 24-karat gold. Yes, in pure solid gold.

One of the most precious and expensive materials in our planet can be transformed from a liquid form to a purer solid state by bacteria.
And not just that, these bacterial species were also found to dissolve gold grains into nanoparticles that move through rocks and crevices, thus contributing to the movement of gold around the environment. In addition, this natural phenomenon contradicts the belief that gold can only be formed through physical geological processes.

This unprecedented alchemical process had fascinated scientists all around the world due to its unique nature. Who would have thought that microorganisms could be capable of transforming gold to a pure solid state? Once again, nature has shown us how surprising is our planet. I am certain that, in a near future, microbes will surprise us once again with an incredible discovery. That is why I am counting on metagenomics as a tool to expand our knowledge in this microbial planet that we live in.

*References:
(1) Bacteria Make Gold Nuggets, Discovery Magazine
(2) Gold-Loving Bacteria Show Superman Strength, Michigan State University News
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*Gold granules produced by the bacterium Cupriavidus metallidurans. Photo by G.L. Kohuth. Taken from the work of Adam W. Brown and Dr. Kazem Kashefi, Michigan State University.
 
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*Olavius algarvensis | Image from C. Lott/ HYDRA/ Max Planck Institute for Marine Microbiology, Bremen.
A poisonous food for a gutless animal

In the sandy sediments off to the coast of the Mediterranean island of Elba in Tuscany, Italy, resides an amazing oligochaete wormOlavius algarvensis. This marine worm is very peculiar because of its anatomy and physiology. What is interesting of this animal is that it completely lacks a digestive tract; no mouth, no stomach, no intestines. However, it remains as a very functional animal within its ecosystem. But what is weird of this marine worm is that its diet is composed of very toxic compounds like carbon monoxide and hydrogen sulphide. So, how in the world, an animal with no digestive tract can survive by consuming solely toxic compounds? It turns out that a group of bacteria is responsible for their nourishment, their waste management, and their survival.

Knowing how the endosymbiotic bacteria help nourish and maintain the nutrition demands of this marine worm was a mystery for scientists around the world. However, on 2006, a group of scientists from the U.S. Department of Energy Joint Genome Institute (JGI), in collaboration with other institutions, published a paper in which they described, using a metagenomics approach, how outsourcing energy and waste management was maintained in the marine worm by their endosymbiotic bacteria. Their goal was to obtain all the genomic content of the endosymbiotic bacteria that resided in all the body parts of the marine worm Olavius algarvensis. After shotgun sequencing of the genomic data of all the metagenomes of the bacteria that resided within O. algarvensis, they were able to identify genes that had a functional role in metabolic pathways that were involved in management of waste products and energy outsourcing. Their analysis revealed how dependent marine worms were from their endosymbionts. Nevertheless, they found evidence suggesting that their symbiotic bacteria are not obligate host-dependent and could survive outside the host in a free-living stage.

This study was of important value to science, specially to symbiosis research because it was the first instance in which a metagenomic shotgun sequencing approach was used to study mutualistic interactions between bacteria and their host. With studies like this,  we can learn more about successful strategies of adaptation that many animals have in our planet.
 
Don't forget to watch the video at the end of this blog entry!
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*Fluorescence in situ hybridization of endosymbionts in O. algarvensis. Obtained from Dubilier et al. (2001) Nature
 
Picture*Image of A. gambiae from Dr. Larry Zwiebel lab, Vanderbilt University
Skin bacteria contribute to the mosquitoes' attraction towards humans

In a sense, we all smell different. Every human being has a particular scent that is perceivable among others. Some persons have strong odors while others have more delicate odors, and so forth. However, what is interesting about human scent is that our skin alone, is not capable of emitting any odor, so in theory, we should be odorless (for more information about this topic, follow this link). But the question is, why do we smell? It turns out that there are groups of bacteria that live throughout our bodies, specifically in our skin that produce volatile compounds that give a scent. This mixture of volatile compounds is what we perceive as our body odor, which is particular to specific areas of our body. But do not get alarmed, after all, we are holobionts, which means we live in close interaction with millions of microorganisms from the moment we are born (for more information about the microbes that first colonize our bodies follow this link) until the moment we perish, and more importantly, they are necessary for our survival.

What does any of this have to do with mosquitoes? Well, as a matter of fact, mosquitoes are experts in detecting smell, and it turns out, we produce their favorite smell. Actually, our skin bacteria produce their favorite smell. That is one of the reasons they can easily detect us, no matter where we are. Interestingly enough, there are persons that are more attractive to mosquitoes than others. The reason to this selective attraction lies in the types of microbes that are abundant within your skin microflora. In a recent study, scientists from Wageningen University and Research Centre in the Netherlands discovered that Malaria mosquitoes (Anopheles gambiae) have a differential attraction to volatile blends produced by specific groups of bacteria associated to the skin of humans (Verhulst et al. 2010). In other words, there are specific groups of bacteria in our skin (which, essentially, are part of our normal skin microflora) that produce compounds that are irresistible to mosquitoes. They identified 4 major groups of bacteria that had a huge impact in the mosquitoes attractiveness. Persons that had a great deal of Corynebacterium minutissimum, Brevibacterium epidermidis, Bacillus subtilis, or Staphylococcus epidermidis in their skin were more attractive to mosquitoes while persons that had more Pseudomonas aureginosa, Leptotrichia, and/or Delftia species were less attractive (for more information about these findings, follow this link). So, if you think you are sweet for mosquito bites then it is probable that you have an abundance of one of the 4 groups of bacteria mentioned above.

These findings are of important value for further studies that are involved in eradicating malaria and other diseases transmitted by mosquitoes. Once we understand the interactions between mosquitoes that are vectors of different types of pathogens (i.e. Dengue, Yellow Fever, Malaria), and the way they're are attracted to humans, we can start developing chemicals that attract mosquitoes to traps or ways to repulse the insects from us. At least we are still in the race that aims to eradicate malaria, and it appears we are winning.

*References:
(1) Verhulst, N.O., et al. (2010) Chemical ecology of interactions between human skin microbiota and mosquitoes. FEMS Microbiol Ecol 74: 1–9.
(2) Verhulst, N.O., et al. (2010) Differential attraction of malaria mosquitoes to volatile blends produced by human skin bacteria. PLoS One 5(12): e15829.
(3) Verhulst, N.O., et al. (2011) Composition of human skin microbiota affects attractiveness to malaria mosquitoes. PLoS One 6(12): e28991.

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*Image obtained from the History of Medicine Collection (NIH)
 
Picture*Image taken from Cho and Blaser (2012) Nature Reviews Genetics
Delivery mode impacts newborn's microbiota

With the advancement of Next Generation Sequencing (NGS) techniques, many microbiologists are now able to study in depth the microbial communities within environments of great interest to human health. This is the case for microbiologist Dr. María G. Domínguez–Bello of the University of Puerto Rico-Río Piedras. In 2010, she and her colleagues published an article in which they characterized the bacterial communities of different parts of the body of human babies immediately after they were born (< 5 min), thus contributing in the understanding of the initiation stage of human microbiome development (see figure above for more information about this topic). The interesting part of her work was that she compared the bacterial communities of babies that were born through vaginal delivery vs. those born through cesarean section. Her discovery was remarkable. Not only she demonstrated that newborn babies have undifferentiated bacterial communities across different body habitats but that the composition of such communities is directly correlated to the delivery mode of birth of the infant. Babies that were born through vaginal delivery had a bacterial signature similar to that of their mother's vagina, in which Lactobacillus and Prevotella species dominate. In contrast, babies born through cesarean section showed a bacterial signature similar to their mother's skin (specifically the ventral side of the mother's forearms), in which Staphylococcus species dominate (see figure below for more details).

Picture*Figure taken from Domínguez-Bello et al. (2010) PNAS.
The trajectory of neonatal gut microbiota of human babies from the moment they are born until they reach 27 months of age.

In addition to the mode of delivery, the microbial communities that colonize the human body throughout the first stages of development (after birth) are greatly influenced by a variety of factors [see the work of Cho and Blaser (2012) for more information]. Interestingly enough, the succession patterns of microbial communities within the gut of human babies show a compositional shift in the abundance of major bacterial taxa over time (Koenig, et al. 2011). This compositional shift can be appreciated in the video below. This video was developed by members of Dr. Rob Knight's lab at the University of Colorado-Boulder. The trajectory that is well illustrated in the video was created from data published by Koenig et al. (2011) and framed against data  generated by the Human Microbiome Project (HMP). From the video, you can see that the pattern of succession of the neonatal microbiota shifts from a vaginal-like composition at birth to an adult gut-like composition after 27 months of age.




*References
(1) Cho, I., and Blaser, M.J. (2012) The human microbiome: at the interface of health and disease. Nature Reviews Genetics 13: 260–270.
(2) Domínguez–Bello, M.G. (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 107(26): 11971–11975.
(3) Koenig, J.E. et al. (2011) Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A. 108(suppl. 1): 4578–4585.


 
Picture*Image from redOrbit.com
All hail to the computer scientists and their bioinformatics tools!

Let's say you are now ready to analyze your sequencing data. However, you have no idea what bioinformatics tools are available and which ones are the most convenient to use for your specific experiments. Well, if you didn't realize this before, it would be better for you to know that metagenomics is a field that is more suitable for the people that are savvy in computer languages or with experience in bioinformatics tools. But, don't let this get you down. There is still time to acquire skills in computer sciences, and you can even have fun during the process (for more information regarding computational tools that are useful for solving biological problems, visit this link).

Now, in relation to the metagenomic sequences, there are many options available that you can use for analyzing your data. The approach that you decide to use will depend greatly on your research objectives, and in the questions you want to answer. With this in mind, it is important that you understand some of the experimental and computational steps you have to cover during the acquisition and analysis of your data.

Below is a diagram that illustrates the experimental and computational steps that are necessary for a metagenomics study:


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*Diagrams were modified from Thomas, et al. (2012), and from Angly, et al. (2009).
Houston, we have a solution!

In the brink of desperation, when nothing works and you have no clue whatsoever of what bioinformatics tools are available and which ones are the right ones to use for your experiment, there is still a chance for not letting anxiety take the best of you. Many bioinformaticians around the world are working in the development of better tools for analyzing genomic data. You can access some of these computational tools  by clicking the items on the list below:
  • Metagenomic sequence pre-filtering
          – Eu-Detect
          – DeconSeq
  • Metagenomic-specific assembly
          – Meta-IDBA (de Novo assembler for metagenomic data)
          – MetaVelvet (de Novo assembler for metagenomic data)
          – Celera Assembler
          – Newbler
          – Genovo
          – Phrap          
          – MAP (Metagenomic Assembly Program)
          – MetAMOS
  • Assembly quality evaluation
          – Gage
          – QUAST
  • Metagenome analyzers (Gene prediction)
         – MEGAN 4
         – GeneMark
         – GLIMMER
  • Metagenomic and/or profile species diversity analysis
         – QIIME
         – PhymmBL
         – MetaPhlAn

These and other tools are still available online and most are open-source. If you are interested in this topic and want more information about these computational approaches for analyzing your metagenomic data, I'll recommend that you take a look at the Metagenomics Informatics Challenges Workshop 2011 organized by the US Department of Energy Joint Genome Institute (JGI). In this series of talks, scientists discussed the capabilities and advantages of some of the computational tools that I mentioned in the list before. All the talks from the workshop are now available on YouTube. In the video below, you can watch the introductory talk to these workshops.


Good luck on your analysis!

*References:
(1) Angly et al. (2009) The GAAS metagenomic tool and its estimations of viral and microbial average genome size in four major biomes. PLoS Comput Biol. 5(12): e1000593.
(2) Hamady, M., and Knight, R. (2009) Microbial community profiling for human microbiome projects: Tools, techniques, and challenges. Genome Res. 19: 1141–1152.
(3) Kalyuzhnaya, M.G. et al. (2008) High-resolution metagenomics targets specific functional types in complex microbial communities. Nature Biotechnology 26(9): 1029–1034.
(4) Kunin, V. et al. (2008) A bioinformatician’s guide to metagenomics. Microbiol. Mol. Biol. Rev. 72(4): 557–578.
(5) Simon, C., and Daniel, R. (2011) Metagenomic analyses: past and future trends. Appl. Environ. Microbiol. 77(4): 1153–1161.
(6) Thomas et al. (2012) Metagenomics- a guide from sampling to data analysis. Microbial Informatics and Experimentation 2:3.
(7) Wooley, J.C., and Ye, Y. (2009) Metagenomics: facts and artifacts, and computational challenges. J Comput Sci Technol. 25(1): 71–81.
(8) Xu, J. (2006) Microbial ecology in the age of genomics and metagenomics: concepts, tools, and recent advances. Molecular Ecology 15: 1713–1731.
 
Picture* Image from Cho and Blaser (2012) Nature Reviews Genetics
A catalogue of microbes in the human gut

It comes to my attention how our knowledge of the microbial world is rapidly expanding throughout the years. As of today, researchers are able to identify most of the microorganisms that inhabit a specific environment in an ecosystem, including parts of our bodies (see image on the left). Now is known, that the set of microbes, their genomes and their environmental interactions that are associated within our bodies (here forth termed as the human microbiome) have an important role in human health. This is reason of why many scientists around the world are paying attention to microbes and their role in diseases and other medical-related conditions.

The human microbiome project was developed with the purpose of understanding all the microbial communities (including their genomes and their interactions) that are associated to humans. Their aim, as is presented on their website, reads as follow:


"The aim of the HMP is to characterize microbial communities found at multiple human body sites and to look for correlations between changes in the microbiome and human health."
Picture*Figure from Qin, et al. (2010) Nature
In addition to the human microbiome project, researchers from Europe and China collaborated to develop the MetaHit (Metagenomics of the Human Intestinal Tract) project. This project lasted from 2008 – 2012, and with it, many scientific discoveries were published (look video below for more information about the project). Among those discoveries, it is worthwhile to mention the work of Qin, et al. (2010) from the MetaHIT Consortium, about the human gut microbial gene catalogue.

In this article, using deep metagenomic sequencing, the authors managed to identify and characterize a catalogue of microbial genes (encoded in their metagenomes) that were present in the gut of individuals with obesity/diabetes phenotypes, patients with Crohn's disease or ulcerative colitis, and healthy individuals. They were able to study these metagenomes due to the power of the new emerging sequencing technologies. Their results showed that the microorganisms that predominated in the gut of the individuals that were studied belong to the phyla Firmicutes and Bacteroidetes. In addition, they noted a significant difference in the species abundance of the core microbiota of healthy individuals and patients with Crohn's disease or ulcerative colitis (figure shown above). These results might suggest a possible role of specific microbial species in the progression of inflammatory bowel disease in patients suffering from such diseases.

With the advancement of these sequencing technologies, we could easily predict how medicine will change in the near future. With years to come, and as long as technologies continue to grow, we might be able to diagnose and medicate patients individually according to their genomic and metagenomic background. In this way, treatments could be more specific and more accurate, leading to a better diagnosis and a faster recovery.


*References:
(1) Cho, I., and Blaser, M.J (2012) The human microbiome: at the interface of health and disease. Nature Reviews Genetics 13: 260–270.
(2) Qin, J., Li, R., Raes, j., et al. (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464(4): 59–67.

 
Picture*Image from clinical-bioinformatics.com
Next Generation Sequencing (NGS) technologies to the rescue!

It wasn’t long ago when sequencing genomes were a very expensive and tiresome procedure. Nowadays, with the emergence of Next Generation Sequencing (NGS) technologies (for more information regarding these technologies, visit the following link), we are able to test many biological problems that were nearly impossible to work with in past years.

These technologies had also contributed in the development of new areas of research that followed, in close range, the omics movement. Genomics and more recently metagenomics fields emerge from the application of these technologies. Since these new approaches became readily available, scientists all over the world took advantage of these NGS technologies and began doing novel research in different areas of biology that resulted in surprising discoveries. One of these scientists was Dr. J. Craig Venter, a famous North American biologist and entrepreneur. In addition to his outstanding contributions in the determination of all the sequences in the human genome (see human genome project), he pioneered in using NGS technologies as a mean for cataloguing the metagenomes of millions of microbial species in different marine environments (see video below). As a result, he was able to determine the tremendous microbial diversity that dominated such marine environments, and he could also identify a vast collection of microbial genes with possible roles in metabolic pathways and with importance to the ecosystem (for more information see Venter, et al. 2004).

As NGS technologies continues to grow, new approaches for studying microorganisms will become available. To me, it would not be surprising if in the near future we encounter that our microscopic friends happened to be involved in important processes in the development and evolution of organisms. These new discoveries could have a huge impact in our understanding of biological processes that could change our perception in how we study human diseases, such as cancer, inflammable bowel diseases, asthma, diabetes, etc. This is the reason of why we can not overlook the presence of microbes in any biological study.


*References:
(1) Venter, J.C., et al. (2004) Environmental genome shotgun sequencing of the Sargasso Sea. Science 304(5667): 66–74.

 
Bringing you closer to metagenomics!

I am very excited to know that you have selected (or are thinking in selecting) the field of metagenomics as a career path for your future. In this field, we strive to uncover and to reveal the secrets of our microbial planet. If you wish to explore more about this topic, I'll recommend that you read the book: "The New Science of Metagenomics", from the National Academy of Sciences (book cover image to the right). This book exquisitely explains the importance of this field.

Most of us graduate students often face with the unstable confusion of not knowing how to analyze metagenomics data. There are too many programs available on the internet, yet it is not cleared which ones are more fitted for our analysis. This is the time when we often succumb in an abyss of uncertainty, and our brains are more likely to explode.
Picture
*Image from National Academy of Sciences
Well my fellow Metagenomic adventurers, we all have been there at some point of our lives. Luckily, there is good news for us. There are many workshops, small technical courses, seminar series, and summer courses that are offered throughout the year at many institutions that can help you stay on the right track.

Here, I'll show you a list of some programs that are useful for training students, professors and professionals in analyzing metagenomic data.

1) Marine Biological Laboratories (MBL)
     – Summer Course in Microbial Diversity
        (usually lasts 6 weeks | Deadline: Early February of each year)
     – Special Topics in Strategies and Techniques for Analyzing Microbial Population

        Structures
         (usually lasts 11 days | Deadline: Early April of each year)
2) European Molecular Biology Laboratory (EMBL)
     – Practical course in Metagenomics: From the Bench to Data Analysis
        (usually lasts 1 week | It is scheduled during April)
3) EMBL–European Bioinformatics Institute (EBI)
     – Training course in Metagenomics: Managing, Analysing and Visualising Data
        (usually lasts 3 days | Deadline: July 12, 2013)
4) University of Oslo, Department of Biosciences
     – Course in Bioinformatics for metagenomic analyses and environmental

        sequencing
        (usually lasts 5 days | It is scheduled during March)
5) DOE Joint Genome Institute
     – Workshops in Microbial Genomics and Metagenomics
        (usually lasts 5 days | Scheduled throughout different dates, usually in February,

        May and September)

Well, there you have it. If you happen to know of other courses that are useful for microbiologists, please, let me know in the comment section.


Good luck on your analysis!
 
Picture*Image extracted from The National Academies
A microbial world indeed...

We live in a planet that is completely dominated by microorganisms. About half of Earth's total biomass is entirely composed of microbes, whereas animals just make up about 1/1000th of the biomass. So far, our knowledge of microbes is very limited and is very restricted to those microorganisms that play a role as pathogens to humans and other economically important organisms (e.g. farm animals, lab animals, agricultural plants, etc.).

With the emergence of Next Generation Sequencing (NGS) technologies, we can expand this knowledge and begin studying microorganisms at a larger scope.

Now is the time to embrace the microbiological sciences. Better yet, to make extraordinary discoveries about the function and role of microbes in every ecosystem. This is where NGS comes handy. High-throughput sequencing techniques are offering us the opportunity to study microbial communities at a large scale, in a field that is now known as metagenomics