Category Archives: bacteria

On The Ecosystem Within (UPDATE)

My last post was concerned with the way mice regulate the set of bacteria which reside in their intestines. Which specific bacteria are present in one’s gut is known to be predictive of obesity, but new research suggests that it isn’t the bacteria themselves that are important so much as the genes that they carry1.

Scientists at Washington University in St. Louis studied the bacteria present in the intestines of pairs of twins (a useful methodology for exploring many kinds of similarities amongst individuals with similar genes) and their mothers, expecting to find that those who were obese would have similar species of gut flora (similarly expecting comparable special cross-sections in those who were not obese). Interestingly, they found that the set of bacteria differed widely, but that the core “bacteriome” (the set of all the genes in all the bacteria in a person’s gut) was highly conserved across the obese (and separately across the non-obese). They further found that related individuals were more likely to harbor the same set of species.

This is not incredibly surprising. After all, the functional utility – in terms of digestive assistance, molecular synthesis, and nitrogen uptake – of these bacteria is defined by their genes. That is to say, bacteria can only be useful to us and our internal environment in that they are in possession of metabolic pathways that we lack. Furthermore, given the massive number of bacterial species, it is unsurprising that one person gets a specific part of the benefits from species A, while another person obtains that benefit from species B. It is a happy surprise to me that this research is progressing at an increasing pace. I hope it continues as such.

References:
1. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI. A core gut microbiome in obese and lean twins. Nature [Epub ahead of print], 2008.

On The Ecosystem Within

BIOMED. IMAGING UNIT, SOUTHAMPTON GEN. HOSP./SPL

There are more microbial cells than human cells in your body; this is a good thing. Bacteria help us break down foodstuffs by fermentation, synthesize vital molecules, and help us get rid of excess nitrogenous wastes. Furthermore, it has been demonstrated that the kind of bacteria you have in your gut is predictive of obesity: the right bacteria can help keep you thin1, 2. Thus, it is important to have a source of good microbes in your diet, like yogurt or kombucha (a fermented tea drink rich in microbes), especially if you’re engaging in activities that tend to kill off these organisms, like drinking heavily or taking antibiotics which don’t discriminate between the good & the bad bacteria.

While drugs may not be able to discriminate between good and bad bacteria, our bodies must be able to in order to maintain intestinal homeostasis; how this happens has been unclear, to-date. However, new research demonstrates how one type of “bad bacteria” – the so called gram-negative strains – are selectively targeted by the body’s immune system3. These microbes present an excess of a type of molecule on their membranes (peptidoglycans) which the body recognizes. The detection of these molecules causes the body to generate lymphatic tissue that specifically targets these bacteria.

As we come to understand more and more about the relationship between gut flora and health in general, this type of research will prove invaluable because it facilitates our understanding of the body’s innate ability to regulate the subset of flora residing within. In other words, there is surely a gradient of immune system function such that some individuals are better able to select which flora to keep and which to oust; understanding how the body achieves this feat will thus widen the scope of western medicine.

References:
1. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444: 1027-1031, 2006.
2. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 444(7122):1022-1023, 2006.
3. Bouskra D, Brézillon C, Bérard M, Werts C, Varona R, Boneca IG, Eberl G. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456: 507-510, 2008.

On Quorum Sensing and Antibiotics

In your body, cells belonging to other organisms are more numerous than your own1. Most of these are not parasitic, we benefit significantly from some of our inhabitants. This is one of the reasons that traditional antibiotics are potentially harmful. Their action is indiscriminate, targeting both harmful and helpful bacteria. The wholesale killing off of our microbial boarders makes many vacancies, providing an opportunity for more virulent creatures to invade. As if this weren’t bad enough, left behind after a course of antibiotics are any bacteria that might have developed immunity to the drugs that put down their brethren. Thus, prescribing such medications also amounts to a selective pressure, an evolutionary nudge towards ever stronger infectors.

Once in your body, harmful bacteria must wait until their colony reaches a certain size for their attacks to be effective. This means that they must posses the ability to detect how many individuals of their species are present. Indeed, this behavior has been the subject of extensive research, and is referred to as Quorum Sensing (QS). The way this works is actually rather simple, each bacterium secretes a small molecule called an autoinducer (AI) at an approximately constant rate (in time and across individuals). Once the concentration of AI is high enough, the colony knows their population has risen to a level where the release virulence factors stands a good chance of successfully inducing pathology.


from reference 2

This example of cell-to-cell communication, in addition to providing a unique system to study such information transfer systems, presents an opportunity to attack unwanted microorganisms in a more species selective way. Thus avoiding both of the issues with antibiotics mentioned above.

Just such a feat was accomplished several years in the laboratory of Hiroaki Suga at SUNY Buffalo. This team of researchers was able to successfully reduce the virulence of Pseudomonas aeruginosa which is the main infectious killer of those with weakened immune systems, such as cancer, AIDS, and cistic fibrosis patients3. This was a great triumph, but another entry in this category has come along which further bolsters the case for attacking the bacterial-telegraph-system.

A group led by Kim Janda at Scripps was able to have a similar impact on Staphylococcus aureus. This bacteria is the main cause of infections in hospitals, and thus represents one of the strains most likely to evolve immunity to antibiotics4. Beyond this and in contrast to the earlier work, these authors were able to use antibodies to target the AIs, making the work potentially generalizable and inexpensive.

It is impossible to understate the beneficial effects that penicillin and it’s derivatives have had in western medicine. As we move forward, however, we must find ways to keep pace with our miniscule counterparts. These two examples of top notch research are exactly the kind of thinking that we need.

References

1. French, K. Randall, D & Burggren, W. (2001) Eckert Animal Physiology. W.H. Freeman

2. Waters, C.M. & Bassler, B.L. (2005) Quorum Sensing: Cell-to-Cell Communication in Bacteria. Annu. Rev. Cell Dev. Biol. 21:319–446

3. Smith, K.M. Yigong, B. & Suga, H. (2003) Induction and Inhibition of Pseudomonas aeruginosa Quorum Sensing by Synthetic Autoinducer Analogs. Chemistry & Biology 10:81-89

4. Park, J. Jagasia R. Kaufmann, G.F. Mathison, J.C. Ruiz, D.I. Moss, J.A. Meijler, M.M. Ulevitich, R.J. & Janda, K.M. (2007) Infection Control by Antibody Disruption of Bacterial Quorum Sensing Signaling. Chemistry & Biology 14:1119-1127

On Bacteria & Wiring

All known living things harvest high-energy electrons from hydrocarbons for power. Those creatures which reside in oxygen rich environments pass these waste electrons to oxygen while those that live near geothermal vents use sulfur as their dustbin.

(Shewanella oneidensis from ref. 1)

The bacteria pictured above, however, have access to neither. They live in minimal-sulfur soil at a depth where oxygen is unavailable. Instead, they pass their low-energy electrons to metals, readily available conductors in the earth. The idea that a metallic element may be substituted for something as “fundamental” to life as oxygen is food for the imagination. Beyond this, however, is an even more contentious concept. As you can see from the image, these bacteria produce nanoscale structures resembling wires. Furthermore, it has been demonstrated that these filaments conduct electricity (ref. 1). The researchers who demonstrated this fact believe that the bacteria are using their nano-wires to transport their electrons over long distances to the surface oxygen, creating a current source in the dirt.

This claim is by no means proven, but it is intriguing that the suggestion hasn’t even been considered until now. Also, the implications of an electrically connected community of bacteria are significant. Microorganisms have presented many examples of behaviors normally thought to be reserved to higher animals, and if the authors responsible for this work turns out to be true, studying the dynamic interactions of these communities has the potential to teach us about systems of electrically coupled cells like our brains. Taking speculation to the extreme, one might ask whether these creatures could constitute a biological-battery, yielding electricity for our own use.

References

1. Y. A. Gorby et al. (2006) Electrically conductive bacterial nanowires produced by Shewanella oneidensis strain MR-1 and other microorganisms Proc. Natl Acad. Sci. USA Vol. 103, pp. 11358–11363

2. Jestin JL, Kaminski PA. (2004) Directed enzyme evolution and selections for catalysis based on product formation. J Biotechnol. 113(1-3):85-103