A couple of weeks ago, Sdf Dsfds asked me to write something about my work on bacteria as multicellular organisms. I promised to do so after posting the blog about horizontal DNA transfer in animal evolution. The announcement of the UCS Center for Science and Democracy intervened, but now I can fulfill.
In the early 1980s, I was fortunate to observe that lab strain E. coli colonies are organized structures displaying spatially differentiated expression of their genomes. Each colony was a flower. This observation immediately told me that the bacteria grew as interactive populations capable of coordinating their activities.
In effect, bacteria are fundamentally multicellular and therefore possessed what had to be sophisticated intercellular communication systems. In 1988, I published a Scientific American article on the subject entitled "Bacteria as Multicellular Organisms". Nine years later, my University of Minnesota colleague Martin Dworkin and I edited a book with the same title.
The following year (1998), I published another review in a professional journal and used the opportunity to point out the immense variety of signaling molecules known at that time to regulate a wide range of bacterial properties: from motility, aggregation and DNA transfer to metabolism and bioluminescence. Bacteria truly had a large lexicon of chemical words for communicating with each other.
In the next to the last decade of the 20th Century, bacterial multicellularity was still controversial within the microbiology profession. The conventional notion of bacteria as "single-celled organisms" prevailed among my colleagues.
However, ever since the 1960s and 1970s, there has been steadily growing study of bacterial signaling. Moreover, close attention has been paid to how bacteria behave in nature, with particular emphasis on the human body.
All this research has led to a widespread appreciation in the 21st Century that bacteria generally grow in organized populations, frequently as structures called "biofilms." A biofilm is a thin colony spread out to cover a surface and held together by extracellular polymers (long, chain-like molecules).
As we would expect, the ability of bacteria to communicate by chemical signals and through direct cell contacts has a profound affect on how they organize themselves in biofilms and colonies. In other words, "sociobacteriology" is essential to understanding what bacteria do in the real world.
A particularly good example of how useful sociobacteriology can be is the work of my University of Chicago colleague, the abdominal surgeon Dr. John Alverdy. In the late 1990s, John was interested in the role of bacteria in post-surgical morbidity. Much of the inflammation and infection following an operation could not be explained by tissue damage alone, and there was evidence for a pathogenic role by normal intestinal bacteria.
At the time, the reigning idea was that surgical trauma leads to blood stream infection by pathogenic bacteria present in the gut. Knowing about my work, John started to look at this important clinical issue from a new, sociobacteriological perspective. He and his colleagues asked how bacterial biofilms behaved in the intestine during surgical injury and whether they were capable of hiding within biofilms. They studied this phenomenon in mice using the well-characterized opportunistic pathogenic bacteria of the species E. coli and Pseudomonas aeruginosa.
John's group has used the biofilm focus to carry out a remarkably successful series of studies over the past decade. Here is a list of the multicellular and interactive (communicational) features of bacterial action they have documented:
• Activation of bacterial cell-cell adhesion molecules;
• Involvement of diffusible bacterial intercellular signaling molecules that regulate biofilm formation (Wu, Holbrook et al. 2003);
• Identification of quinoline signaling molecules as a component of the bacterial interactions with endogenous opioids (Zaborina, Lepine et al. 2007);
• Response to diffusible signals produced by the host organism specifically following surgical trauma and not under normal conditions (Kohler, Zaborina et al. 2005);
• Identification of the human stress-signaling molecule HIF-1 (hypoxia-inducible factor) as a regulator, whose activation produces secreted signals sensed by biofilm-producing bacteria (Patel, Zaborina et al. 2007).
In addition to documenting the role of bacterial communication, adhesion and sensing in post-surgical morbidity, John's research has made it possible to identify factors that affect the bacterial response. This kind of research provides important clues for how to treat post-operative patients and how to identify treatments that may reverse post-op complications. The relevant findings include:
• Identification of high molecular weight polyethylene glycol (similar to antifreeze) as a non-toxic preventive agent that may be clinically useful (Wu, Zaborina et al. 2004);
• Pinpointing the role of dietary phosphate as an important factor suppressing biofilm virulence expression in Pseudomonas aeruginosa (Long, Zaborina et al. 2008);
• Identification of the pain-killer morphine as a potent signal recognized by intestinal bacteria that shifts them to express a lethal phenotype against the host during post-op trauma (Babrowski, Holbrook et al. 2012).
In other words, John's work is a model of what we now call "translational research" - that is, taking conceptual novelties, basic science observations, and "translating" them to useful findings in real-world clinical practice. I feel lucky to have played a small part in John's truly major accomplishments.
Babrowski, T., C. Holbrook, et al. (2012). "Pseudomonas aeruginosa virulence expression is directly activated by morphine and is capable of causing lethal gut-derived sepsis in mice during chronic morphine administration." Ann Surg 255(2): 386-393. http://www.ncbi.nlm.nih.gov/pubmed/21989372.
Kohler, J. E., O. Zaborina, et al. (2005). "Components of intestinal epithelial hypoxia activate the virulence circuitry of Pseudomonas." Am J Physiol Gastrointest Liver Physiol 288(5): G1048-1054. http://www.ncbi.nlm.nih.gov/pubmed/15550562.
Long, J., O. Zaborina, et al. (2008). "Depletion of intestinal phosphate after operative injury activates the virulence of P aeruginosa causing lethal gut-derived sepsis." Surgery 144(2): 189-197. http://www.ncbi.nlm.nih.gov/pubmed/18656625.
Patel, N. J., O. Zaborina, et al. (2007). "Recognition of intestinal epithelial HIF-1alpha activation by Pseudomonas aeruginosa." Am J Physiol Gastrointest Liver Physiol 292(1): G134-142. http://www.ncbi.nlm.nih.gov/pubmed/16901993.
Wu, L., C. Holbrook, et al. (2003). "Pseudomonas aeruginosa expresses a lethal virulence determinant, the PA-I lectin/adhesin, in the intestinal tract of a stressed host: the role of epithelia cell contact and molecules of the Quorum Sensing Signaling System." Ann Surg 238(5): 754-764. http://www.ncbi.nlm.nih.gov/pubmed/14578740.
Wu, L., O. Zaborina, et al. (2004). "High-molecular-weight polyethylene glycol prevents lethal sepsis due to intestinal Pseudomonas aeruginosa." Gastroenterology 126(2): 488-498. http://www.ncbi.nlm.nih.gov/pubmed/14762786.
Zaborina, O., F. Lepine, et al. (2007). "Dynorphin activates quorum sensing quinolone signaling in Pseudomonas aeruginosa." PLoS Pathog 3(3): e35. http://www.ncbi.nlm.nih.gov/pubmed/17367209.
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