Xi, C., & Wu, J. (2010). dATP/ATP, a Multifunctional Nucleotide, Stimulates Bacterial Cell Lysis, Extracellular DNA Release and Biofilm Development PLoS ONE, 5 (10) DOI: 10.1371/journal.pone.0013355
| SUMMARY: Pathogenic bacteria form dense protective aggregates in response to a physiological warning of their presence. |
From an evolutionary standpoint, it would make sense for pathogenic bacteria to have their own response to this biochemical danger signal, to stay one step ahead of the immune system. Chuanwu Xi and Jianfeng Wu (University of Michigan, United States) have found such a response; specifically, assembly into bacterial biofilms.
Bacterial biofilm assembly: So what?
What's a bacterial biofilm, and why should anyone care what causes them to form? Bacterial biofilms are dense packings of bacterial cells, especially important to medicine because such assemblies are highly resistant to antibiotics.
Biofilms are thought to be a leading cause of infections acquired at the hospital, and are likely a major reason why implanted medical devices eventually fail. One ordinarily can't counteract biofilms by simply increasing the amount of antibiotics given to the patient, due to toxicity issues, a fact that has inspired the development of nontoxic antibiofilm drugs.
Clearly, defeating bacterial biofilms is highly relevant to human medicine. Understanding what causes bacteria to assemble into such structures may lead to medical treatments aimed at disrupting them or counteracting their initial assembly.
Bacterial response to a biochemical danger signal.
The scientists first found that adenosine triphosphate, at a concentration of 400 micromolar, induces Escherichia coli bacteria to form dense biofilms on a glass microscope slide. The biofilms are approximately 50% more dense than when adenosine triphosphate is not present (the control experiment).
The rate of bacterial growth is unaffected, and treating the cells with apyrase (an enzyme that also reacts with adenosine triphosphate) reduces the extent of biofilm assembly roughly 40% below the control experiments. The physiological effects of adenosine triphosphate are clealy important to biofilm assembly.
Adenosine triphosphate also enhances biofilm assembly for three other bacterial species. The biofilm enhancement effects therefore seem to be general for many bacteria.
The scientists' results go well beyond adherence to artificial surfaces; adenosine triphosphate also enhances Acinetobacter baumannii adherence to lung epithelial cells, by a factor of 100. This microbe is an opportunistic pathogen that is resistant to multiple antibiotics and is a leading cause of serious infections acquired at the hospital.
Similar results were obtained when the lung cells were physically damaged. It's reasonable to conclude that the adenosine triphosphase danger signal greatly facilitates bacterial biofilm assembly in medically-relevant settings.
Implications.
Human cells and pathogenic bacteria respond to the same biochemical danger signal (release of the enzyme adenosine triphosphase), in a biochemical race to stay one step ahead of the other. How can this discovery be used to combat bacterial biofilms?
Perhaps medical efforts aimed at preventing bacterial biofilm assembly can be directed towards either inhibiting adenosine triphosphase release, or removing excessive extracellular levels of the enzyme from the body. Such removal may hinder rapid response to bacterial invasion by the immune system, but if it prevents pathogens from creating an essentially unassailable foothold in the body, the tradeoff may be beneficial.
NOTE: The scientists' research was funded by the University of Michigan.
Xi, C., & Wu, J. (2010). dATP/ATP, a Multifunctional Nucleotide, Stimulates Bacterial Cell Lysis, Extracellular DNA Release and Biofilm Development PLoS ONE, 5 (10) DOI: 10.1371/journal.pone.0013355