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[email protected]The promise of microbial engineering for developing new strategies for tackling human disease
“...the synthetic manipulation of bacteria and viruses allows the design of new strategies that offer both hope and new opportunities in the fight against human diseases.”
Ignacio López-Goñi
Department of Microbiology & Parasitology, Institute of Tropical Health, University of Navarra, 31008, Pamplona, Spain
Tel.: +34 948
[email protected]In May 2010 a team lead by J Craig Venter reported the creation of a bacterial chromosome and its transfer into a bacterium where it suc- cessfully replicated [1]. This work demonstrated the design, synthesis and assembly of a synthetic genome of Mycoplasma mycoides and its subse- quent transfer into Mycoplasma capricolumas, a receptor cell, to create a new strain of M. mycoides that was controlled by a synthetic chromosome. The bacterium was able to self-replicate and syn- thesize new proteins. It took 15 years for this work to be completed, during which time new tools, techniques and concepts from synthetic biology were developed. This demonstrates the enormous possibilities for the future offered by microbial engineering, the discipline combining microbiol- ogy, molecular biology and chemical engineering; that is, the manipulation of microorganisms for the development of new products and applications for use in humans.
“This demonstrates the enormous possibilities for the future offered by microbial engineering, the discipline combining microbiology, molecular biology and chemical engineering...”
In recent months, two studies have been pub- lished that, owing to their originality and under- lying strategy, are two new pieces of evidence showing the future possibilities of manipulating microorganisms, in both cases to combat human diseases. In one study, bacteria have been manipu- lated to fight against infectious disease, and in the other, viruses have been modified as a tool to combat cancer.
One of the studies, published in Molecular Systems Biology [2], is based on synthetic biol- ogy techniques by which a microbe is manip- ulated so that it performs functions that it is normally unable to carry out, as is the case of killing another bacterium, to prevent or treat Pseudomonas aeruginosa infections in humans. The lack of progress in the development of new antibiotics, together with the increase in the emergence of multiresistant pathogens make the development of new antimicrobial strate- gies a priority. Saeidi et al. [2] have designed a novel microbial engineering system that allows P. aeruginosa, a Gram-negative bacterium capable of colonizing the respiratory and gas- trointestinal systems in humans, to be detected and killed. P. aeruginosa is the cause of approxi- mately 10% of all nosocomial infections and is especially serious in immunocompromised patients. Normally, such infections are treated with antibiotics, but P. aeruginosa is intrinsi- cally resistant to many antibiotics and anti- microbials, in part owing to the efficacy of its efflux-type systems. In this study, the authors describe the design and construction of a genetic system using, as a vehicle, a nonpathogenic strain of Escherichia coli capable of detecting the P. aeruginosa pathogen, exploding and then releasing antimicrobial substances which kill Pseudomonas – a system reminiscent of a real bacterial ‘kamikaze’.
This new design, called the pathogen sensing and killing system, functions in various stages. First, the bacterial ‘kamikaze’ (E. coli) detects the molecules of acyl homoserine lactone produced by the quorum sensing system of Pseudomonas; then in E. coli the production of