Healthcare settings are ideal for infections from antibiotic resistant microbes, with immune compromised patients and selection pressure applied by use of multiple antimicrobials. P. aeruginosa is a common cause of potentially fatal chronic infections such as sepsis and pneumonia due to its ability to form biofilms with its neighbours. The EU-funded project SYSBIOFILM (Systems biology of Pseudomonas aeruginosa in biofilms) has taken a systems approach at the genetic level to identify candidate drug targets. Researchers imitated specific microenvironments containing microbial communities protected with biofilms. Metabolic reconstructions of the bacterium showed the effects of various gene deletions on growth within various biofilm environments and identified 26 essential genes. None of these genes were essential in only one of the conditions but the researchers found 17 combinations of 21 different genes that were conditionally essential. Oxygen limited conditions were effective in slowing microbial growth and eight gene pairs showed particular promise as drug targets. In another important strand to the research on P. aeruginosa, SYSBIOFILM investigated the potential impact of gut-inhabiting bacteria on overall human metabolism. P. aeruginosa inhabits the human gut at low levels in healthy individuals. The integrated model of the human gut inhabitant Bacteroides thetaiotaomicron and the mouse metabolic reconstruction allowed metabolite exchange. Varying dietary regimes in terms of fat, protein and carbohydrate composition provided examples of both competition and symbiosis through mutually beneficial cross-feeding. A first, this analysis represents a comprehensive description of the co-metabolism between a host and its commensal microbe. The work of the SYSBIOFILM project has tackled two of the most important themes and challenges of contemporary biology. Antimicrobial resistance and the holistic effects of gut bacteria on humans have wide-ranging applications in healthcare and life sciences. Results have been published in two high-profile peer-reviewed journals, PLoS One and Gut Microbes.
Systems biology, gut bacteria, antibiotic resistant microbes, biofilm, symbiosis