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article imageNew cellular target to weaken drug-tolerant bacteria

By Tim Sandle     Sep 15, 2018 in Science
Canadian microbiologists have located a new cellular target that can weaken the bacterium Pseudomonas aeruginosa. This organism, which has a multi-drug resistant form, presents a severe threat to patients with cystic fibrosis.
The research focuses on a different approach to tackling antimicrobial-tolerant bacteria. Such organisms present a major threat to healthcare settings. In a a few cases microorganisms are naturally resistant to particular antimicrobial agents. It is more common however when microorganisms that were once susceptible to the action of particular antimicrobial agents develop resistance; this can occur, for example, by 'gene swapping'. These organisms pose a particular risk to the young, the elderly and to those with weak or suppressed immune systems.
Since there remains a considerable knowledge gap in relation to the mechanisms that enable some organisms to develop tolerance to certain antimicrobials, the research represents a significant step in terms of tackling multi-drug resistant organisms. Considerable research is taking place in academia to address the problem, although research from pharmaceutical companies has largely stalled due to the low return on investment that can be realized from producing new types of antimicrobials.
With the new development, the microbiologists have identified a new cellular target that can weaken the bacterium Pseudomonas aeruginosa. Ps. aeruginosa is a common Gram-negative, rod-shaped bacterium that can cause disease in plants and animals. The organism has an association with water systems. In terms of health-settings, the bacterium poses a significant risk to those with cystic fibrosis. This is because the organism develop into a biofilms in the lungs of people with cystic fibrosis, and this can prove fatal.
Commenting on the new target, researcher Dr. Dao Nguyen. from the McGill University Health Centre, said: "We identified a new function important to antibiotic tolerance, which could be targeted to enhance the activity of our current antibiotics. This is critical if we want to improve the efficacy of our antibiotics and prevent such treatments from failing."
The breakthrough relates to a phase when Ps. aeruginosa is under stress (such as a point when it lacks nutrients). Under these conditions, the organism deploys a stress signaling system and defense enzyme (called superoxide dismutase) in order to modify its cell membrane. This results in the organism becoming less permeable to molecules which prevents antibiotics from penetrating the cell. By inhibiting this enzyme activity, or interfering with the stress signaling system, the microbiologists found they could make the bacterium more susceptible to antibiotics. Further research will focus on streamlining this mechanism.
The research has been published in the journal Proceedings of the National Academy of Sciences, with the research paper titled "Superoxide dismutase activity confers (p)ppGpp-mediated antibiotic tolerance to stationary-phase Pseudomonas aeruginosa."
More about Bacteria, Microbiology, Pseudomonas aeruginosa, Cystic fibrosis
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