JMM Editor's Choice: drivers of persistent Pseudomonas infection in cystic fibrosis

Posted on March 18, 2019   by Microbiology Society

The Journal of Medical Microbiology (JMM) is a journal published by the Microbiology Society, focused on providing a comprehensive coverage of medical, dental and veterinary microbiology and infectious diseases, including bacteriology, virology, mycology and parasitology. This month, Professor Vincent Cattoir has selected an outstanding paper from the March issue to highlight as Editor’s Choice. The paper, titled 'Agmatine accumulation by Pseudomonas aeruginosa clinical isolates confers antibiotic tolerance and dampens host inflammation' discusses the role of agmatine, a molecule produced by P. aeruginosa, on antibiotic resistance and the host immune response.

This interesting study demonstrates that agmatine, a pre-polyamine intermediate metabolite, is involved in the long-term persistence of Pseudomonas aeruginosa in patients suffering from cystic fibrosis. The authors showed experimentally that accumulation of agmatine is due to mutations in aguA and that agmatine-hyperproducing P. aeruginosa isolates exhibit an increased tolerance to cationic antibiotics. Their research also found that agmatine decreases IL-8 production by airway epithelial cells and agmatine hyperproduction impairs neutrophil recruitment into the airways in an acute pneumonia model.

 

Agmatine accumulation by Pseudomonas aeruginosa clinical isolates confers antibiotic tolerance and dampens host inflammation

Chronic lung infection by Pseudomonas aeruginosa is a primary cause of mortality among people living with cystic fibrosis. Treatment is made even more complicated by the adaptation of this bacterium to the host over time, including ‘loss-of-function’ mutations that give the bacterium significant advantages such as resistance to antibiotics. We identified a loss-of-function mutation among clinical isolates of P. aeruginosa that resulted in the overproduction of the metabolite agmatine. Agmatine accumulation in the growth medium resulted in resistance to multiple classes of antibiotics and manipulation of the host immune response, which may have important consequences for the chronic growth of Pseudomonas in the cystic fibrosis lung.

Ryan Hunter