Bacterial metabolism and antibiotic resistance

With the rise of antibiotics resistance, medicinal chemistry is confronted to the declining arsenal to fight bacterial infections. P. aeruginosa is a model organism of chronic infections requiring prolonged therapy complicated by emergence of resistance. Prior work has highlighted how aminoglycoside susceptibility varies with environment.

We study the impact of various carbon sources on central metabolism and identify antagonistic behaviors linked to acceleration of central metabolism or diversion of energy sources into anapleurotic reactions. These changes in central metabolism greatly impact the effect of aminoglycoside. Surprisingly, at equal carbon concentration, protective carbon sources display a dominant negative effect on potentiating carbon sources, consistent with the diversion of carbon flux. Importantly, the protective effect seen here may play a role in infection as it is present in experimental biofilms and the pathway producing such protective carbon sources are overexpressed in diseases such as P. aeruginosa infection in cystic fibrosis patients. Understanding such roles can lead to novel therapeutic strategies.