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Beaufay, F.

Publications and source records attributed to Beaufay, F..

2 recordsLinked to original sources

Bacterial persistence emerges mainly from antibiotic-specific networks rather than slow growth

Bacterial persisters are rare phenotypic variants that survive antibiotic treatment and contribute to infection relapse and resistance emergence, yet the genetic basis of persistence remains only partially understood. Here, we developed a genome-wide Tn-seq approach to identify genes and pathways involved in persistence in exponentially growing Escherichia coli while avoiding persister enrichment and controlling for the confounding effects of growth. We found that persistence was largely independent of growth, and mutations that impaired growth could either increase or decrease survival. Furthermore, persistence was strongly antibiotic-specific. Ampicillin persistence relied primarily on pathways linked to energy metabolism, whereas ofloxacin persistence was associated on pathways involved in DNA repair and the maintenance of genome integrity. This study supports a model in which bacterial persistence is mainly an antibiotic-specific phenomenon governed by distinct physiological pathways rather than being universally associated with growth arrest.

microbiology↗

Polyphosphate Functions In Vivo as Iron Chelator and Fenton Inhibitor

Maintaining cellular iron homeostasis is critical for organismal survival. Whereas iron depletion negatively affects the many metabolic pathways that depend on the activity of iron-containing enzymes, any excess of iron can cause the rapid formation of highly toxic reactive oxygen species (ROS) through Fenton chemistry. Although several cellular iron chelators have been identified, little is known about if and how organisms can prevent the Fenton reaction. By studying the effects of cisplatin, a commonly used anticancer drug and effective antimicrobial, we discovered that cisplatin elicits severe iron stress and oxidative DNA damage in bacteria. We found that both of these effects are successfully prevented by polyphosphate (polyP), an abundant polymer consisting solely of covalently linked inorganic phosphates. Subsequent in vitro and in vivo studies revealed that polyP provides a crucial iron reservoir under non-stress conditions, and effectively complexes free iron and blocks ROS formation during iron stress. These results demonstrate that polyP, a universally conserved biomolecule, plays a hitherto unrecognized role as an iron chelator and an inhibitor of the Fenton reaction.

microbiology↗