The ferritin-like protein Dps protects Salmonella enterica serotype Enteritidis from the Fenton-mediated killing mechanism of bactericidal antibiotics.

Dps is a ferritin-like protein with DNA-binding properties that is capable of affording protection during oxidative stress and during times of nutritional deprivation. Here we present evidence that in exponentially growing Salmonella enterica serotype Enteritidis, Dps is vital for protection against the common killing mechanism of bactericidal antibiotics, a mechanism manifested by hydroxyl radical production via the Fenton reaction. A dps deletion mutant ('dps mutant') was hypersensitive to the bactericidal antibiotics streptomycin, nalidixic acid, norfloxacin and rifampicin compared with its parental strain. However, the observed discrepancy in survivability between the dps mutant and the parental strain following exposure to bactericidal antibiotics was fully alleviated when drug-exposed cultures were treated with an iron chelator, confirming that Fenton-mediated oxidative stress was a major factor in the reduced survival rate of the dps mutant. In addition, deletion of the DNA damage-induced repair protein RecA further intensified the killing capacity of bactericidal antibiotics in a Δdps (i.e. dps deletion) background, implying that Dps and RecA may operate in a synergistic manner to protect against the common killing mechanism of bactericidal antibiotics. The relevance of this work is demonstrated by the need for new and increasingly effective bactericidal therapies. Targeting Dps may represent a means to increase the potency of bactericidal antibiotics in S. enterica and other bacterial pathogens alike.