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Background  The food-borne pathogen  Listeria monocytogenes  is the causative agent of listeriosis. The β-lactam antibiotics penicillin G and ampicillin are the current drugs of choice for the treatment of listerial infections. While isolates of  L .  monocytogenes  are susceptible to these antibiotics, their action is only bacteriostatic and consequently, this bacterium is regarded as tolerant to β-lactams. In addition,  L .  monocytogenes  has a high level of innate resistance to the cephalosporin family of β-lactams frequently used to treat sepsis of unknown etiology. Given the high mortality rate of listeriosis despite rational antibiotic therapy, it is important to identify genes that play a role in the susceptibility and tolerance of  L .  monocytogenes  to β-lactams.    Results  The  hly -based promoter trap system was applied to identify penicillin G-inducible genes of  L .  monocytogenes . The results of reporter system studies, verified by transcriptional analysis, identified ten penicillin G-inducible genes. The contribution of three of these genes, encoding a ferritin-like protein ( fri ), a two-component phosphate-response regulator ( phoP ) and an AraC/XylS family transcriptional regulator ( axyR ), to the susceptibility and tolerance of  L .  monocytogenes  to β-lactams was examined by analysis of nonpolar deletion mutants. The absence of PhoP or AxyR resulted in more rapid growth of the strains in the presence of sublethal concentration of β-lactams, but had no effect on the MIC values or the ability to survive a lethal dose of these antibiotics. However, the Δ fri  strain showed impaired growth in the presence of sublethal concentrations of penicillin G and ampicillin and a significantly reduced ability to survive lethal concentrations of these β-lactams. A lack of Fri also caused a 2-fold increase in the sensitivity of  L .  monocytogenes  to cefalotin and cephradine.    Conclusions  The present study has identified Fri as an important mediator of β-lactam tolerance and innate resistance to cephalosporins in  L .  monocytogenes . PhoP and AxyR are probably involved in transmitting signals to adjust the rate of growth of  L .  monocytogenes  under β-lactam pressure, but these regulators do not play a significant role in susceptibility and tolerance to this class of antibiotics.

Identification of a ferritin-like protein of Listeria monocytogenes as a mediator of β-lactam tolerance and innate resistance to cephalosporins