| Summary: | <p>Abstract</p> <p>Background</p> <p>The food-borne pathogen <it>Listeria monocytogenes</it> 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 <it>L</it>. <it>monocytogenes</it> are susceptible to these antibiotics, their action is only bacteriostatic and consequently, this bacterium is regarded as tolerant to β-lactams. In addition, <it>L</it>. <it>monocytogenes</it> 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 <it>L</it>. <it>monocytogenes</it> to β-lactams.</p> <p>Results</p> <p>The <it>hly</it>-based promoter trap system was applied to identify penicillin G-inducible genes of <it>L</it>. <it>monocytogenes</it>. 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 (<it>fri</it>), a two-component phosphate-response regulator (<it>phoP</it>) and an AraC/XylS family transcriptional regulator (<it>axyR</it>), to the susceptibility and tolerance of <it>L</it>. <it>monocytogenes</it> 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<it>fri</it> 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 <it>L</it>. <it>monocytogenes</it> to cefalotin and cephradine.</p> <p>Conclusions</p> <p>The present study has identified Fri as an important mediator of β-lactam tolerance and innate resistance to cephalosporins in <it>L</it>. <it>monocytogenes</it>. PhoP and AxyR are probably involved in transmitting signals to adjust the rate of growth of <it>L</it>. <it>monocytogenes</it> under β-lactam pressure, but these regulators do not play a significant role in susceptibility and tolerance to this class of antibiotics.</p>
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