## 3 Oxidative Stress Responses Modulated by PPCs  
Since antimicrobials usually feature the overproduction of reactive oxygen species (ROS) to exert their activity [3], oxidative stress responses can be expected when microbes interact with PPCs. Accordingly, _Lactobacillus_ exposed to PPCs differentially expressed genes and proteins required to cope with oxidative stress (Table 1). Methionine sulfoxide reductase, glutathione reductase, components of the thioredoxin (Trx)-thioreductase (TrxR) system, and a broad set of genes dedicated to methionine (Met) biosynthesis were transcriptionally upregulated in _L. plantarum_ in response to \(p\)-CA [25]. This response is required to counter thiol-specific oxidative stress, and it is consistent with the pro-oxidative stress arising from \(p\)-CA autoxidation [31]. Methionine residues in proteins can be exploited by bacteria as ROS scavengers to protect proteins and lipids from oxidation [32; 33]. Genes responsive to thiol-specific oxidative stress are induced by HXT in _L. plantarum_ WCFS1, including methionine sulfoxide reductase, glutathione reductase, and a regulator of disulfide bond formation [29]. The stilbene RSV absolutely requires copper, a redox-active metal, to generate RSV-derived ROS. To counter this potential pro-oxidant behavior, _L. plantarum_ responds to RSV  
Figure 1: Venn diagram assembled from _Lactiplantiobacillus plantarum_ WCFS1 genes differentially expressed in response to various plant phenolic compounds: \(p\)-coumarin acid (\(p\)-CA), resveratrol (RSV), hydroxytyrosol (HXT), and oleupopei (OLE). by inducing a multicopper oxidase and CopR [27], a transcription factor that senses the copper status of the cytoplasm and controls the expression of copper export ATPases [34]. In agreement with this role, CopR has been suggested to play an important role in elevating resistance to H\({}_{2}\)O\({}_{2}\) stress in \(L\). _plantarum_[35]. In addition, RSV induces two zinc ABC transporters, a metal that competes with and antagonizes copper. One of these \(L\). _plantarum_ transporters (_lp_0464_) was also induced by OLE [28], and the corresponding \(L\). _brevis_ homologous permease (_lvis_047_) was induced in cells exposed to ferulic acid [23] (Table 1). _L. plantarum_ downregulates a Fe\({}^{2+}\) transporter _mntH3_[36] upon HXT stress [29], which would diminish hydroxyl radical production arising from the Fenton reaction of this metal with H\({}_{2}\)O\({}_{2}\). According to these profiles, management of the transport of transition metals participating in the Fenton-like chemistry seems a strategy used by _Lactobacillus_ spp. to prevent an increase of the oxidative stress generated by PPCs. Enzymes inactivating toxic oxygen radicals, which are part of the first defense against oxygen damage, were also implicated in the response to some PPCs (Table 1). The gene coding for the NADH peroxidase (_npr2_) was overexpressed by \(L\). _plantarum_ in the presence of OLE [28] or HXT [29]. A proteomic study revealed that the NPR2 enzyme was also upregulated in the presence of tannic acid [37]. Catalase (_kat_), which also detoxifies H\({}_{2}\)O\({}_{2}\), was induced in \(L\). _plantarum_ upon HXT stress [29]. In addition, pyruvate oxidase (_pox_), an enzyme linked to oxidative stress resistance, was transcriptionally induced by OLE [28] or HXT [29]. The differential expression of the _cysE-metC-cysK_ operon constituted a common response, except for GA, to PPCs in \(L\). _plantarum_ (Table 1). In _Lactococcus lactis_ (a close relative of \(L\). _plantarum_), the _metC-cysK_ operon is well correlated with robustness toward oxidative stress [38]. In \(L\). _plantarum_, the _cysE-metC-cysK_ operon was downregulated upon \(p\)-CA [25] or RSV stress [27] but upregulated in the presence of OLE [28] or HXT [29]. The _metC_ and _cysK_ genes encode cystathionine-\(\gamma\)-lysae (CSE) and cystathionine-\(\beta\)-syntase (CBS), respectively, which are the microbial orthologs of the mammalian CSE and CBS.