## 8 Membrane and Cell-Wall Modifications in Response to PPCs  
### Cell-Wall Modifications  
_Lactobacillus_ regulates the expression of genes and proteins involved in the biosynthesis of all types of macromolecular components of the cell envelope in response to PPCs, including peptidoglycan (PG), teichoic acids (TAs), and capsular polysaccharides (cps). Modification of the biosynthesis of PG precursors is a known adaptation to stress conditions in Gram-positive bacteria [62, 63]. Some PPCs such as tannic acid inflict injuries in the cell wall leading to rougher cell surfaces and leakages [64]. To circumvent the inhibitory effects of tannic acid, _L. plantarum_ modifies its profile of PBPs (penicillin-binding proteins) (64), which are enzymes known to play a key role in PG biosynthesis. In addition, _L. plantarum_ respond to TA aggression by overproducing LdhD (D-lactate dehydrogenase) and DapF (diaminopimellate (DAP) epimerase), two proteins required for the biogenesis of the PG precursors D-lactate and _meso_-diaminopimelic acid (meso-DAP), respectively [37]. Similarly, _L. hilgardii_ and _L. acidophilus_ NCFM overexpressed LdhD under tannic acid [44] or rutin stress [45], respectively. In addition to LdhD, _L. acidophilus_ NCFM overexpressed GlmU in the presence of rutin, this enzyme catalyzing the last steps of UDP-GlcNAc, one of the cell-wall peptidoglycan precursors. \(p\)-CA injures and leads the bacterial membrane to become leaky [65]. The transcriptomic response of _L. plantarum_ to \(p\)-CA [25] revealed overexpression of _aad_ (D-alanyl-d-alanine dipeptidase) and _hicD2_ (D-hydroxysiocaproate dehydrogenase), which reportedly modify the biosynthesis of PG precursors [66]. This profile coincided with a marked decrease in the expression of genes encoding putative lytic glycosyl-transferases (_lp_0302, _lp_3014, _lp_3015_) and a muroeptidase (_lp_3421_), all encompassed within the peptidoglycanhydrolase (PGH) complement of _L. plantarum_ WCFS1 [67]. This transcriptome reprogramming does point to PG modification, reduction in PG turnover, and repression of cell lysis to counter the effects of _p_-CA [25]. The production levels and structure of wall teichoic acids (WTA) and lipoteichoic acids (LTA) from _L. plantarum_ were likely affected by the presence of some PPCs as judged by the altered expression of genes and proteins responsible for their production. TagE6 (poly(glycerol-phosphate) \(\alpha\)-glycostransferase), an enzyme involved in glucosyl substitution of poly(ribitol-5-P) WTA [68], was induced after exposure to tannic acid [37] and transcriptionally overexpressed in response to OLE [28] or HXT [29]. Induction of genes of the _tarl_[_]_KL locus is a genetic marker of WTA backbone alidid switching in _L. plantarum_[68] as it is responsible for poly(ribitol-5-P) WTA production, an alternative WTA variant to the wild-type glycerol-containing backbone. The _tarl_[_]_K and the _tar_K genes are transcriptionally induced in response to OLE [28] and HXT [29], respectively, suggesting that WTA backbone alididid switching occurs in response to these PPCs. Downregulation of _tagD2_ (_lp_1248_), which CDP-activates glycerol-P, was also observed in presence of HXT, further supporting WTA backbone alidid switching. In addition, downregulation of _gta1_ which encodes an LTA glycosylation protein suggests changes in the decoration of LTAs exposed to HXT. The capsular polysaccharide (_cps_) genes encode the enzymatic machinery involved in the different steps of the repeating unit synthesis, export, and polymerization of these macromolecules in lactic acid bacteria [69; 70]. The decreased expression of _cps_ genes was a common transcriptome response of _L. plantarum_ WCFS1 to _p_-CA [25], RSV [27], and OLE [28]. These genes are organized in four _cps_ gene clusters distributed along the genome of this microorganism. In the presence of _p_-CA, up to 16 out of all 36 _cps_ genes that were encompassed within _cps1_, _cps3_, and _cps4_ gene clusters were downregulated.