Against LC-derived inhibitors principally by controlling gene transcription, likely reflecting evolution
Against LC-derived inhibitors principally by controlling gene transcription, possibly reflecting evolution of certain bacterial responses to LC-derived inhibitors. Even though enteric bacteria usually do not ordinarily encounter industrial lignocellulosic hydrolysates, they most likely encounter exactly the same suite of compounds from digested plant material within the mammalian gut. As a result, evolution of certain responses is affordable. A important question for future research is irrespective of whether phenolic amides, not ordinarily present in digested biomass, will also invoke these responses within the absence of carboxylates or aldehydes. We note that the apparent absence of a translational regulatory response in the cellular defense against LC-derived inhibitors doesn’t preclude involvement of either direct or indirect post-transcriptional regulation in fine-tuning the response. Our proteomic measurements would likely not have detected fine-tuning. In addition, we did detect an apparently indirect induction by inhibitors of protein degradation in stationary phase, possibly in response to C starvation (Figure 6C). Ultimately, we note that the sRNA micF, a recognized post-transcriptional regulator, is actually a constituent in the MarASoxSRob regulon and was upregulated by inhibitors. Despite the fact that self-confidence was insignificant due to poor detection of sRNAs in RNAseq information, the induction of micF was confirmed within a separate study of sRNAs (Ong and Landick, in preparation). Thus, a more focused study from the involvement of sRNAs in responses to LC inhibitors would likely be informative. MarASoxSRob can be a complex regulon consisting of the three inter-connected major AraC-class regulators that bind as monomers to 20-bp websites in promoters with hugely overlapping specificity and synergistically regulate 50 genes implicated in resistance to numerous antibiotics and xenobiotics, solvent tolerance, outer membrane permeability, DNA repair, along with other functions (Chubiz et al., 2012; Duval and Lister, 2013; GarciaBernardo and Dunlop, 2013) (Figure 7). Twenty-three genes, like those encoding the AcrAB olC efflux pump, the NfsAB nitroreductases, the micF sRNA, superoxide MCT4 custom synthesis dismutase, some metabolic enzymes (e.g., Zwf, AcnA, and FumC) and incompletely characterized stress proteins are controlled by all 3 regulators, whereas other genes are annotated as becoming controlled by only a subset with the regulators (Duval and Lister, 2013), ecocyc.org; (Keseler et al., 2013). MarA and SoxS lack the Cterminal dimerization domain of AraC; this domain is present on Rob and seems to mediate regulation by aggregation that may be reversed by effectors (Griffith et al., 2009). Inputs capable of inducing these genes, either by way of the MarR and SoxR repressors that manage MarA and SoxS, respectively, or by direct effects on Rob contain phenolic carboxylates, Cu2 , various organic oxidants, dipyridyl, decanoate, bile salts, Fis, and Crp AMPfrontiersin.orgAugust 2014 | Volume 5 | Post 402 |Keating et al.Bacterial regulatory responses to lignocellulosic inhibitorsFIGURE 7 | Main Regulatory responses of E. coli to aromatic inhibitors identified in ACSH. The big E. coli responses to phenolic carboxylates and amides (left) or responses to aldehydes (suitable) are depicted. Green panels, regulators and signaling interactions that mediate the regulatory responses.Pink panels, direct targets on the regulators that BRDT drug consume reductant (NADPH) for detoxification reactions or deplete the proton motive force through continuous antiporter eff.