In Pseudomonas aeruginosa (P. aeruginosa), transcription factors (TFs) are important mediators in the genetic regulation of adaptability and pathogenicity to respond to multiple environmental stresses and host defences. The P. aeruginosa genome harbours 371 putative TFs; of these, about 70 have been shown to regulate virulence-associated phenotypes by binding to the promoters of their target genes. Over the past three decades, several techniques have been applied to identify TF binding sites on the P. aeruginosa genome, and an atlas of TF binding patterns has been mapped. The virulence-associated regulons of TFs show complex crosstalk in P. aeruginosa’s regulatory network. In this review, we summarise the recent literature on TF regulatory networks involved in the quorum-sensing system, biofilm formation, pyocyanin synthesis, motility, the type Ⅲ secretion system, the type Ⅵ secretion system, and oxidative stress responses. We discuss future perspectives that could provide insights and targets for preventing clinical infections caused by P. aeruginosa based on the global regulatory network of transcriptional regulators.

The latent infection by herpes virus type 1 (HSV-1) may be lifelong in trigeminal ganglia and a suspected cause of Alzheimer's Disease (AD) and Amyotrophic lateral sclerosis (ALS). Whether and how N6-methyladenosine (m6A) modification of viral RNAs affects virus infection are poorly understood. Here, we report that HSV-1 infection enhanced the expression of m6A writers (METTL3, METTL14) and readers (YTHDF1/2/3) at the early infection stage and decreased their expression later on, while suppressed the erasers' (FTO, ALBKH5) expression immediately upon infection to facilitate viral replication. Inhibiting m6A modification by 3-deazaadenosine (DAA) significantly decreased viral replication and reduced viral reproduction over 1000 folds. More interestingly, depleting the writers and readers by siRNAs inhibited virus replication and reproduction; whereas depleting the erasers promoted viral replication and reproduction. Silencing YTHDF3 strikingly decreased viral replication by up to 90%, leading to reduction of up to 10-fold viral replication and over 100-fold virus reproduction, respectively. Depletion of m6A initiator METTL3 (by 60%–70%) by siRNA correlatedly decreased viral replication 60%–70%, and reduced virus yield over 30-fold. Consistently, ectopic expression of METTL3 largely increased virus yield. METTL3 knockdown suppressed the HSV-1 intermediate early and early genes (ICP0, ICP8 and UL23) and late genes (VP16, UL44, UL49 and ICP47); while ectopic expression of METTL3 upregulated these gene expression. Results from our study shed the lights on the importance for m6A modification to initiate HSV-1 early replication. The components of m6A modification machinery, particularly m6A initiator METTL3 and reader YTHDF3, would be potential important targets for combating HSV-1 infections.