Teg58, a small regulatory RNA, is involved in regulating arginine biosynthesis and biofilm formation in Staphylococcus aureus

Abstract

Staphylococcus aureus adapts to different environments by sensing and responding to diverse environmental cues. The responses are coordinately regulated by regulatory proteins, and small regulatory RNAs at the transcriptional and translational levels. Here, we characterized teg58, a SarA repressed sRNA, using ChIP-Seq and RNA-Seq analysis of a sarA mutant. Phenotypic and genetic analyses indicated that inactivation of teg58 led to reduced biofilm formation in a process that is independent of SarA, agr, PIA, and PSMs. RNA-Seq analysis of teg58 mutant revealed up-regulation of arginine biosynthesis genes (i.e., argGH) as well as the ability of the mutant to grow in a chemical defined medium (CDM) lacking l-arginine. Exogenous l-arginine or endogenous induction of argGH led to decreased biofilm formation in parental strains. Further analysis in vitro and in vivo demonstrated that the specific interaction between teg58 and the argGH occurred at the post-transcriptional level to repress arginine synthesis. Biochemical and genetic analyses of various arginine catabolic pathway genes demonstrated that the catabolic pathway did not play a significant role in reduced biofilm formation in the teg58 mutant. Overall, results suggest that teg58 is a regulatory sRNA that plays an important role in modulating arginine biosynthesis and biofilm formation in S. aureus.

Janus nanoparticles targeting extracellular polymeric substance achieve flexible elimination of drug-resistant biofilms

“…Moreover, the comparison between the Dex-BSe group and control group demonstrated that in addition to amino acids synthesis and metabolism-related pathways, DEGs were also associated with the quorum sensing and purine metabolism (Supplementary Fig. 12a ), which play important roles in S. aureus biofilm dispersion 57 , 60 . On the other hand, DEGs between the Dex group and control group were only associated with the quorum sensing and purine metabolism (Supplementary Fig.…”

“…4f , hierarchical clustering heatmap of biofilm-related DEGs demonstrates that the genes encoding extracellular proteases, such as sspA and sspB , were significantly upregulated in the Dex-BSe group compared with the control and Dex groups, which are involved in biofilm detachment 60 . In addition, the genes involved in arginine biosynthesis and arginine catabolism such as argF , argH , arcC , arcA , and arcD were also substantially upregulated after Dex-BSe treatment, which is supposed to inhibit the formation of biofilm and facilitate biofilm dissociation 57 . RT-PCR assay was further performed to analyze the expression levels of typical genes, verifying the RNA-seq results (Supplementary Fig.…”

Transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin-resistant Staphylococcus aureus

“…Similarly, Liu et al (2022) found that arginine could promote biofilm formation in P. aeruginosa . Moreover, Adhar et al (2022) reported that the small regulatory RNA Teg58 influenced arginine biosynthesis genes (i.e., argGH encoding arginosuccinate synthetase and lyase) to reduce biofilm formation. However, Zhu et al (2007) indicated that the catabolic pathway of arginine did not play a significant role in the inhibition of biofilm formation in S. aureus .…”

Antimicrobial Resistance and Anti-Biofilms

“…teg58 inhibits arginine synthesis; the arginine biosynthesis gene (argGH) is upregulated in teg58 mutants. Biofilm formation is reduced in parental strains after supplementation with exogenous arginine or endogenous argGH [183]. However, teg49 does not affect biofilm formation.…”