The Staphylococcus aureus Protein-Coding Gene gdpS Modulates sarS Expression via mRNA-mRNA Interaction

Abstract

bStaphylococcus aureus is an important Gram-positive pathogen responsible for numerous diseases ranging from localized skin infections to life-threatening systemic infections. The virulence of S. aureus is essentially determined by a wide spectrum of factors, including cell wall-associated proteins and secreted toxins that are precisely controlled in response to environmental changes. GGDEF domain protein from Staphylococcus (GdpS) is the only conserved staphylococcal GGDEF domain protein that is involved not in c-di-GMP synthesis but in the virulence regulation of S. aureus NCTC8325. Our previous study showed that the inactivation of gdpS generates an extensive change of virulence factors together with, in particular, a major Spa (protein A) surface protein. As reported, sarS is a direct positive regulator of spa. The decreased transcript levels of sarS in the gdpS mutant compared with the parental NCTC8325 strain suggest that gdpS affects spa through interaction with sarS. In this study, site mutation and complementary experiments showed that the translation product of gdpS was not involved in the regulation of transcript levels of sarS. We found that gdpS functioned through direct RNA-RNA base pairing with the 5= untranslated region (5=UTR) of sarS mRNA and that a putative 18-nucleotide region played a significant role in the regulatory process. Furthermore, the mRNA half-life analysis of sarS in the gdpS mutant showed that gdpS positively regulates the mRNA levels of sarS by contributing to the stabilization of sarS mRNA, suggesting that gdpS mRNA may regulate spa expression in an RNA-dependent pathway.

RNase III-CLASH of multi-drug resistant Staphylococcus aureus reveals a regulatory mRNA 3′UTR required for intermediate vancomycin resistance

“…To our knowledge, vigR is the fourth example of a bacterial mRNA that has trans -acting regulatory functions. In S. aureus , the CDS region of gdpS was shown to directly interact and stabilise the 5′UTR of sarS , however, the mechanism was not determined 49 . In the gram-positive pathogen, Listeria monocytogenes , interactions between the 3′UTR of hly and the 5′UTR of prsA block exonucleolytic digestion of prsA mRNA by RNase J1 50 .…”

Glutamine synthetase mRNA releases sRNA from its 3’UTR to regulate carbon/nitrogen metabolic balance

“…The two events on dual-function sRNAs are mutually exclusive depending on translation efficiency, RNA stability, and temperature (Aoyama et al , 2021; Raina et al , 2022; Balasubramanian & Vanderpool, 2013; Aoyama et al , 2022). Moreover, post-transcriptional regulation via mRNA-mRNA interactions is not rare in Gram-positive bacteria (Liu et al , 2015; Chen et al , 2015; Ignatov et al , 2020; Mediati et al , 2022).…”

Regulation of Staphylococcus aureus Virulence

“…On the post-transcriptional level, SarH1 is regulated by GdpS. The mRNA product of the gdpS gene directly interacts with the 5`UTR of sarH1 , resulting in a more stable sarH1 mRNA (153). SarH1 itself acts as a repressor of hla , and it also acts as a positive regulator of spa , which is located directly downstream the sarH1 locus (151).…”