Base Pairing Interaction between 5′- and 3′-UTRs Controls icaR mRNA Translation in Staphylococcus aureus

Mozos, Igor Ruiz de los; Vergara-Irigaray, Marta; Segura, Víctor; Villanueva, Maite; Bitarte, Nerea; Saramago, Margarida; Domingues, Susana; Arraiano, Cecília M.; Fechter, Pierre; Romby, Pascale; Valle, Jaione; Solano, Cristina; Lasa, Íñigo; Toledo‐Arana, Alejandro

doi:10.1371/journal.pgen.1004001

Cited by 90 publications

(123 citation statements)

References 79 publications

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“…The two transcription ends could be due to transcription being terminated at two terminators or to processing of the longer transcript. However, a strong intrinsic terminator has been identified 36 bp downstream of the rbsR gene (41). Based on the start site and the predicted terminator, we estimated the rbsR transcript to be ϳ1.1 kb, which matches the size of the shorter transcript that we identified by Northern blotting.…”

Section: Identification Of Pcap-binding Proteinssupporting

confidence: 56%

“…The consensus RbsR binding site in the promoter region of the rbs operon in the Bacillus/Clostridium group of bacteria, including S. aureus, has been defined by a comparative approach (41). The predicted consensus RbsR box upstream of the rbsUDK operon in S. aureus bears no resemblance to the RbsR binding site in the cap promoter region as defined by footprinting in that study.…”

Section: Discussionmentioning

confidence: 90%

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RbsR Activates Capsule but Represses the rbsUDK Operon in Staphylococcus aureus

Lei

Lee

2015

J Bacteriol

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Staphylococcus aureus capsule is an important virulence factor that is regulated by a large number of regulators. Capsule genes are expressed from a major promoter upstream of the cap operon. A 10-bp inverted repeat (IR) located 13 bp upstream of the ؊35 region of the promoter was previously shown to affect capsule gene transcription. However, little is known about transcriptional activation of the cap promoter. To search for potential proteins which directly interact with the cap promoter region (Pcap), we directly analyzed the proteins interacting with the Pcap DNA fragment from shifted gel bands identified by electrophoretic mobility shift assay. One of these regulators, RbsR, was further characterized and found to positively regulate cap gene expression by specifically binding to the cap promoter region. Footprinting analyses showed that RbsR protected a DNA region encompassing the 10-bp IR. Our results further showed that rbsR was directly controlled by SigB and that RbsR was a repressor of the rbsUDK operon, involved in ribose uptake and phosphorylation. The repression of rbsUDK by RbsR could be derepressed by D-ribose. However, D-ribose did not affect RbsR activation of capsule. IMPORTANCEStaphylococcus aureus is an important human pathogen which produces a large number of virulence factors. We have been using capsule as a model virulence factor to study virulence regulation. Although many capsule regulators have been identified, the mechanism of regulation of most of these regulators is unknown. We show here that RbsR activates capsule by direct promoter binding and that SigB is required for the expression of rbsR. These results define a new pathway wherein SigB activates capsule through RbsR. Our results further demonstrate that RbsR inhibits the rbs operon involved in ribose utilization, thereby providing an example of coregulation of metabolism and virulence in S. aureus. Thus, this study further advances our understanding of staphylococcal virulence regulation. Staphylococcus aureus produces a large number of virulence factors that endow the organism with the ability to cause a wide range of diseases in humans and animals. The expression of virulence genes is controlled by an equally impressive number of regulators forming a complex regulatory network (1-3). Although the regulation of virulence genes has been the subject of extensive studies recently, our knowledge of the virulence regulatory network in S. aureus is still fragmented. To further understand virulence regulation, we have been studying the S. aureus virulence regulatory network by employing capsule as a model virulence factor (4-7). Capsule is an antiphagocytic virulence factor, and the majority of S. aureus strains produce either type 5 or type 8 capsule (8, 9). Sixteen cap genes, which are organized as a long operon, are required for the biosynthesis of either type of capsule (10). The genetic loci for the type 5 and type 8 capsules (cap5 and cap8) are allelic, with the four genes in the middle of the operon being type specific...

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Section: Identification Of Pcap-binding Proteinssupporting

confidence: 56%

Section: Discussionmentioning

confidence: 90%

RbsR Activates Capsule but Represses the rbsUDK Operon in Staphylococcus aureus

Lei

Lee

2015

J Bacteriol

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“…A s A promoter consensus was found centered 10 nts upstream the C1 start of the transcript originating at nt ¡3242. This longer transcript correlates with recent transcriptomic data, 38 corroborating our findings that LytM is expressed as part of a large operon including SA0264 (SA0264-lytM). Additionally, we identified a transcript starting at C-356 with regard to the lytM AUG. We suggest that the transcripts with 5 0 ends at C-411 and C-356, that were identified by primer extension and RACE, respectively, correspond to processed transcripts from the longer SA0264-lytM transcript (Fig.…”

supporting

confidence: 91%

“…Intriguingly, we have observed that lytM is also produced from a bicistronic operon, which includes the upstream SA0264 gene encoding for a protein similar to penicillin amidase. The same transcriptional start site was also observed in S. aureus 15981 strain 38 indicating that the presence of a weakly expressed bicistronic operon encompassing SA0264 and lytM is conserved in S. aureus strains. We observed this longer lytM transcript at both the exponential and stationary growth phases and found that the steady state yield does not depend on RNAIII levels (Fig.…”

Section: Discussionmentioning

confidence: 52%

Various checkpoints prevent the synthesis ofStaphylococcus aureuspeptidoglycan hydrolase LytM in the stationary growth phase

et al. 2016

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In Staphylococcus aureus, peptidoglycan metabolism plays a role in the host inflammatory response and pathogenesis. Transcription of the peptidoglycan hydrolases is activated by the essential 2-component system WalKR at low cell density. During stationary growth phase, WalKR is not active and transcription of the peptidoglycan hydrolase genes is repressed. In this work, we studied regulation of expression of the glycylglycine endopeptidase LytM. We show that, in addition to the transcriptional regulation mediated by WalKR, the synthesis of LytM is negatively controlled by a unique mechanism at the stationary growth phase. We have identified 2 different mRNAs encoding lytM, which vary in the length of their 5 0 untranslated (5 0 UTR) regions. LytM is predominantly produced from the WalKR-regulated mRNA transcript carrying a short 5 0 UTR. The lytM mRNA is also transcribed as part of a polycistronic operon with the upstream SA0264 gene and is constitutively expressed. Although SA0264 protein can be synthesized from the longer operon transcript, lytM cannot be translated because its ribosome-binding site is sequestered into a translationally inactive secondary structure. In addition, the effector of the agr system, RNAIII, can inhibit translation of lytM present on the operon without altering the transcript level but does not have an effect on the translation of the upstream gene. We propose that this dual regulation of lytM expression, at the transcriptional and post-transcriptional levels, contributes to prevent cell wall damage during the stationary phase of growth.

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“…Indeed, mRNA structures at 5 0 regions strongly impact translation initiation and are therefore target of several mechanisms of regulations. Besides, recent observations also revealed that bacterial mRNAs carry large 3 0 UTRs, which impact the translation efficiency [31].…”

Section: Impact Of the Transcriptionetranslationedegradation Couplingmentioning

confidence: 99%

Multiple ways to regulate translation initiation in bacteria: Mechanisms, regulatory circuits, dynamics

et al. 2015

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Base Pairing Interaction between 5′- and 3′-UTRs Controls icaR mRNA Translation in Staphylococcus aureus

Cited by 90 publications

References 79 publications

RbsR Activates Capsule but Represses the rbsUDK Operon in Staphylococcus aureus

RbsR Activates Capsule but Represses the rbsUDK Operon in Staphylococcus aureus

Various checkpoints prevent the synthesis ofStaphylococcus aureuspeptidoglycan hydrolase LytM in the stationary growth phase

Multiple ways to regulate translation initiation in bacteria: Mechanisms, regulatory circuits, dynamics

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