Pathogenic bacteria must rapidly adapt to ever‐changing environmental signals resulting in metabolism remodeling. The carbon catabolite repression, mediated by the catabolite control protein A (CcpA), is used to express genes involved in utilization and metabolism of the preferred carbon source. Here, we have identified RsaI as a CcpA‐repressed small non‐coding RNA that is inhibited by high glucose concentrations. When glucose is consumed, RsaI represses translation initiation of mRNAs encoding a permease of glucose uptake and the FN3K enzyme that protects proteins against damage caused by high glucose concentrations. RsaI also binds to the 3′ untranslated region of icaR mRNA encoding the transcriptional repressor of exopolysaccharide production and to sRNAs induced by the uptake of glucose‐6 phosphate or nitric oxide. Furthermore, RsaI expression is accompanied by a decreased transcription of genes involved in carbon catabolism pathway and an activation of genes involved in energy production, fermentation, and nitric oxide detoxification. This multifaceted RNA can be considered as a metabolic signature when glucose becomes scarce and growth is arrested.

Staphylococcus aureus is usually described as an extracellular opportunistic pathogen, infecting a wide range of organs and tissues.However, it also invades and replicates in various phagocytic or nonphagocytic host cells (Hamza & Li, 2014). To be successful as a pathogen, this bacterium needs to adapt to the hostile environment of the host and must acquire imposed nutriments for its survival.Consequently, the staphylococcal genome encodes several transporters for metabolites (sugars, metals, amino acids, etc.), which are

Regulatory RNAs, present in many bacterial genomes and particularly in pathogenic bacteria such as Staphylococcus aureus , control the expression of genes encoding virulence factors or metabolic proteins. They are extremely diverse and include noncoding RNAs (sRNA), antisense RNAs, and some 5′ or 3′ untranslated regions of messenger RNAs that act as sensors for metabolites, tRNAs, or environmental conditions (e.g., temperature, pH). In this review we focus on specific examples of sRNAs of S. aureus that illustrate how numerous sRNAs and associated proteins are embedded in complex networks of regulation. In addition, we discuss the CRISPR-Cas systems defined as an RNA-interference-like mechanism, which also exist in staphylococcal strains.

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Discovered in the 1980s, small regulatory RNAs (sRNAs) are now considered key actors in virtually all aspects of bacterial physiology and virulence. Together with transcriptional and translational regulatory proteins, they integrate and often are hubs of complex regulatory networks, responsible for bacterial response/adaptation to various perceived stimuli. The recent development of powerful RNA sequencing technologies has facilitated the identification and characterization of sRNAs (length, structure and expression conditions) and their RNA targets in several bacteria. Nevertheless, it could be very difficult for non-experts to understand the advantages and drawbacks related to each offered option and, consequently, to make an informed choice. Therefore, the main goal of this review is to provide a guide to navigate through the twists and turns of high-throughput RNA sequencing technologies, with a specific focus on those applied to the study of sRNAs.

L. monocytogenes causes listeriosis, a foodborne disease that is particularly dangerous for immunocompromised individuals and fetuses. Several virulence factors of this bacterial pathogen belong to a family of leucine-rich repeat (LRR)-containing proteins called internalins. Among these, InlP is known for its role in placental infection. We report here a function of InlP in mammalian cell nucleus organization. We demonstrate that bacteria do not produce InlP under in vitro culture conditions. When ectopically expressed in human cells, InlP translocates into the nucleus and changes the morphology of nuclear speckles, which are membrane-less organelles storing splicing factors. Using yeast two-hybrid screen, immunoprecipitation and pull-down experiments, we identify the tumor suppressor and splicing factor RBM5 as a major nuclear target of InlP. InlP inhibits RBM5-induced cell death and stimulate the formation of RBM5-induced nuclear granules, where the SC35 speckle protein redistributes. Taken together, these results suggest that InlP acts as a nucleomodulin controlling compartmentalization and function of RBM5 in the nucleus and that L. monocytogenes has developed a mechanism to target the host cell splicing machinery.

30Pathogenic bacteria must rapidly adapt to ever-changing environmental signals or nutrient 31 availability resulting in metabolism remodeling. The carbon catabolite repression represents 32 a global regulatory system, allowing the bacteria to express genes involved in carbon 33 utilization and metabolization of the preferred carbon source. In Staphylococcus aureus, 34 regulation of catabolite repressing genes is mediated by the carbon catabolite protein A 35 (CcpA). Here, we have identified a CcpA-dependent small non-coding RNA, RsaI that is 36 inhibited by high glucose concentrations. RsaI represses the translation of mRNAs encoding 37 a major permease of glucose uptake, the FN3K enzyme that protects proteins against 38 damages caused by high glucose concentrations, and IcaR, the transcriptional repressor of 39 exopolysaccharide production. Besides, RsaI regulates the activities of other sRNAs 40 responding to the uptake of glucose-6 phosphate or NO. Finally, RsaI inhibits the expression 41 of several enzymes involved in carbon catabolism pathway, and activates genes involved in 42 energy production, fermentation and NO detoxification when the glucose concentration 43 decreases. This multifunctional RNA provides a signature for a metabolic switch when 44 glucose is scarce and growth is arrested. 45 46 47 48All bacteria require a carbon source, providing energy for their growth, division, and for the 49 synthesis of all macromolecules. Besides, pathogenic bacteria during the infectious process 50 of the host, must cope with hostile conditions such as nutrient deficiency, temperature, 51 oxidative and osmotic shocks, and must overcome innate immune responses. For instance, 52Staphylococcus aureus uses carbohydrates to grow under high NO and anaerobiosis (Vitko 53 et al., 2016). To survive in these complex environments and to counteract the host defense, 54 S. aureus produces a plethora of virulence factors. The synthesis of these factors is fine-55 tuned by intricate interactions between multiple regulators involving both proteins and RNAs 56 (Novick, 2003). Additionally, biosynthetic intermediates, generated from the central 57 metabolism of S. aureus, have strong impacts on the synthesis of virulence factors. Besides, 58 several metabolite-sensing regulatory proteins (CcpA, CodY, Rex and RpiR) act as key 59 regulatory factors to coordinate the synthesis of genes involved in metabolic pathways, in 60 stress responses, and in pathogenesis (Somerville and Proctor, 2009; Richardson et al., 61 2015). Through the adaptation of the metabolism of the bacteria to specific host 62 microenvironment, these proteins contribute to S. aureus pathogenesis (Richardson et al., 63 2015). 64Among these proteins, the carbon catabolite protein A (CcpA) acts as a catabolite 65 regulator, allowing the bacteria to use the preferred carbon source (i.e., glucose) in a 66 hierarchical manner (Seidl et al., 2008a;Seidl et al., 2009). CcpA belongs to the LacI 67 repressor family and binds to a specific DNA sequence, called the cre ...

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