Person: Iturbe Sanz, Pablo
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Iturbe Sanz
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Pablo
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Ciencias de la Salud
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0000-0002-0981-4444
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811806
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Publication Open Access Noncontiguous operon atlas for the Staphylococcus aureus genome(Oxford University Press, 2024) Iturbe Sanz, Pablo; San Martín Bernal, Álvaro; Hamamoto, Hiroshi; Marcet Houben, Marina; Galbaldón, Toni; Solano Goñi, Cristina; Lasa Uzcudun, Íñigo; Ciencias de la Salud; Osasun Zientziak; Universidad Pública de Navarra / Nafarroako Unibertsitate PublikoaBacteria synchronize the expression of genes with related functions by organizing genes into operons so that they are cotranscribed together in a single polycistronic messenger RNA. However, some cellular processes may benefit if the simultaneous production of the operon proteins coincides with the inhibition of the expression of an antagonist gene. To coordinate such situations, bacteria have evolved noncontiguous operons (NcOs), a subtype of operons that contain one or more genes that are transcribed in the opposite direction to the other operon genes. This structure results in overlapping transcripts whose expression is mutually repressed. The presence of NcOs cannot be predicted computationally and their identification requires a detailed knowledge of the bacterial transcriptome. In this study, we used direct RNA sequencing methodology to determine the NcOs map in the Staphylococcus aureus genome. We detected the presence of 18 NcOs in the genome of S. aureus and four in the genome of the lysogenic prophage 80α. The identified NcOs comprise genes involved in energy metabolism, metal acquisition and transport, toxin–antitoxin systems, and control of the phage life cycle. Using the menaquinone operon as a proof of concept, we show that disarrangement of the NcO architecture results in a reduction of bacterial fitness due to an increase in menaquinone levels and a decrease in the rate of oxygen consumption. Our study demonstrates the significance of NcO structures in bacterial physiology and emphasizes the importance of combining operon maps with transcriptomic data to uncover previously unnoticed functional relationships between neighbouring genes.Publication Open Access Bacteriophages avoid autoimmunity from cognate immune systems as an intrinsic part of their life cycles(Nature Research, 2024) Rostøl, Jakob T.; Quiles Puchalt, Nuria; Iturbe Sanz, Pablo; Lasa Uzcudun, Íñigo; Penadés, José R.; Ciencias de la Salud; Osasun ZientziakDormant prophages protect lysogenic cells by expressing diverse immune systems, which must avoid targeting their cognate prophages upon activation. Here we report that multiple Staphylococcus aureus prophages encode Tha (tail-activated, HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain-containing anti-phage system), a defence system activated by structural tail proteins of incoming phages. We demonstrate the function of two Tha systems, Tha-1 and Tha-2, activated by distinct tail proteins. Interestingly, Tha systems can also block reproduction of the induced tha-positive prophages. To prevent autoimmunity after prophage induction, these systems are inhibited by the product of a small overlapping antisense gene previously believed to encode an excisionase. This genetic organization, conserved in S. aureus prophages, allows Tha systems to protect prophages and their bacterial hosts against phage predation and to be turned of during prophage induction, balancing immunity and autoimmunity. Our results show that the fne regulation of these processes is essential for the correct development of prophages’ life cycle.Publication Embargo Noncontiguous operon atlas in Staphylococcus aureus(2023) Iturbe Sanz, Pablo; Lasa Uzcudun, Íñigo; Ciencias de la Salud; Osasun ZientziakIn previous work from the group, we described the existence of a new transcriptional architecture that we call a noncontiguous operon (NcO). NcOs consist of groups of genes that are transcribed on the same RNA molecule, although genes that are transcribed in the opposite direction separate them. The mRNA of the gene transcribed in the opposite direction is full-length complementary and therefore antisense to the mRNA of the operon. Unlike classical operons, whose presence in the genome is predicted based on theoretical criteria of proximity between genes and biological function of the encoded proteins, the presence of NcOs cannot be determined theoretically and it is necessary to resort to transcriptomic analyses to demonstrate the co-transcription of non-contiguous groups of genes. As a continuation of this line of research, in this thesis we decided to determine the map of NcOs present in the genome of a bacterium. This information would allow us to know the abundance of this transcriptional architecture and thus analyze whether they have common elements or related functions. We decided to use Staphylococcus aureus as a model for four reasons: (I) it is the bacterium in which we first described this transcriptional architecture, (II) we had transcriptomic data obtained from the Illumina platform that could be useful in our study, (III) we have experience in its genetic manipulation and (IV) it has enormous clinical relevance due to its versatility as a pathogen and the existence of multidrug-resistant bacteria.