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Nucleotide-based signaling molecules (NSMs) are widespread in bacteria and eukaryotes, where they control important physiological and behavioral processes. In bacteria, NSM-based regulatory networks are highly complex, entailing large numbers of enzymes involved in the synthesis and degradation of active signaling molecules. How the converging input from multiple enzymes is transformed into robust and unambiguous cellular responses has remained unclear. Here we show that Escherichia coli converts dynamic changes of c-di-GMP into discrete binary signaling states, thereby generating heterogeneous populations with either high or low c-di-GMP. This is mediated by an ultrasensitive switch protein, PdeL, which senses the prevailing cellular concentration of the signaling molecule and couples this information to c-di-GMP degradation and transcription feedback boosting its own expression. We demonstrate that PdeL acts as a digital filter that facilitates precise developmental transitions, confers cellular memory, and generates functional heterogeneity in bacterial populations to evade phage predation. Based on our findings, we propose that bacteria apply ultrasensitive regulatory switches to convert dynamic changes of NSMs into binary signaling modes to allow robust decision-making and bet-hedging for improved overall population fitness., bioRxiv

Reconociendo el carácter furibundo del surgimiento de las ciencias sociales, en este escrito nos proponemos la necesidad de problematizar la propia práctica de conocimiento y su implicancia en los diversos mecanismos de poder del que resultan-generan-reproducen. Más específicamente,realizamos un análisis, en clave de ejercicio arqueológico y genealógico, sobre nuestro trabajo colectivo y sobre nosotros/as mismos/as en tanto sujetos de la academia, a partir de la lectura que hemos hecho de la obra foucaultiana desde el año 2008 e ininterrumpidamente hasta la actualidad. Retomamos el modo en que nos ha interpelado, nutrido y modificado dicha lectura, así como también caracterizamos el escenario intelectual y político en el que se gesta nuestra inquietud, aquellas preocupaciones que nos han impulsado a conformarnos en colectivo político y, atento a ello, a la imperiosa necesidad de revisar el herramental que la obra foucaultiana brinda.Reconociendo que, en líneas generales, los sistemas académicos y los recorridos que se proponen para sus estudiantes, para los/as becarios/as de diversas instituciones y para sus trabajadores/as son prioritariamente de carácter individual, reafirmamos la importancia de construir colectivos de trabajo al interior del ámbito académico, como un gesto de resistencia a lógicas de neoliberalización que permean el campo. Recognizing the furious character of the emergence of the social sciences, in this paper we propose the need to problematize the practice of knowledge itself and its implication in the various mechanisms of power that result-generate-reproduce. More specifically, we perform an analysis, in the key of archaeological and genealogical exercise, on our collective work and on ourselves as subjects of the academy, based on the reading we have done of the Foucaultian work since 2008 And uninterrupted until today. We return to the way in which this reading has been questioned, nurtured and modified, as well as characterize the intellectual and political scenario in which our concern is generated, those preoccupations that have impelled us to conform ourselves in political group and, The imperative need to review the tooling that Foucauld’s work provides. Recognizing that, in general terms, the academic systems and the courses proposed for their students, for the scholarship holders of various institutions and for their workers are primarily of an individual nature, we reaffirm the importance of constructing working groups Within the academic sphere, as a gesture of resistance to neoliberalization logics that permeate the field. Fil: Brizuela, Florencia Agustina. Universidad Nacional de Rosario. Facultad de Ciencias Políticas y Relaciones Internacionales. Instituto de Investigaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina Fil: Campana, Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Políticas y Relaciones Internacionales. Instituto de Investigaciones; Argentina Fil: Giavedoni, Jose Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Políticas y Relaciones Internacionales. Instituto de Investigaciones; Argentina Fil: Ginga, Luciana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Políticas y Relaciones Internacionales. Instituto de Investigaciones; Argentina Fil: Manfredi, Pablo Andrés. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina Fil: Servio, Mariana. Universidad Nacional de Rosario. Facultad de Ciencias Políticas y Relaciones Internacionales. Instituto de Investigaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina

Here is presented the complete 2,571,405-bp genome sequence of Capnocytophaga canimorsus strain 5 (Cc5), a strain that was isolated from a fatal septicaemia. Phylogenetic analysis of conserved genes supports the inclusion of C. canimorsus into the Cytophaga-Flavobacteria-Bacteroides (CFB) phylum and indicates close relationships with environmental flavobacteria as Flavobacterium johnsoniae and Gramella forsetii. In addition, relative phylogenetic topology of Capnocytophaga species shows that C. canimorsus share more sequence similarities with human host associated Capnocytophaga species than species from the latter group among themselves (e.g. C. gingivalis and C. ochracea). As compared to other Capnocytophaga, C.canimorsus seems to have differentiated by large-scale horizontal gene transfer compensated by gene losses. Consistently with a relatively reduced genome size, genome scale metabolic modelling suggested a reduced global pleiotropy as it is illustrated by the presence of a split TCA cycle or by the metabolic uncoupling of the hexoses and N-acetylhexosamines pathways. In addition and in agreement with the high content in HCO3- and Na+ ions in saliva, we predicted a CO2-dependent fumarate respiration coupled to a Na+ ions gradient based respiratory chain in Cc5. All together these observations draw the picture of an organism with a high degree of specialization to a relatively homeostatic host environment. Unexpectedly, the genome of Cc5 did not encode classical complex virulence functions as T3SSs or T4SSs. However it exhibits a very high relative number of predicted surface-exposed lipoproteins. Many of them are encoded within 13 different putative polysaccharide utilization loci (PULs), a hallmark of the CFB group, discovered in the gut commensal Bacteroides thetaiotaomicron. When Cc5 bacteria were grown on Hek293 cells, at least 12 PULs were expressed and detected by mass spectrometry. Semi-quantitative analysis of the Cc5 surfome identified 73 surface exposed proteins among which 40 were lipoproteins and accounted for 76% of the total quantification. Interestingly, 28 proteins (38%) were encoded by 9 different PULs and corresponded to more than 54% of total MS-flying peptides detected. A systematic knockout analysis of the 13 PULs revealed that 6 PULs are involved in growth during cell culture infections with most dramatic effect observed for ΔPUL5. Proteins encoded by PUL5, one of the most abundant PULs (12%), turned out to be devoted to foraging glycans from N-linked glycoproteins as fetuin but also IgG. It was not only essential for growth on cells but also for survival in mice and in fresh human serum therefore representing a new type of virulence factor. Further characterization of the PUL5 deglycosylation mechanism revealed that deglycosylation is achieved by a large surface complex spanning the outer membrane and consisting of five PUL5 encoded Gpd proteins and the Siac sialidase. GpdCDEF contribute to the binding of glycoproteins at the bacterial surface while GpdG is a β-endo-glycosidase cleaving the N-linked oligosaccharide after the first N-linked GlcNAc residue. We demonstrate that GpdD, -G, -E and -F are surface-exposed outer membrane lipoproteins while GpdC resembles a TonB-dependent OM transporter and presumably imports oligosaccharides into the periplasm after cleavage from glycoproteins. Terminal sialic acid residues of the oligosaccharide are then removed by SiaC in the periplasm. Finally, degradation of the oligosaccharide proceeds sequentially from the desialylated non reducing end by the action of periplasmic exoglycosidases, including β-galactosidases, β-N-Acetylhexosaminidases and α-mannosidases. Genome sequencing of additional C. canimorsus strains have been performed with the only use of second generation sequencing methods (Solexa and 454). Two assembling approaches were developed in order to enhance assembly capacities of pre-existing tools. Draft assemblies of the three pathogenic human blood isolates C. canimorsus 2 (three contigs), C. canimorsus 11 (152 contigs) and C. canimorsus 12 (63 contigs) are presented here. Comparative genomics including genomes of four available human hosted Capnocytophaga species stressed C. canimorsus exclusively conserved features as an oxidative respiratory chain and an oxidative stress resistance or the presence of a Cc5 specific PULs content. Therefore we propose these features as potential factors involved in the pathogenesis of C. canimorsus.