The gap gene of Rhizobium etli is required for both free life and symbiosis with common beans.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH or Gap) is a ubiquitous enzyme essential for carbon and energy metabolism in most organisms. Despite its primary role in sugar metabolism, GAPDH is recognized for its involvement in diverse cellular processes, being considered a paradigm among multifunctional/moonlighting proteins. Besides its canonical cytoplasmic location, GAPDH has been detected on cell surfaces or as a secreted protein in prokaryotes, yet little is known about its possible roles in plant symbiotic bacteria. Here we report that Rhizobium etli, a nitrogen-fixing symbiont of common beans, carries a single gap gene responsible for both GAPDH glycolytic and gluconeogenic activities. An active Gap protein is required throughout all stages of the symbiosis between R. etli and its host plant Phaseolus vulgaris. Both glycolytic and gluconeogenic Gap metabolic activities likely contribute to bacterial fitness during early and intermediate stages of the interaction, whereas GAPDH gluconeogenic activity seems critical for nodule invasion and nitrogen fixation. Although the R. etli Gap protein is secreted in a c-di-GMP related manner, no involvement of the R. etli gap gene in c-di-GMP related phenotypes, such as flocculation, biofilm formation or EPS production, was observed. Notably, the R. etli gap gene fully complemented a double gap1/gap2 mutant of Pseudomonas syringae for free life growth, albeit only partially in planta, suggesting potential specific roles for each type of Gap protein. Nevertheless, further research is required to unravel additional functions of the R. etli Gap protein beyond its essential metabolic roles.

Artritis reumatoidea asociada a colangitis biliar primaria bajo tratamiento con medicamentos biológicos. Reporte de 4 casos y puesta al día / Rheumatoid arthritis associated with primary biliary cholangitis under treatment with biological drugs. Report of 4 cases and update

El abordaje terapéutico de pacientes con dos o más enfermedades autoinmunes es un verdadero desafío, especialmente cuando el tratamiento enfocado en una de ellas podría precipitar la progresión de la otra. Si bien la asociación de artritis reumatoidea (AR) con colangitis biliar primaria (CBP) no es tan frecuente, cuando coexisten, la utilización de metotrexato u otras drogas hepatotóxicas debe decidirse con cautela. Con la indicación más generalizada de las drogas biológicas modificadoras del curso de la AR (DMARb) han aparecido algunos reportes de pacientes con AR y CBP tratados con etanercept, infliximab, rituximab, tocilizumab y abatacept. Presentamos una serie de casos de 4 pacientes con AR y CBP que fueron tratados con DMARb. Nuestro reporte sería el primero en describir dos casos con golimumab para controlar la AR y el segundo en reportar un caso con adalimumab y otro con abatacept. Con rituximab, ya existen tres casos publicados. En ninguno de los pacientes de nuestra serie empeoraron los síntomas de CBP y, al contrario, en dos de ellos hubo mejoría de los parámetros bioquímicos. En conclusión, según lo observado y lo reportado en la literatura, el uso DMARb podría ser considerado en el caso de pacientes con AR activa que además padecen CBP

The therapeutic approach of patients with two or more autoimmune diseases is quite a challenge, especially when the treatment of one of them, can precipitate the progression of the other. Even though the association of rheumatoid arthritis (RA) and primary biliary cholangitis (PBC) is rare; when both coexist, the use of methotrexate and other hepatotoxic drugs should be used with caution. With a most widespread indication of biologic diseasemodifying antirheumatic drugs (bDMARDs) some reports of patients with RA and PBC treated with etanercept, infliximab, rituximab, tocilizumab and abatacept have been published. We report a case series that includes 4 patients with RA and PBC treated with bDMARDs. This is the first report to describe two cases in which golimumab was used to control RA and the second to report patients who received adalimumab and abatacept. Three cases of patients treated with rituximab have been published to date. None of the patients of our report suffered a progression of their PBC; matter in fact, two of them showed an improvement in their biochemical parameters. PBC symptoms did not get worse in any of the patients. On the contrary, laboratory parameters improved in two of the four patients. In conclusion, according to the literature reviewed and to our findings, the use of bDMARDs could be considered in RA patients with concomitant PBC