Search

34 páginas, 13 figuras, Recurrent tuberculosis occurs due to exogenous reinfection or reactivation/persistence. We analysed 90 sequential MDR Mtb isolates obtained in Argentina from 27 patients with previously diagnosed MDR-TB that recurred in 2018 (1-10 years, 2-10 isolates per patient). Three long-term predominant strains were responsible for 63% of all MDR-TB recurrences. Most of the remaining patients were infected by strains different from each other. Reactivation/persistence of the same strain caused all but one recurrence, which was due to a reinfection with a predominant strain. One of the prevalent strains showed marked stability in the recurrences, while in another strain higher SNP-based diversity was observed. Comparisons of intra- versus inter-patient SNP distances identified two possible reinfections with closely related variants circulating in the community. Our results show a complex scenario of MDR-TB infections in settings with predominant MDR Mtb strains., This work was supported by the ERANet-LAC (TRANS-TB-TRANS Project ELAC2015/T08-0664), the ISCIII (AC16/00057, 15/01554, 16/01449, 18/00599, 19/00331 and contract number MS15/00075) and the ANPCyT (grant number PICT-2016-3219). The authors are grateful to Dainora Jaloveckas (cienciatraducida.com) for editing and proofreading assistance.

Transcriptional and proteomic profiling of individual cells have revolutionized interpretation of biological phenomena by providing cellular landscapes of healthy and diseased tissues1,2. These approaches, however, do not describe dynamic scenarios in which cells continuously change their biochemical properties and downstream 'behavioural' outputs3-5. Here we used 4D live imaging to record tens to hundreds of morpho-kinetic parameters describing the dynamics of individual leukocytes at sites of active inflammation. By analysing more than 100,000 reconstructions of cell shapes and tracks over time, we obtained behavioural descriptors of individual cells and used these high-dimensional datasets to build behavioural landscapes. These landscapes recognized leukocyte identities in the inflamed skin and trachea, and uncovered a continuum of neutrophil states inside blood vessels, including a large, sessile state that was embraced by the underlying endothelium and associated with pathogenic inflammation. Behavioural screening in 24 mouse mutants identified the kinase Fgr as a driver of this pathogenic state, and interference with Fgr protected mice from inflammatory injury. Thus, behavioural landscapes report distinct properties of dynamic environments at high cellular resolution. This study was supported by RTI2018-095497-B-I00 from Ministerio de Ciencia e Innovación (MCIN), HR17_00527 from Fundación La Caixa, Transatlantic Network of Excellence (TNE-18CVD04) from the Leducq Foundation, and FET-OPEN (no. 861878) from the European Commission to A.H. M.P-S. is supported by a Federation of European Biochemical Societies and the EMBO ALTF (no. 1142-2020) long-term fellowships. J.S. is supported by a fellowship (PRE2019-089130) from MICINN and A.A.-C. is supported by fellowship CF/BQ/ DR19/11740022 from La Caixa Foundation. J.L.Y.L. was supported by A*STAR and a Juan de la Cierva JCI-2017-33136 Fellowship from MICINN. S.D.C. is a recipient of a Marie Sklodowska-Curie fellowship (749731). M.G. is supported by SAF2017-89116R-P from MCIN and HR18_00120 from la Fundación La Caixa. T.R.M. is supported by grant NIH AI163223, L.G.N. is supported by SIgN core funding from A*STAR, and G.F.C. is supported by MCIN/ AEI/10.13039/501100011033 (grant PID2019-110895RB-I00) and by Junta de Comunidades de Castilla-La Mancha (SBPLY/19/180501/000211). F.S.-C. is supported by MCIN (grant RTI2018- 102084-B-I00), O.S. is supported by the Leducq Foundation (TNE-18CVD04), F.D.-d.-M. is supported by MCIN (TEC2017-84395-P), and T.E.S. is supported by the National Cancer Institute, NIH grant CA233576. The CNIC is supported by the MCIN and the Pro-CNIC Foundation. Sí