Abbreviations ALI: acute lung injury; ARDS: acute respiratory distress syndrome; BMI: body mass index; CXR: plain chest X-ray film; IBW: ideal body weight; ICU: Intensive Care Unit; LDH: lactate dehydrogenase assay; LOS: length of stay; MV: mechanical ventilation; NIV: non-invasive ventilation; PaO2/FIO2: relation between patient arterial pO 2 and inspired oxygen fraction used; PCV: pressure-controlled ventilation; PEEP: positive end-expiratory pressure; PSV: pressure support ventilation; RR: respiratory rate; RT-PCR: real-time reversetranscriptase-polymerase-chain-reaction; SATI: Argentinian Society of Intensive Care; SOFA: Sequential Organ Failure Assessment; VCV: volumecontrolled ventilation; Vt: tidal volume. Comparative analysis of mycobacterium and related actinomycetes yields insight into the evolution of mycobacterium tuberculosis pathogenesis BACKGROUND: The sequence of the pathogen Mycobacterium tuberculosis (Mtb) strain H37Rv has been available for over a decade, but the biology of the pathogen remains poorly understood. Genome sequences from other Mtb strains and closely related bacteria present an opportunity to apply the power of comparative genomics to understand the evolution of Mtb pathogenesis. We conducted a comparative analysis using 31 genomes from the Tuberculosis Database (TBDB.org), including 8 strains of Mtb and M. bovis, 11 additional Mycobacteria, 4 Corynebacteria, 2 Streptomyces, Rhodococcus jostii RHA1, Nocardia farcinia, Acidothermus cellulolyticus, Rhodobacter sphaeroides, Propionibacterium acnes, and Bifidobacterium longum. RESULTS: Our results highlight the functional importance of lipid metabolism and its regulation, and reveal variation between the evolutionary profiles of genes implicated in saturated and unsaturated fatty acid metabolism. It also suggests that DNA repair and molybdopterin cofactors are important in pathogenic Mycobacteria. By analyzing sequence conservation and gene expression data, we identify nearly 400 conserved noncoding regions. These include 37 predicted promoter regulatory motifs, of which 14 correspond to previously validated motifs, as well as 50 potential noncoding RNAs, of which we experimentally confirm the expression of four. CONCLUSIONS: Our analysis of protein evolution highlights gene families that are associated with the adaptation of environmental Mycobacteria to obligate pathogenesis. These families include fatty acid metabolism, DNA repair, and molybdopterin biosynthesis. Our analysis reinforces recent findings suggesting that small noncoding RNAs are more common in Mycobacteria than previously expected. Our data provide a foundation for understanding the genome and biology of Mtb in a comparative context, and are available online and through TBDB.org. Tuberculosis is still a major killer worldwide, causing an estimated 2-3 million deaths per year [1] . The sequence of the pathogen Mycobacterium tuberculosis (Mtb) strain H37Rv has been available for a decade [2, 3] , but the biology of the pathogen remains poorly understood. Available genome sequences from Mtb strains and other closely related Mycobacteria present an opportunity to bring the power of comparative genomics to the study of Mtb.