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<p><italic>Mycobacterium abscessus</italic> is an emerging rapidly growing mycobacterium (RGM) causing a pseudotuberculous lung disease to which patients with cystic fibrosis (CF) are particularly susceptible. We report here its complete genome sequence. The genome of <italic>M. abscessus</italic> (CIP 104536T) consists of a 5,067,172-bp circular chromosome including 4920 predicted coding sequences (CDS), an 81-kb full-length prophage and 5 IS elements, and a 23-kb mercury resistance plasmid almost identical to pMM23 from <italic>Mycobacterium marinum</italic>. The chromosome encodes many virulence proteins and virulence protein families absent or present in only small numbers in the model RGM species <italic>Mycobacterium smegmatis</italic>. Many of these proteins are encoded by genes belonging to a “mycobacterial” gene pool (e.g. PE and PPE proteins, MCE and YrbE proteins, lipoprotein LpqH precursors). However, many others (e.g. phospholipase C, MgtC, MsrA, ABC Fe(3+) transporter) appear to have been horizontally acquired from distantly related environmental bacteria with a high G+C content, mostly actinobacteria (e.g. <italic>Rhodococcus</italic> sp., <italic>Streptomyces</italic> sp.) and pseudomonads. We also identified several metabolic regions acquired from actinobacteria and pseudomonads (relating to phenazine biosynthesis, homogentisate catabolism, phenylacetic acid degradation, DNA degradation) not present in the <italic>M. smegmatis</italic> genome. Many of the “non mycobacterial” factors detected in <italic>M. abscessus</italic> are also present in two of the pathogens most frequently isolated from CF patients, <italic>Pseudomonas aeruginosa</italic> and <italic>Burkholderia cepacia</italic>. This study elucidates the genetic basis of the unique pathogenicity of <italic>M. abscessus</italic> among RGM, and raises the question of similar mechanisms of pathogenicity shared by unrelated organisms in CF patients.</p>
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