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J Bacteriol. Oct 2012; 194(19): 5450.
PMCID: PMC3457237
Genomic Insights into the Emerging Human Pathogen Mycobacterium massiliense
Hervé Tettelin,corresponding authora Elizabeth P. Sampaio,bc Sean C. Daugherty,a Erin Hine,a David R. Riley,a Lisa Sadzewicz,a Naomi Sengamalay,a Kent Shefchek,a Qi Su,a Luke J. Tallon,a Patricia Conville,d Kenneth N. Olivier,b Steven M. Holland,b Claire M. Fraser,a and Adrian M. Zelaznybd
aInstitute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
bLaboratory of Clinical Infectious Diseases, LCID, NIAID, NIH, Bethesda, Maryland, USA
cLeprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil
dMicrobiology Service, Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, Maryland, USA
corresponding authorCorresponding author.
Address correspondence to Hervé Tettelin, tettelin/at/som.umaryland.edu.
Received July 9, 2012; Accepted July 17, 2012.
Abstract
Mycobacterium massiliense (Mycobacterium abscessus group) is an emerging pathogen causing pulmonary disease and skin and soft tissue infections. We report the genome sequence of the type strain CCUG 48898.
Most nontuberculous mycobacterial respiratory infections are caused by Mycobacterium abscessus or Mycobacterium avium complex in patients with cystic fibrosis or chronic pulmonary disease. M. abscessus includes three closely related organisms, Mycobacterium abscessus (sensu stricto), Mycobacterium massiliense, and Mycobacterium bolletii, with taxonomic status under debate. Interest in M. massiliense arose following recent postsurgical infection outbreaks and a respiratory outbreak among cystic fibrosis patients (1, 5).
The genomes of three M. abscessus strains and of M. bolletii have been released (24, 6) and constitute an important resource to better understand the biology of these pathogens. Here we present the draft genome of the M. massiliense type strain CCUG 48898 and its comparison to the other released genomes. The sequence was obtained using a combination of the 454 Titanium 3-kb paired-end and Illumina HiSeq 2000 100-bp paired-end technologies. The draft genome includes 5 contigs with a cumulative size of 5,195,205 bp and a 64.1% G+C content. It contains 5,193 predicted protein-coding genes, 47 tRNA genes, and 1 rRNA operon. Potential functions were assigned to 66.6% (3,460) of the total coding sequences, while the rest were found to be hypothetical or conserved hypothetical proteins.
A phylogenetic tree based on core genome single nucleotide polymorphisms (SNPs) that was derived from a whole-genome multiple alignment clusters M. abscessus 47J26 with CCUG 48898, while M. abscessus M93 clusters with M. abscessus ATCC 19977 and M. bolletii BD appears separately.
Strain 47J26 carries an A-to-C substitution in the 23S rRNA, presumed to confer clarithromycin resistance. Both the M. massiliense type strain and 47J26 have the reported 2-nucleotide (CG) deletion and the large 276-nucleotide (nt) deletion in the inducible macrolide resistance gene erm41 as well as several shared SNPs. These features and the tree described above indicate that 47J26 is most likely a strain of M. massiliense.
BLASTN-based comparisons (shared genes defined by a BLASTN e value of ≤10−5) revealed 346 and 304 genes that are unique to CCUG 48898 and 47J26, respectively, compared to the other three genomes. A pairwise comparison of these M. massiliense-specific genes revealed that 128 of these genes, including 2 genes encoding virulence-related WXG/ESAT-6 family proteins, are shared by CCUG 48898 and 47J26 while 226 and 188 genes are unique to CCUG 48898 and 47J26, respectively. We also identified an ~120-kb genomic region (108 genes) in CCUG 48898, encoding a beta-lactamase and 7 TetR family regulators, that is absent in 47J26. Most of these genes, including genes encoding virulence factors such as MCE and YrbE family proteins, are absent from the 2 M. abscessus genomes but mostly present (100 of 108) in M. bolletii.
None of the recently released genomes include the 23-kb mercury resistance plasmid found in M. abscessus (6).
A detailed genomic study promises a better understanding of the diseases caused by the M. abscessus group and M. massiliense in particular.
Nucleotide sequence accession number.
The M. massiliense strain CCUG 48898 genome sequence and annotation data have been deposited at NCBI GenBank under the accession number AKVF00000000.
ACKNOWLEDGMENTS
This project has been funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract number HHSN272200900007C.
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