Genomic Insights into the Emerging Human Pathogen Mycobacterium massiliense.
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.
- SourceAvailable from: Nabeeh Hasan[Show abstract] [Hide abstract]
ABSTRACT: Nontuberculous mycobacterial (NTM) infections caused by Mycobacterium abscessus are responsible for a range of disease manifestations from pulmonary to skin infections and are notoriously difficult to treat due to innate resistance to many antibiotics. Previous population studies of clinical M. abscessus utilized multi locus sequence typing or pulsed field gel electrophoresis, but high resolution examinations of the genetic diversity at the whole genome level has not been well characterized, particularly among clinical isolates derived in the United States (US). We performed whole genome sequencing of eleven clinical M. abscessus isolates derived from eight US patients with pulmonary NTM infections, compared them to 30 globally diverse clinical isolates and investigated intra-patient genomic diversity and evolution. Phylogenomic analyses revealed a cluster of closely related US and Western European-derived M. abscessus ssp. abscessus isolates that are genetically distinct from other European and all Asian isolates. Large-scale variation analyses suggested genome content differences of 0.3 - 8.3% relative to the reference strain, ATCC 19977(T). Longitudinally sampled isolates showed very few single nucleotide polymorphisms and correlated genomic deletion patterns suggesting homogenous infection populations. Our study explores the genomic diversity of clinical M. abscessus strains from multiple continents, and provides insight into the genome plasticity of an opportunistic pathogen.Journal of Clinical Microbiology 07/2014; · 4.23 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Mycobacterium abscessus is an emerging cause of respiratory disease and soft tissue infections. Whole genome sequencing and other molecular approaches are enhancing our understanding of outbreaks, antibiotic resistance mechanisms, and virulence properties, and of the phylogeny of the M. abscessus complex. Infection models are providing further insights into factors such as colony phenotype that impact host-pathogen interactions. This paper reviews recent developments in our understanding of genetic variation in M. abscessus and the potential relevance for disease and treatment.Tuberculosis (Edinburgh, Scotland) 12/2013; 93:S15–S20. · 2.54 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Three recently sequenced strains isolated from patients during an outbreak of Mycobacterium abscessus subsp. massiliense infections at a cystic fibrosis center in the United States were compared with 6 strains from an outbreak at a cystic fibrosis center in the United Kingdom and worldwide strains. Strains from the 2 cystic fibrosis outbreaks showed high-level relatedness with each other and major-level relatedness with strains that caused soft tissue infections during an epidemic in Brazil. We identified unique single-nucleotide polymorphisms in cystic fibrosis and soft tissue outbreak strains, separate single-nucleotide polymorphisms only in cystic fibrosis outbreak strains, and unique genomic traits for each subset of isolates. Our findings highlight the necessity of identifying M. abscessus to the subspecies level and screening all cystic fibrosis isolates for relatedness to these outbreak strains. We propose 2 diagnostic strategies that use partial sequencing of rpoB and secA1 genes and a multilocus sequence typing protocol.Emerging Infectious Diseases 03/2014; 20(3):364-71. · 7.33 Impact Factor
Genomic Insights into the Emerging Human Pathogen Mycobacterium
Hervé Tettelin,aElizabeth P. Sampaio,b,cSean C. Daugherty,aErin Hine,aDavid R. Riley,aLisa Sadzewicz,aNaomi Sengamalay,a
Kent Shefchek,aQi Su,aLuke J. Tallon,aPatricia Conville,dKenneth N. Olivier,bSteven M. Holland,bClaire M. Fraser,a
and Adrian M. Zelaznyb,d
Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USAa; Laboratory of
Clinical Infectious Diseases, LCID, NIAID, NIH, Bethesda, Maryland, USAb; Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazilc; and Microbiology
Service, Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, Maryland, USAd
Mycobacterium massiliense (Mycobacterium abscessus group) is an emerging pathogen causing pulmonary disease and skin and
ease. M. abscessus includes three closely related organisms, Myco-
bacterium abscessus (sensu stricto), Mycobacterium massiliense,
and Mycobacterium bolletii, with taxonomic status under debate.
Interest in M. massiliense arose following recent postsurgical in-
patients (1, 5).
The genomes of three M. abscessus strains and of M. bolletii
have been released (2–4, 6) and constitute an important resource
ent 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 cumu-
lative size of 5,195,205 bp and a 64.1% G?C content. It contains
total coding sequences, while the rest were found to be hypothet-
ical or conserved hypothetical proteins.
A phylogenetic tree based on core genome single nucleotide
polymorphisms (SNPs) that was derived from a whole-genome
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,
iense type strain and 47J26 have the reported 2-nucleotide (CG)
deletion and the large 276-nucleotide (nt) deletion in the induc-
ible 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. massil-
iense-specific genes revealed that 128 of these genes, including 2
genes encoding virulence-related WXG/ESAT-6 family proteins,
an ?120-kb genomic region (108 genes) in CCUG 48898, encod-
47J26. Most of these genes, including genes encoding virulence
2 M. abscessus genomes but mostly present (100 of 108) in M.
None of the recently released genomes include the 23-kb mer-
cury resistance plasmid found in M. abscessus (6).
A detailed genomic study promises a better understanding of
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
Institute of Allergy and Infectious Diseases, National Institutes of Health,
Department of Health and Human Services, under contract number
1. Aitken ML, et al. 2012. Respiratory outbreak of Mycobacterium abscessus
subspecies massiliense in a lung transplant and cystic fibrosis center. Am. J.
Respir. Crit. Care Med. 185:231–232.
2. Chan J, Halachev M, Yates E, Smith G, Pallen M. 2012. Whole-genome
3. Choi GE, et al. 2012. Draft genome sequence of Mycobacterium abscessus
subsp. bolletii BD(T). J. Bacteriol. 194:2756–2757.
4. Choo SW, et al. 2012. Genome sequence of the Mycobacterium abscessus
strain M93. J. Bacteriol. 194:3278.
5. Leao SC, et al. 2010. Epidemic of surgical-site infections by a single clone
of rapidly growing mycobacteria in Brazil. Future Microbiol. 5:971–980.
6. Ripoll F, et al. 2009. Non mycobacterial virulence genes in the genome of
the emerging pathogen Mycobacterium abscessus. PLoS One 4:e5660. doi:
Received 9 July 2012 Accepted 17 July 2012
Address correspondence to Hervé Tettelin, email@example.com.
Copyright © 2012, American Society for Microbiology. All Rights Reserved.
jb.asm.orgJournal of Bacteriology p. 5450 October 2012 Volume 194 Number 19