Mycobacterium abscessus group subsp., such as M. massiliense, M. abscessus sensu stricto and M. bolletii, are an environmental organism found in soil, water and other ecological niches, and have been isolated from respiratory tract infection, skin and soft tissue infection, postoperative infection of cosmetic surgery. To determine the unique genetic feature of M. massiliense, we sequenced the complete genome of M. massiliense type strain JCM 15300 (corresponding to CCUG 48898). Comparative genomic analysis was performed among Mycobacterium spp. and among M. abscessus group subspp., showing that additional ß-oxidation-related genes and, notably, the mammalian cell entry (mce) operon were located on a genomic island, M. massiliense Genomic Island 1 (MmGI-1), in M. massiliense. In addition, putative anaerobic respiration system-related genes and additional mycolic acid cyclopropane synthetase-related genes were found uniquely in M. massiliense. Japanese isolates of M. massiliense also frequently possess the MmGI-1 (14/44, approximately 32%) and three unique conserved regions (26/44; approximately 60%, 34/44; approximately 77% and 40/44; approximately 91%), as well as isolates of other countries (Malaysia, France, United Kingdom and United States). The well-conserved genomic island MmGI-1 may play an important role in high growth potential with additional lipid metabolism, extra factors for survival in the environment or synthesis of complex membrane-associated lipids. ORFs on MmGI-1 showed similarities to ORFs of phylogenetically distant M. avium complex (MAC), suggesting that horizontal gene transfer or genetic recombination events might have occurred within MmGI-1 among M. massiliense and MAC.
Mycobacterium abscessus is a rapidly growing non-tuberculous mycobacterial species that has been associated with a wide spectrum of human infections. As the classification and biology of this organism is still not well understood, comparative genomic analysis on members of this species may provide further insights on their taxonomy, phylogeny, pathogenicity and other information that may contribute to better management of infections. The MabsBase described in this paper is a user-friendly database providing access to whole-genome sequences of newly discovered M. abscessus strains as well as resources for whole-genome annotations and computational predictions, to support the expanding scientific community interested in M. abscessus research. The MabsBase is freely available at http://mabscessus.um.edu.my.
Members of the Mycobacterium terrae complex are slow-growing, non-chromogenic acid-fast bacilli found in the natural environment and occasionally in clinical material. These genetically closely-related members are difficult to differentiate by conventional phenotypic and molecular tests. In this paper we describe the use of whole genome data for the identification of four strains genetically similar to Mycobacterium sp. JDM601, a newly identified member of the M. terrae complex. Phylogenetic information from the alignment of genome-wide orthologous genes and single nucleotide polymorphisms show consistent clustering of the four strains together with M. sp. JDM601 into a distinct clade separate from other rapid and slow growing mycobacterial species. More detailed inter-strain comparisons using average nucleotide identity, tetra-nucleotide frequencies and analysis of synteny indicate that our strains are closely related to but not of the same species as M. sp. JDM601. Besides the 16S rRNA signature described previously for the M. terrae complex, five more hypothetical proteins were found that are potentially useful for the rapid identification of mycobacterial species belonging to the M. terrae complex. This paper illustrates the versatile utilization of whole genome data for the delineation of new bacterial species and introduces four new genomospecies to add to current members in the M. terrae complex.
We report the draft genome sequence of a clinical isolate, strain M115, identified as Mycobacterium massiliense, a member of the newly created taxon of Mycobacterium abscessus subspecies bolletii comb. nov.
Many members of nontuberculous mycobacteria (NTM) are opportunistic pathogens causing several infections in animals. The incidence of NTM infections and emergence of drug-resistant NTM strains are rising worldwide, emphasizing the need to develop novel anti-NTM drugs. The present study is aimed to identify broad-spectrum drug targets in NTM using a comparative genomics approach. The study identified 537 core proteins in NTM of which 45 were pathogen specific and essential for the survival of pathogens. Furthermore, druggability analysis indicated that 15 were druggable among those 45 proteins. These 15 proteins, which were core proteins, pathogen-specific, essential, and druggable, were considered as potential broad-spectrum candidates. Based on their locations in cytoplasm and membrane, targets were classified as drug and vaccine targets. The identified 15 targets were different enzymes, carrier proteins, transcriptional regulator, two-component system protein, ribosomal, and binding proteins. The identified targets could further be utilized by researchers to design inhibitors for the discovery of antimicrobial agents.
Mycobacteria have been reported to cause a wide range of human diseases. We present the first whole-genome study of a Non-Tuberculous Mycobacterium, Mycobacterium sp. UM_CSW (referred to hereafter as UM_CSW), isolated from a patient diagnosed with bronchiectasis. Our data suggest that this clinical isolate is likely a novel mycobacterial species, supported by clear evidence from molecular phylogenetic, comparative genomic, ANI and AAI analyses. UM_CSW is closely related to the Mycobacterium avium complex. While it has characteristic features of an environmental bacterium, it also shows a high pathogenic potential with the presence of a wide variety of putative genes related to bacterial virulence and shares very similar pathogenomic profiles with the known pathogenic mycobacterial species. Thus, we conclude that this possible novel Mycobacterium species should be tightly monitored for its possible causative role in human infections.
Mycobacterium massiliense has recently been proposed as a member of Mycobacterium abscessus subsp. bolletii comb. nov. Strain M154, a clinical isolate from the bronchoalveolar lavage fluid of a Malaysian patient presenting with lower respiratory tract infection, was subjected to shotgun DNA sequencing with the Illumina sequencing technology to obtain whole-genome sequence data for comparison with other genetically related strains within the M. abscessus species complex.
Rapidly growing, non-tuberculous mycobacteria (NTM) in the Mycobacterium abscessus (MAB) species are emerging pathogens that cause various diseases including skin and respiratory infections. The species has undergone recent taxonomic nomenclature refinement, and is currently recognized as two subspecies, M. abscessus subsp. abscessus (MAB-A) and M. abscessus subsp. bolletii (MAB-B). The recently reported outbreaks of MAB-B in surgical patients in Brazil from 2004 to 2009 and in cystic fibrosis patients in the United Kingdom (UK) in 2006 to 2012 underscore the need to investigate the genetic diversity of clinical MAB strains. To this end, we sequenced the genomes of two Brazilian MAB-B epidemic isolates (CRM-0019 and CRM-0020) derived from an outbreak of skin infections in Rio de Janeiro, two unrelated MAB strains from patients with pulmonary infections in the United States (US) (NJH8 and NJH11) and one type MAB-B strain (CCUG 48898) and compared them to 25 publically available genomes of globally diverse MAB strains. Genome-wide analyses of 27,598 core genome single nucleotide polymorphisms (SNPs) revealed that the two Brazilian derived CRM strains are nearly indistinguishable from one another and are more closely related to UK outbreak isolates infecting CF patients than to strains from the US, Malaysia or France. Comparative genomic analyses of six closely related outbreak strains revealed geographic-specific large-scale insertion/deletion variation that corresponds to bacteriophage insertions and recombination hotspots. Our study integrates new genome sequence data with existing genomic information to explore the global diversity of infectious M. abscessus isolates and to compare clinically relevant outbreak strains from different continents.