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Mycobacterium abscessus is a formidable and difficult-to-treat mycobacterial pathogen with multiple drug-resistance mechanisms. The most important of these mechanisms is the presence of an inducible erythromycin methylase (erm) gene, because it confers macrolide resistance. It has recently been found that "M. abscessus" can be split into three species or subspecies based on gene sequence analysis other than the 16S rRNA gene and the presence or absence of a functional erm(41) gene. Several names have been applied to these three organisms, including M. abscessus or M. abscessus subsp. abscessus, Mycobacterium massiliense or M. abscessus subsp. massiliense, and Mycobacterium bolletii or M. abscessus subsp. bolletii. No universally accepted or recognized species or subspecies designations have emerged, and no names have been universally adopted for these organisms. This uncertainty has led to inconsistencies in the medical literature and understandable confusion by clinicians about the appropriate labels for "M. abscessus" isolates. We discuss the complexities involved in mycobacterial species/subspecies identification and taxonomy and suggest possible ways to improve the present state of uncertainty surrounding the labels for "M. abscessus" clinical isolates. We also suggest necessary changes in mycobacterial laboratory processing and reporting procedures for mycobacterial isolates.

Bedaquiline (BDQ), a diarylquinoline antibiotic that targets ATP synthase, is effective for the treatment of Mycobacterium tuberculosis infections that no longer respond to conventional drugs. While investigating the off-label use of BDQ as salvage therapy, seven of 13 patients with Mycobacterium intracellulare lung disease had an initial microbiological response and then relapsed. Whole-genome comparison of pretreatment and relapse isolates of M. intracellulare uncovered mutations in a previously uncharacterized locus, mmpT5. Preliminary analysis suggested similarities between mmpT5 and the mmpR5 locus, which is associated with low-level BDQ resistance in M. tuberculosis. Both genes encode transcriptional regulators and are adjacent to orthologs of the mmpS5-mmpL5 drug efflux operon. However, MmpT5 belongs to the TetR superfamily, whereas MmpR5 is a MarR family protein. Targeted sequencing uncovered nonsynonymous mmpT5 mutations in isolates from all seven relapse cases, including two pretreatment isolates. In contrast, only two relapse patient isolates had nonsynonymous changes in ATP synthase subunit c (atpE), the primary target of BDQ. Susceptibility testing indicated that mmpT5 mutations are associated with modest 2-to 8-fold increases in MICs for BDQ and clofazimine, whereas one atpE mutant exhibited a 50-fold increase in MIC for BDQ. Bedaquiline shows potential for the treatment of M. intracellulare lung disease, but optimization of treatment regimens is required to prevent the emergence of mmpT5 variants and microbiological relapse.

Laryngeal tuberculosis (TB) was a common manifestation of TB in the early twentieth century, but now represents only 1% of all cases. Most modern case series of laryngeal TB originate outside the USA. We report a case of laryngeal TB from our institution and review other US cases published between 1970 and 2012. One hundred twenty-seven cases were identified. The mean patient age was 49 y and 28% were female. The mean duration of symptoms was 19 weeks. Dysphonia and weight loss were the most common manifestations, seen in 96% and 47% of cases, respectively. These symptoms were usually attributed to malignancy initially. Most cases involved the vocal cords. Eighty-six percent of cases had underlying pulmonary involvement. Mortality was 3%. In the USA, laryngeal TB is rarely suspected and often confused with malignancy. This infection should be considered in patients with unexplained dysphonia and weight loss.

New studies differentiating M. abscessus subsp. abscessus and M. abscessus subsp. massiliense based on the erm(41) gene demonstrate the latter to have a better prognosis and improved treatment outcomes. M. abscessus subsp. abscessus remains a formidable pathogen in diagnosis and treatment.

Mycobacterium terrae complex (MTC) was first characterized in 1981 by the International Working Group in Mycobacterial Taxonomy (IWGMT). The initial MTC consisted of two nonchromogenic slowly growing species: M. terrae and Mycobacterium nonchromogenicum (1, 2). Phenotypic separation within the group was often difficult, and molecular methods were not available, making establishment of species pathogenicity uncertain (3).The complex is recognized as an environmental contaminant of sputum and a cause of tenosynovitis and osteomyelitis primarily of the fingers and wrist (3-35). Whether one or more members of the complex are true respiratory pathogens has not been established (1, 22).The first published case report of tenosynovitis caused by the MTC was by Hirata and Tomiyama in 1976 (4). There have been approximately 34 additional case reports published since then, identified using nonmolecular methods (3-25), with 14 cases identified using molecular methods (26)(27)(28)(30)(31)(32)(33)(34)(35)(36) (Tables 1 and 2). With the exception of four isolates of M. arupense, including the original description of M. arupense (28), details of the methods and/or explicitly stating a 100% 16S rRNA gene sequence identity to recognized species for the remaining cases with molecular identifications have been absent (Table 2).An excellent history and species update of the M. terrae complex based on multigene sequencing targets was published by Tortoli et al. (1). He noted that the presence of a two nucleotide insertion in helix 18 of the 16S rRNA gene (bp ϳ430 to 500; hypervariable region B or region V3) provided a consistent signature sequence for members of the MTC compared to other slowly growing mycobacteria (37,38). He also characterized several new species in the complex, including Mycobacterium heraklionense and Mycobacterium engbaekii (1).The greater availability of DNA sequencing (59) Citation Vasireddy R, Vasireddy S, Brown-Elliott BA, Wengenack NL, Eke UA, Benwill JL, Turenne C, Wallace RJ, Jr. 2016. Mycobacterium arupense, Mycobacterium heraklionense, and a newly proposed species, "Mycobacterium virginiense" sp. nov., but not Mycobacterium nonchromogenicum, as species of the Mycobacterium terrae complex causing tenosynovitis and osteomyelitis.

BACKGROUND: Isolation of Mycobacterium abscessus subspecies abscessus (MAA) is common during Mycobacterium avium complex (MAC) lung disease therapy, but there is limited information about the clinical signifi cance of the MAA isolates.

Bronchiectasis Nontuberculous mycobacterium (NTMnb) infection is an emerging health problem in breast cancer (BCa) patients. We measured sera exosome proteome in BCa-NTMnb subjects and controls by Mass Spectroscopy. Extracellular matrix protein 1 (ECM1) was detected exclusively in the circulating exosomes of 82% of the BCa-NTMnb cases. Co-culture of ECM1+ exosomes with normal human mammary epithelial cells induced epithelial to mesenchymal transition accompanied by increased Vimentin/CDH1 expression ratio and Glutamate production. Co-culture of the ECM1+ exosomes with normal human T cells modulated their cytokine production. The ECM1+ exosomes were markedly higher in sera obtained from BCa-NTMnb subjects. Exclusive expression of APN, APOC4 and AZGP1 was evident in the circulating exosomes of these BCa-NTMnb cases, which predicts disease prevalence independent of the body max index in concert with ECM1. Monitoring ECM1, APN, APOC4 and AZGP1 in the circulating exosomes could be beneficial for risk assessment, monitoring and surveillance of BCa-NTMnb.