Diagnostic Microbiology and Infectious Disease 94 (2019) 248–254 Contents lists available at ScienceDirect Diagnostic Microbiology and Infectious Disease journal homepage: www.elsevier.com/locate/diagmicrobio Mycobacteriology Current significance of the Mycobacterium chelonae-abscessus group Robert S. Jones, Kileen L. Shier, Ronald N. Master, Jian R. Bao, Richard B. Clark ⁎ Infectious Disease Department, Quest Diagnostics Nichols Institute, Chantilly, VA 20131 article info abstract Article history: Organisms of the Mycobacterium chelonae-abscessus group can be significant pathogens in humans. They produce Received 19 April 2018 a number of diseases including acute, invasive and chronic infections, which may be difficult to diagnose cor- Received in revised form 30 January 2019 rectly. Identification among members of this group is complicated by differentiating at least eleven (11) Accepted 31 January 2019 known species and subspecies and complexity of identification methodologies. Treatment of their infections Available online 10 February 2019 may be problematic due to their correct species identification, antibiotic resistance, their differential susceptibil- ity to the limited number of drugs available, and scarcity of susceptibility testing. Keywords: Mycobacterium chelonae-abscessus group © 2019 Elsevier Inc. All rights reserved. Mycobacterium abscessus group Infections produced by Mycobacterium chelonae-abscessus group 1. Introduction 2. Taxonomy The Mycobacterium chelonae-abscessus group (MC-AG) is composed The taxonomy of the MC-AG has undergone a number of revisions of a group of organisms that continue to gain notoriety by producing over recent years with at least 11 species and subspecies recognized disease in humans. The spectrum of individual species and subspecies (Table 1). M. chelonae was first recognized as a species in 1923 producing increased types and numbers of infections is predominately (Bergey, 1923) and was described in more detail in 1972 (Stanford due both to greater awareness and to more accurate methods of identi- et al., 1972), while M. abscessus was established in 1953 (Moore and fication. MC-AG may produce severe infections which can be difficult to Frerichs, 1953)(Table 1). The taxonomic future of the M. abscessus treat because of their high levels of antibiotic resistance. The group may be the most debated issue among acid-fast bacilli re- M. abscessus group undoubtedly shows both a greater pathogenic po- searchers during the next few years (Bryant et al., 2016; Leao et al., tential and antibiotic resistance as compared to its counterpart, the 2009, 2011; Sassi and Drancourt, 2014). It is unclear whether the mem- M. chelonae group. Identification to the subspecies level and detection bers of the M. abscessus group will eventually be classified as a subspe- of the erythromycin ribosomal methylase (erm) (41) gene may be re- cies or as a full species. quired for some M. abscessus group infections due to the differential an- tibiotic resistance found in these 3 different subspecies. This review 3. Natural habitats of MC-AG provides an overview of the pathogenic burden of the MC-AG while fo- cusing on the more virulent M. abscessus group. Infections caused by Members of the MC-AG are opportunistic pathogens that are normal other members of the MC-AG are reviewed in Table 1. inhabitants of the environment (Halstrom et al., 2015). Humans are be- lieved to be infected through exposure to environmental sources (Falkinham III, 2002). It has been thought that humans are not a source Abbreviations: NTM, nontuberculous mycobacteria; MTB, Mycobacterium tuberculosis; of infection; however, a recent study suggests indirect transmission Mycobacterium chelonae group, Mycobacterium chelonae subsp. chelonae, Mycobacterium among cystic fibrosis patients may occur and that transmission through chelonae subsp. bovis and Mycobacterium chelonae subsp. gwanakae; MC-AG, Mycobacte- aerosols may be possible (Bryant et al., 2016). rium chelonae-abscessus group; M. abscessus group, includes Mycobacterium abscessus subsp. abscessus, subsp. massiliense, and subsp. bolletii (for the purposes of this review, Water is thought to be the most common source of infection. Rapidly we have adopted the subspecies as the correct nomenclature). Note: Species-level identi- growing mycobacteria, including members of the MC-AG, have been fication of the M. abscessus group and the M. chelonae group is not consistent in the litera- found in surface salt water and fresh water sources throughout the ture therefore, unless the organisms are clearly identified as a specificspecies,the world (Appelgren et al., 2008; Covert et al., 1999; Gruft et al., 1981; organism name is denoted as a group.; MALDI-TOF, matrix-assisted laser desorption ioni- van Ingen et al., 2009). They are also thought to be present in most mu- zation time-of-flight mass spectrometry. ⁎ Corresponding author. Tel.: +1-703-802-7067. nicipal water sources (Chang et al., 2002; Primm et al., 2004). Their E-mail address: [email protected] (R.B. Clark). presence in public water sources is due in part to their high chlorine https://doi.org/10.1016/j.diagmicrobio.2019.01.021 0732-8893/© 2019 Elsevier Inc. All rights reserved. Table 1 Members of the MC-AG (Parte, 2018). Organism Type strain with references* Macrolide resistance mechanisms Pathogenic potential and infections produced Identification methods Antibiotic susceptibility Mycobacterium abscessus ATCC 19977T Erm (41) gene: macrolide Opportunist: most virulent of the MC-AG M. chelonae complex vs. M. abscessus Amikacin: 90–100% subsp. abscessus =CIP 104536T = DSM resistance chronic respiratory disease (Jarand et al., complex: Cefoxitin: 7–75% 944196T = may be induced or produced 2011; Roux et al., 2009), skin and soft HPLC, MALDI-TOF successful for Clarithromycin: 79–100% JCM 13569T (Kusunoki and when either subspecies contain tissue (Galil et al., 1999; Liu et al., 2013; identification; Clofazimine: N90% Ezaki, 1992; Moore and this gene; alternate macrolide Uslan et al., 2006) for the subspeciation of M. abscessus complex Tigecycline: 100% Frerichs, 1953) resistance gene for both skeletal and disseminated infections MALDI-TOF is variable (Body et al., 2018; (van Ingen et al., 2012) Mycobacterium abscessus CIP 108n541T = CCUG 50184T subspecies is the gene rrl. (possibly catheter-related) Fangous et al., 2014; Girard et al., 2016; subsp. bolletii (Adekambi et al., 2006) (Brown-Elliott & Wallace, 2005a; Kodana et al., 2016; Mather et al., 2014; Mycobacterium abscessus CIP 108297T = CCUG Nonfunctional, truncated erm Apiwattankul et al., 2015; Hibi et al., Mediavilla-Gradolph et al., 2015; subsp. massiliense* 48898T (Adekambi et al., 2004) (41); 2017; Mooren et al., 2017)* Suzuki et al., 2015). *Some authorities gene may also contain the *Most published studies on infections R.S. Jones et al. / Diagnostic Microbiology and Infectious Disease 94 (2019) 248 recognize M. functional macrolide resistance do not distinguish between the Definitive identification of the M. abscessus massiliense gene, A2058G/C three subspecies subsp. organisms: sequencing gene targets as a full species including (rpoB), hsp65, sodA, and/or ITS region. 16S rRNA is not successful (Macheras et al., 2009; Ringuet et al., 1999). Other target genes are needed to definitely identify other MC-AG organisms (see below) Mycobacterium ATCC 35752T = CCUG 47445T = No detectable erm gene; may Opportunist: 2nd most virulent See above Amikacin: 78–100% chelonae subsp. CIP 104535T = DSM 43804T= harbor the alternate resistance member of the MAC group Cefoxitin: 5–67% chelonae JCM 6388T (Bergey, 1923; gene, rrl A2058G/C Skin and soft tissue (Kennedy et al., 2012) Clarithromycin: 49–89% Stanford et al., 1972) Eye infections: 2nd leading type Clofazimine: 90% of infection (Moorthy et al., 2012) Tigecycline: 23–27% Chronic respiratory disease, (uncommon (van Ingen et al., 2012) as compared to M. abscessus) (Griffith et al., 1993): found in cystic fibrosis disease, Skeletal (Wallace et al., 1992) Disseminated infection is associated with organ transplants, diabetes mellitus, malignancy, long-term corticosteroid administrational, immunosuppressant therapy, and tumor necrosis factor-alpha (TNF-α) inhibitors – (Griffith et al., 2007). 254 Catheter-related infections (Song et al., 2012) Mycobacterium ATCC 35752T(=CCUG 47445T = No documentation of inducible Likely cattle pathogen Distinctive MALDI-TOF profile as compared Similar clarithromycin chelonae subsp. bovis CIP 104535T = DSM 43804T = clarithromycin resistance to M. chelonae subspecies chelonae) susceptibility pattern as JCM 6388T = NCTC 946T) and (Kim et al., 2017) (Kim et al., 2017); sequencing of 16S M. chelonae subsp. chelonae QIA-37T (=KCTC 39630T = rRNA, hsp65, and rpoB indicates that M. JCM 30986T) chelonae subsp. bovis is closely related to (Kim et al., 2017) M. chelonae subsp. chelonae (Kim et al., 2017). Mycobacterium MOTT36WT = KCTC 29127T = No documentation of inducible Unknown; potential opportunist; Have different MALDI-TOF profiles from More resistant to various chelonae subsp. JCM 32454T (Kim et al., 2018) clarithromycin resistance isolates recovered from sputum those of M. chelonae subsp. chelonae and antibiotics than M. chelonae gwanakae (Kim et al., 2018) samples (Kim et al., 2018) M. chelonae subsp. bovis subsp. chelonae except for (continued on next page) 249 250 Table 1 (continued) Organism Type strain with references* Macrolide resistance mechanisms Pathogenic potential and infections produced Identification methods