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Fulltext First Whole-Genome Sequence of Mycobacterium iranicum, a Newly Reported Mycobacterial Species

Tan JL, Ng HF, Wee WY, Ang MY, Wong GJ, Ngeow YF, et al.

Genome Announc, 2013;1(5).
PMID: 24072861 DOI: 10.1128/genomeA.00732-13

Mycobacterium iranicum is a new species of nontuberculous mycobacterium reported in 2013. Here, we describe the first whole-genome sequence of this species, that of M. iranicum strain UM_TJL, isolated from a patient in Malaysia.

Matched MeSH terms: Nontuberculous Mycobacteria
Meningitis due to atypical Mycobacteria

CHAN KE, PATHMANATHAN T

Med J Malaya, 1961 Mar;15:113-6.
PMID: 13878004
Matched MeSH terms: Nontuberculous Mycobacteria*
Fulltext Interferon-β controls non-tuberculous mycobacterial infection in mice

Norazmi MN

Virulence, 2017 10 03;8(7):1085-1087.
PMID: 28605283 DOI: 10.1080/21505594.2017.1341035
Matched MeSH terms: Nontuberculous Mycobacteria*
Five-year species distribution and antimicrobial susceptibility of non-tuberculous mycobacteria in Malaysia, 2018-2022

Mohamad Azranyi M, Aziz ZA, Ishak D, Mohd Nais NF, Elias ZA, Sulaiman NAF, et al.

J Med Microbiol, 2024 Feb;73(2).
PMID: 38380521 DOI: 10.1099/jmm.0.001809

Introduction. Non-tuberculous Mycobacteria (NTM) is a group of mycobacteria distinct from the Mycobacterium tuberculosis complex. They can cause opportunistic infections, especially in immunocompromised individuals.Gap Statement. Over the last few years, there has been a growing concern regarding the distribution and antimicrobial resistance of NTM in Malaysia. however, a comprehensive study to fully grasp the NTM situation has yet to be conducted.Aim. This study aimed to investigate the species distribution and antimicrobial susceptibility patterns of NTM isolated from clinical samples in Malaysia from 2018 to 2022.Methodology. A retrospective analysis was conducted on NTM isolates obtained from various clinical specimens over a span of five years. The isolates were identified using phenotypic and molecular techniques, and antimicrobial susceptibility profiles for clinically significant isolates were determined using minimum inhibitory concentration.Results. The study revealed a diverse distribution of NTM species in Malaysia, with Mycobacteroides abscessus complex and Mycobacterium avium complex emerging as the most predominant. Furthermore, the antimicrobial susceptibility patterns showed varying degrees of resistance to commonly used antibiotics, highlighting the significance of treatment tailored to susceptibility testing results.Conclusion. This study provides valuable perspective into the epidemiology of NTM in Malaysia. The information gained from this study should prove useful for empirically treating serious NTM infections prior to species identification and the availability of antimicrobial susceptibility testing results.

Matched MeSH terms: Nontuberculous Mycobacteria*
Prevalence and Characteristics of Non-tuberculous Mycobacteria (NTM) Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation: a Systematic Review and Meta-analysis

Cinicola BL, Ottaviano G, Hashim IF, Zainudeen ZT, Hamid IJA, Elfeky R

J Clin Immunol, 2023 Dec 22;44(1):23.
PMID: 38129624 DOI: 10.1007/s10875-023-01615-3

PURPOSE: Non-tuberculous mycobacteria (NTM) infections in hematopoietic stem cell transplantation (HSCT) recipients represent a diagnostic and therapeutic challenge. Here, we aimed to review and analyze current literature on incidence, clinical presentation, and outcome of NTM infection after allogeneic HSCT.
METHODS: We performed a systematic review and meta-analysis of available literature regarding NTM infection in children and adults receiving allogeneic HSCT.
RESULTS: We identified 56 articles eligible for the analysis. Among 15 studies, describing 15,798 allogeneic HSCT, we estimated a prevalence of 1.26% (95% CI 0.72, 1.93) of NTM after transplant. Analysis of 175 patients with NTM infection showed a median time of diagnosis of 318 days after HSCT, an increased prevalence in adults (82.9%), and a most frequent pulmonary involvement (44%). Comparison between children and adults revealed an earlier post-transplant disease onset (median 130 days vs 287 days) and most frequent non-pulmonary presentation in children. A vast heterogeneity of therapeutic approach reflected the lack of universal recommendations regarding drug combination and duration of therapy. Overall, NTM-related mortality accounted for 33% in this systematic review.
CONCLUSION: Although rare, NTM infections can complicate post-transplant course with a high mortality rate in children and adults. The lack of prospective studies and guidelines prevents identification of risk factors and therapeutic recommendations.

Matched MeSH terms: Nontuberculous Mycobacteria*
Fulltext MabsBase: a Mycobacterium abscessus genome and annotation database

Heydari H, Wee WY, Lokanathan N, Hari R, Mohamed Yusoff A, Beh CY, et al.

PLoS One, 2013;8(4):e62443.
PMID: 23658631 DOI: 10.1371/journal.pone.0062443

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.

Matched MeSH terms: Nontuberculous Mycobacteria/classification; Nontuberculous Mycobacteria/genetics*; Nontuberculous Mycobacteria/isolation & purification
Fulltext Whole-Genome Shotgun Sequencing of Mycobacterium abscessus M156, an Emerging Clinical Pathogen in Malaysia

Choo SW, Wong YL, Beh CY, Lokanathan N, Leong ML, Ong CS, et al.

Genome Announc, 2013 Jan;1(1).
PMID: 23405341 DOI: 10.1128/genomeA.00063-12

Mycobacterium abscessus is an emerging clinical pathogen commonly associated with non-tuberculous mycobacterial infections. We report herein the draft genome of M. abscessus strain M156.

Matched MeSH terms: Nontuberculous Mycobacteria
Fulltext Identification of new genomospecies in the Mycobacterium terrae complex

Ngeow YF, Wong YL, Tan JL, Hong KW, Ng HF, Ong BL, et al.

PLoS One, 2015;10(4):e0120789.
PMID: 25830768 DOI: 10.1371/journal.pone.0120789

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.

Matched MeSH terms: Nontuberculous Mycobacteria/classification; Nontuberculous Mycobacteria/genetics*; Nontuberculous Mycobacteria/isolation & purification*
Fulltext Genomic Comparisons Reveal Microevolutionary Differences in Mycobacterium abscessus Subspecies

Tan JL, Ng KP, Ong CS, Ngeow YF

Front Microbiol, 2017;8:2042.
PMID: 29109707 DOI: 10.3389/fmicb.2017.02042

Mycobacterium abscessus, a rapid-growing non-tuberculous mycobacterium, has been the cause of sporadic and outbreak infections world-wide. The subspecies in M. abscessus complex (M. abscessus, M. massiliense, and M. bolletii) are associated with different biologic and pathogenic characteristics and are known to be among the most frequently isolated opportunistic pathogens from clinical material. To date, the evolutionary forces that could have contributed to these biological and clinical differences are still unclear. We compared genome data from 243 M. abscessus strains downloaded from the NCBI ftp Refseq database to understand how the microevolutionary processes of homologous recombination and positive selection influenced the diversification of the M. abscessus complex at the subspecies level. The three subspecies are clearly separated in the Minimum Spanning Tree. Their MUMi-based genomic distances support the separation of M. massiliense and M. bolletii into two subspecies. Maximum Likelihood analysis through dN/dS (the ratio of number of non-synonymous substitutions per non-synonymous site, to the number of synonymous substitutions per synonymous site) identified distinct genes in each subspecies that could have been affected by positive selection during evolution. The results of genome-wide alignment based on concatenated locally-collinear blocks suggest that (a) recombination has affected the M. abscessus complex more than mutation and positive selection; (b) recombination occurred more frequently in M. massiliense than in the other two subspecies; and (c) the recombined segments in the three subspecies have come from different intra-species and inter-species origins. The results lead to the identification of possible gene sets that could have been responsible for the subspecies-specific features and suggest independent evolution among the three subspecies, with recombination playing a more significant role than positive selection in the diversification among members in this complex.

Matched MeSH terms: Nontuberculous Mycobacteria
Fulltext Genomic Analysis of Mycobacterium massiliense strain M115, an isolate from human sputum

Ngeow YF, Wong YL, Lokanathan N, Wong GJ, Ong CS, Ng KP, et al.

J Bacteriol, 2012 Sep;194(17):4786.
PMID: 22887681 DOI: 10.1128/JB.01104-12

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.

Matched MeSH terms: Nontuberculous Mycobacteria/classification; Nontuberculous Mycobacteria/genetics*; Nontuberculous Mycobacteria/isolation & purification
Fulltext Complete genome sequence and comparative genomic analysis of Mycobacterium massiliense JCM 15300 in the Mycobacterium abscessus group reveal a conserved genomic island MmGI-1 related to putative lipid metabolism

Sekizuka T, Kai M, Nakanaga K, Nakata N, Kazumi Y, Maeda S, et al.

PLoS One, 2014;9(12):e114848.
PMID: 25503461 DOI: 10.1371/journal.pone.0114848

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.

Matched MeSH terms: Nontuberculous Mycobacteria/genetics*
Mycobacterium brisbanense species nova isolated from a patient with chronic cavitary lung infection

Poh ME, Liam CK, Ng KP, Tan R

Chest, 2014 Apr;145(4):858-860.
PMID: 24687707 DOI: 10.1378/chest.13-1952

We describe the first case, to our knowledge, of Mycobacterium brisbanense species nova with the type strain W6743T (=ATCC 49938T=DSM 44680T) isolated from the lungs of a man with a 6-month history of productive cough and intermittent fever presenting with acute hypoglycemia. A CT scan of the thorax revealed multiple small nodules and consolidation over both lungs with cavitation. Sputum culture repeatedly grew M brisbanense species nova, a novel species never before isolated in Malaysia. The case met the American Thoracic Society criteria for the diagnosis of nontuberculous mycobacterial infection. There was dramatic clinical and radiologic response to treatment with an empirical combination of rifampicin, ethambutol, and levofloxacin and subsequently clarithromycin and levofloxacin once sensitivity was known. This report is the first, to our knowledge, of the pathogen isolated in a patient with chronic cavitary lung infection since it was first identified from an antral sinus in Brisbane, Queensland, Australia, and the first time it is isolated from a human subject in Malaysia.

Matched MeSH terms: Nontuberculous Mycobacteria/isolation & purification*
Fulltext Isolation of atypical mycobacteria from clinical material in Malaysia

Khor SY, Jegathesan M

Med J Malaysia, 1983 Jun;38(2):158-60.
PMID: 6621448

During the period 1979-1982, 70 strains of atypical mycobacteria isolated from clinical material were identified as belonging to species or species complex. Twenty-eight out of 61 strains isolated from pulmonary specimens were identified as M. avium-intracellulare. This frequency of association of M. avium-intracellulare with sputa of patients with pulmonary symptoms points to its potential importance and the need for further investigation.

Matched MeSH terms: Nontuberculous Mycobacteria/isolation & purification*
Fulltext Draft Genome Sequence of Mycobacterium massiliense Strain M159, Showing Phenotypic Resistance to β-Lactam and Tetracycline Antibiotics

Ngeow YF, Leong ML, Wong YL, Wong GJ, Tan JL, Wee WY, et al.

Genome Announc, 2013;1(4).
PMID: 23990576 DOI: 10.1128/genomeA.00669-13

Mycobacterium massiliense is a nontuberculous mycobacterium associated with human infections. We report here the draft genome sequence of M. massiliense strain M159, isolated from the bronchial aspirate of a patient who had a pulmonary infection. This strain showed genotypic and in vitro resistance to a number of tetracyclines and beta-lactam antibiotics.

Matched MeSH terms: Nontuberculous Mycobacteria
Fulltext Comparative Genomic Analysis Reveals a Possible Novel Non-Tuberculous Mycobacterium Species with High Pathogenic Potential

Choo SW, Dutta A, Wong GJ, Wee WY, Ang MY, Siow CC

PLoS One, 2016;11(4):e0150413.
PMID: 27035710 DOI: 10.1371/journal.pone.0150413

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.

Matched MeSH terms: Nontuberculous Mycobacteria/genetics*; Nontuberculous Mycobacteria/isolation & purification*; Nontuberculous Mycobacteria/pathogenicity
Fulltext Annotated genome sequence of Mycobacterium massiliense strain M154, belonging to the recently created taxon Mycobacterium abscessus subsp. bolletii comb. nov

Choo SW, Wong YL, Tan JL, Ong CS, Wong GJ, Ng KP, et al.

J Bacteriol, 2012 Sep;194(17):4778.
PMID: 22887675 DOI: 10.1128/JB.01043-12

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.

Matched MeSH terms: Nontuberculous Mycobacteria/classification; Nontuberculous Mycobacteria/genetics*; Nontuberculous Mycobacteria/isolation & purification
A Comparative Genomics Approach for Shortlisting Broad-Spectrum Drug Targets in Nontuberculous Mycobacteria

Swain A, Gnanasekar P, Prava J, Rajeev AC, Kesarwani P, Lahiri C, et al.

Microb Drug Resist, 2021 Feb;27(2):212-226.
PMID: 32936741 DOI: 10.1089/mdr.2020.0161

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.

Matched MeSH terms: Nontuberculous Mycobacteria/drug effects*; Nontuberculous Mycobacteria/genetics*
Fulltext Mycobacterium abscessus - to treat or not to treat

Pang YK, Ngeow YF, Wong YL, Liam CK

Respirol Case Rep, 2013 Dec;1(2):31-3.
PMID: 25473536 DOI: 10.1002/rcr2.17

A patient with Mycobacterium abscessus lung disease was mistaken to have pulmonary tuberculosis with airway colonization by the non-tuberculous mycobacterium. Appropriate antibiotics were only given when the patient's signs and symptoms worsened while on anti-tuberculosis therapy. Despite treatment with a combination of antibiotics showing in vitro susceptibility, the pathogen persisted in the respiratory secretions for longer than 6 months and the patient suffered a spontaneous pneumothorax 14 months into treatment. This case illustrates the chronic course of M. abscessus lung infection, the tendency for flare-ups, the inadequacy of current treatment regimens, and the necessity for prolonged patient follow-up.

Matched MeSH terms: Nontuberculous Mycobacteria
Fulltext Phylogenomics of Brazilian epidemic isolates of Mycobacterium abscessus subsp. bolletii reveals relationships of global outbreak strains

Davidson RM, Hasan NA, de Moura VC, Duarte RS, Jackson M, Strong M

Infect Genet Evol, 2013 Dec;20:292-7.
PMID: 24055961 DOI: 10.1016/j.meegid.2013.09.012

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.

Matched MeSH terms: Nontuberculous Mycobacteria/classification*; Nontuberculous Mycobacteria/genetics; Nontuberculous Mycobacteria/isolation & purification
Fulltext Antibiotic resistance in Mycobacterium Abscessus and Mycobacterium Fortuitum isolates from Malaysian patients

Jayasingam SD, Zin T, Ngeow YF

Int J Mycobacteriol, 2017 11 25;6(4):387-390.
PMID: 29171453 DOI: 10.4103/ijmy.ijmy_152_17

BACKGROUND: Rapidly growing mycobacterial species (RGM) are increasingly being recognized as the cause of various superficial and deep infections in humans. Two of the species most frequently isolated from clinical specimens are Mycobacterium abscessus and Mycobacterium fortuitum. Both species are associated with antibiotic resistances that may complicate therapy. This paper describes the pattern of resistance to five antibiotics commonly prescribed for RGM infections, in M. abscessus and M. fortuitum isolated from Malaysian patients.
METHODS: The bacterial strains studied were examined with Etest strips to determine their minimum inhibitory concentrations (MICs) toward amikacin, ciprofloxacin, clarithromycin, imipenem, and linezolid.
RESULTS: Among 51 M. abscessus isolates examined by the Etest, the overall MICs of ciprofloxacin, imipenem, amikacin, clarithromycin, and linezolid showed resistance rates of 33.3%, 31.4%, 2.0%, 5.9%, and 21.6%, to the five antibiotics, respectively. M. abscessus subspecies abscessus was more resistant than M. abscessus subsp. massilience to ciprofloxacin, imipenem, and linezolid but was more susceptible to clarithromycin and amikacin. M. fortuitum isolates were significantly less resistant than M. abscessus to ciprofloxacin (3.6%) and imipenem (7.1%) but more resistant to clarithromycin (42.9%) and linezolid (39.3%).
CONCLUSION: A suitable combination therapy for Malaysian patients would be amikacin plus clarithromycin and ciprofloxacin, to cover infections by all three M. abscessus subspecies and M. fortuitum.

Matched MeSH terms: Nontuberculous Mycobacteria/drug effects*; Nontuberculous Mycobacteria/isolation & purification; Nontuberculous Mycobacteria/physiology

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