MyMedR

Fulltext Genomic reconnaissance of clinical isolates of emerging human pathogen Mycobacterium abscessus reveals high evolutionary potential

Choo SW, Wee WY, Ngeow YF, Mitchell W, Tan JL, Wong GJ, et al.

Sci Rep, 2014;4:4061.

PMID: 24515248 DOI: 10.1038/srep04061

Mycobacterium abscessus (Ma) is an emerging human pathogen that causes both soft tissue infections and systemic disease. We present the first comparative whole-genome study of Ma strains isolated from patients of wide geographical origin. We found a high proportion of accessory strain-specific genes indicating an open, non-conservative pan-genome structure, and clear evidence of rapid phage-mediated evolution. Although we found fewer virulence factors in Ma compared to M. tuberculosis, our data indicated that Ma evolves rapidly and therefore should be monitored closely for the acquisition of more pathogenic traits. This comparative study provides a better understanding of Ma and forms the basis for future functional work on this important pathogen.

Matched MeSH terms: Mycobacterium Infections/microbiology*; Mycobacterium Infections/pathology

Fulltext Lady Windermere syndrome: an inappropriate eponym for an increasingly important condition

Kasthoori JJ, Liam CK, Wastie ML

Singapore Med J, 2008 Feb;49(2):e47-9.

PMID: 18301826

Non-tuberculous mycobacterial infection (NMI) occurs in elderly women with no pre-existing lung disease, and this has been termed the Lady Windermere syndrome. NMIs are increasing in prevalence and an increasing number of pulmonary mycobacterial infections is due to non-tuberculous mycobacteria. The diagnosis is often difficult because the organism is not readily isolated or cultured, and the condition may not be considered by the radiologist. We report NMI in a 64-year-old woman, based on clinical and radiological findings. Although termed the Lady Windermere syndrome, the name does not correspond to the character in Oscar Wilde's play; hence the eponym is not widely used.

Matched MeSH terms: Mycobacterium Infections, Nontuberculous/drug therapy; Mycobacterium Infections, Nontuberculous/pathology*; Mycobacterium Infections, Nontuberculous/radiography

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: Mycobacterium Infections, Nontuberculous/microbiology*

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: Mycobacterium Infections, Nontuberculous/microbiology*; Mycobacterium Infections, Nontuberculous/epidemiology*

An immunodiffusion analysis of strains of Mycobacterium ulcerans isolated in Australia, Malaya, Mexico, Uganda and Zaire

Stanford JL

J Med Microbiol, 1973 Aug;6(3):405-8.

PMID: 4199273

Matched MeSH terms: Mycobacterium Infections/immunology

Heterogeneity of mycolactones produced by clinical isolates of Mycobacterium ulcerans: implications for virulence

Mve-Obiang A, Lee RE, Portaels F, Small PL

Infect Immun, 2003 Feb;71(2):774-83.

PMID: 12540557

Mycobacterium ulcerans is the causative agent of Buruli ulcer, a severe necrotizing skin disease endemic in tropical countries. Clinical evidence suggests that M. ulcerans isolates from Asia, Mexico, and Australia may be less virulent than isolates from Africa. In vivo studies suggest that mycolactone, a polyketide-derived macrolide toxin, plays a major role in the tissue destruction and immune suppression which occur in cases of Buruli ulcer. Mycolactones were extracted from 34 isolates of M. ulcerans representing strains from Africa, Malaysia, Asia, Australia, and Mexico. Thin-layer chromatography, mass spectroscopic analysis, and cytopathic assays of partially purified mycolactones from these isolates revealed that M. ulcerans produces a heterogeneous mixture of mycolactone variants. Mycolactone A/B, the most biologically active mycolactone species, was identified by mass spectroscopy as [M(+)Na](+) at m/z 765.5 in all cytotoxic isolates except for those from Mexico. Mycolactone C [M+Na](+) at m/z 726.3 was the dominant mycolactone species in eight Australian isolates, and mycolactone D [M+Na](+) m/z 781.2 was characteristic of two Asian strains. Mycolactone species are conserved within specific geographic areas, suggesting that there may be a correlation between mycolactone profile and virulence. In addition, the core lactone, [M+Na](+) m/z 447.4, was identified as a minor species, supporting the hypothesis that mycolactones are synthesized by two polyketide synthases. A cytopathic assay of the core lactone showed that this molecule is sufficient for cytotoxicity, although it is much less potent than the complete mycolactone.

Matched MeSH terms: Mycobacterium Infections, Nontuberculous/microbiology*

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: Mycobacterium Infections, Nontuberculous/diagnosis; Mycobacterium Infections, Nontuberculous/microbiology*

Fulltext Concurrent mycobacterial infection and non-Hodgkin's lymphoma at the same site in an AIDS patient

Kenali MS, Fadzilah I, Maizaton AA, Sani A

Med J Malaysia, 2004 Mar;59(1):108-11.

PMID: 15535345

A 31 years old Chinese male with acquired immunodeficiency syndrome (AIDS) presented with concurrent mycobacterial infection and a synchronous non-Hodgkin's lymphoma of the nose. The diagnoses were made over a period of two months. Treatment for the mycobacterial infection was administered but he succumbed to the disease shortly after the diagnosis of NHL was established. This was an unusual case where two pathologies occurred in the same site in a patient with AIDS.

Matched MeSH terms: Mycobacterium Infections/complications*; Mycobacterium Infections/diagnosis

Sensitivity to tuberculin, PPD-B and histoplasmin in the population of Sabah in East Malaysia

Roy RN

Med J Aust, 1971 Feb 06;1(6):317-21.

PMID: 5546216

Matched MeSH terms: Mycobacterium Infections/diagnosis

Bilateral nontuberculous mycobacterial middle ear infection: a rare case

Tang IP, Singh S, Rajagopalan R

Ear Nose Throat J, 2014 Sep;93(9):390-4.

PMID: 25255345

Nontuberculous Mycobacterium (NTM) middle ear infection is a rare cause of chronic bilateral intermittent otorrhea. We report a rare case of bilateral NTM middle ear infection in which a 55-year-old woman presented with intermittent otorrhea of 40 years' duration. The patient was treated medically with success. We conclude that NTM is a rare but probably under-recognized cause of chronic otitis media. A high index of suspicion is needed for the diagnosis to avoid prolonged morbidity. Treatment includes surgical clearance of infected tissue with appropriate antimycobacterial drugs, which are selected based on culture and sensitivity.

Matched MeSH terms: Mycobacterium Infections, Nontuberculous/diagnosis*; Mycobacterium Infections, Nontuberculous/drug therapy; Mycobacterium Infections, Nontuberculous/pathology; Mycobacterium Infections, Nontuberculous/surgery

Non-tuberculous mycobacterium bacteraemia in a pregnant systemic lupus erythematosus (SLE) patient: a case review and pooled case analysis

Shaharir SS, Sulaiman Sahari N, Mohamed Fuad Z, Zukiman WZHW, Mohd Yusof NH, Sulong A, et al.

Clin Rheumatol, 2018 Mar;37(3):837-847.

PMID: 28971307 DOI: 10.1007/s10067-017-3855-7

Non-tuberculous mycobacteria (NTM) are recognized as an important cause of human diseases and infections. It is commonly known to cause infections of the skin, soft tissue infections, and pulmonary infection as well as bacteraemia. We report a challenging case of severe mycobacterium abscessus bacteraemia in a pregnant lady with active systemic lupus erythematous (SLE). A comprehensive literature review of NTM infection among SLE patients was also performed, and pooled analysis of the reported cases, including our case, was done to determine the clinical characteristics and factors associated with poor outcome of NTM infection.

Matched MeSH terms: Mycobacterium Infections, Nontuberculous/complications*; Mycobacterium Infections, Nontuberculous/drug therapy

Fulltext Differences in virulence and immune response induced in a murine model by isolates of Mycobacterium ulcerans from different geographic areas

Ortiz RH, Leon DA, Estevez HO, Martin A, Herrera JL, Romo LF, et al.

Clin Exp Immunol, 2009 Aug;157(2):271-81.

PMID: 19604267 DOI: 10.1111/j.1365-2249.2009.03941.x

Buruli ulcer (BU) is the third most common mycobacterial disease in immunocompetent hosts. BU is caused by Mycobacterium ulcerans, which produces skin ulcers and necrosis at the site of infection. The principal virulence factor of M. ulcerans is a polyketide-derived macrolide named mycolactone, which has cytotoxic and immunosuppressive activities. We determined the severity of inflammation, histopathology and bacillary loads in the subcutaneous footpad tissue of BALB/c mice infected with 11 different M. ulcerans isolates from diverse geographical areas. Strains from Africa (Benin, Ghana, Ivory Coast) induced the highest inflammation, necrosis and bacillary loads, whereas the strains collected from Australia, Asia (Japan, Malaysia, New Guinea), Europe (France) and America (Mexico) induced mild inflammation. Subsequently, animals were infected with the strain that exhibited the highest (Benin) or lowest (Mexico) level of virulence in order to analyse the local immune response generated. The Mexican strain, which does not produce mycolactone, induced a predominantly T helper type 1 (Th1) cytokine profile with constant high expression of the anti-microbial peptides beta defensins 3 and 4, in co-existence with low expression of the anti-inflammatory cytokines interleukin (IL)-10, IL-4 and transforming growth factor (TGF)-beta. The highly virulent strain from Benin which produces mycolactone A/B induced the opposite pattern. Thus, different local immune responses were found depending on the infecting M. ulcerans strain.

Matched MeSH terms: Mycobacterium Infections, Nontuberculous/immunology

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: Mycobacterium Infections, Nontuberculous/drug therapy*; Mycobacterium Infections, Nontuberculous/microbiology

Meningitis due to atypical Mycobacteria

CHAN KE, PATHMANATHAN T

Med J Malaya, 1961 Mar;15:113-6.

PMID: 13878004

Matched MeSH terms: Mycobacterium Infections*

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: Mycobacterium Infections, Nontuberculous

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: Mycobacterium Infections, Nontuberculous/drug therapy*; Mycobacterium Infections, Nontuberculous/microbiology

Fulltext Molecular typing of Mycobacterium abscessus based on tandem-repeat polymorphism

Wong YL, Ong CS, Ngeow YF

J Clin Microbiol, 2012 Sep;50(9):3084-8.

PMID: 22760048 DOI: 10.1128/JCM.00753-12

A variable-number tandem-repeat (VNTR) typing assay for the differentiation of Mycobacterium abscessus strains was developed. This assay showed complete reproducibility, locus stability, and a discriminatory power (Hunter-Gaston discriminatory index [HGDI] of 0.9563) that is superior to that of multilocus sequencing. It is a promising tool for the investigation of Mycobacterium abscessus epidemiology and nosocomial outbreaks.

Matched MeSH terms: Mycobacterium Infections, Nontuberculous/microbiology

Fulltext Draft genome sequence of Mycobacterium bolletii strain M24, a rapidly growing mycobacterium of contentious taxonomic status

Wong YL, Choo SW, Tan JL, Ong CS, Ng KP, Ngeow YF

J Bacteriol, 2012 Aug;194(16):4475.

PMID: 22843600 DOI: 10.1128/JB.00916-12

The whole-genome sequence of Mycobacterium bolletii M24, isolated from the bronchoalveolar lavage fluid of a Malaysian patient, is reported here. The circular chromosome of 5,507,730 bp helped to clarify the taxonomic position of this organism within the M. abscessus complex and revealed the presence of proteins potentially important for pathogenicity in a human host.

Matched MeSH terms: Mycobacterium Infections, Nontuberculous/microbiology

Fulltext Genome sequence of the Mycobacterium abscessus strain M93

Choo SW, Wong YL, Yusoff AM, Leong ML, Wong GJ, Ong CS, et al.

J Bacteriol, 2012 Jun;194(12):3278.

PMID: 22628507 DOI: 10.1128/JB.00492-12

Mycobacterium abscessus is a rapid-growing species of nontuberculous mycobacteria that is frequently associated with opportunistic infections in humans. We report herein the draft genome sequence of M. abscessus strain M93.

Matched MeSH terms: Mycobacterium Infections, Nontuberculous/microbiology

Analysis of the genome of Mycobacterium abscessus strain M94 reveals an uncommon cluster of tRNAs

Choo SW, Wong YL, Leong ML, Heydari H, Ong CS, Ng KP, et al.

J Bacteriol, 2012 Oct;194(20):5724.

PMID: 23012295

Mycobacterium abscessus is a species of rapidly growing nontuberculous mycobacteria that is frequently associated with opportunistic infections in humans. Here, we report the annotated genome sequence of M. abscessus strain M94, which showed an unusual cluster of tRNAs.

Matched MeSH terms: Mycobacterium Infections, Nontuberculous/microbiology

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