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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*
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/drug therapy
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
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*
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/drug therapy