Current Molecular Therapeutic Agents and Drug Candidates for Mycobacterium abscessus

Nguyen, Thanh Quang; Jang, Jichan

doi:10.3389/fphar.2021.724725

Cited by 19 publications

(28 citation statements)

References 171 publications

(234 reference statements)

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“…Because of the scarcity of literature on M. senegalense , we draw on treatment guidelines for NTM infections ( 14 , 15 ). From the literature review, we found that the management of NTM infections is quite difficult.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Mycobacterium senegalense Infection After Cholecystectomy

Zhou

Gong

et al. 2022

Front. Public Health

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BackgroundMycobacterium senegalense is a non-tuberculous mycobacterium and is found everywhere in the environment. However, M. senegalense infection in human is extremely rare, especially in immunocompetent individuals. It is difficult to detect M. senegalense infection because its symptoms are non-specific, and routine diagnostic tests are less sensitive. It is also resistant to commonly used antibiotics. Here, we report the first case of M. senegalense infection after laparoscopic cholecystectomy in China.Case PresentationA 55-year-old man was admitted because of repeated infections at multiple incision sites for more than 1 year. Although routine diagnostic test results were negative, metagenomic next-generation sequencing (mNGS) identified DNA sequences of M. senegalense in tissue samples from incision sites. The presence of M. senegalense was further confirmed by polymerase chain reaction and capillary electrophoresis. After 60 days of quadruple therapy with clarithromycin, moxifloxacin, rifampicin, and oxycycline, the patient's wound healed.ConclusionWe believe the case findings contribute to the limited amount of knowledge about M. senegalense infection and raises awareness that this infection can result in poor wound healing, even in an immunocompetent host. Owing to a lack of early, precise diagnosis, it is difficult to treat M. senegalense infections. Based on our findings, mNGS is a sensitive diagnostic test for M. senegalense infections.

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Section: Discussionmentioning

confidence: 99%

Case Report: Mycobacterium senegalense Infection After Cholecystectomy

Zhou

Gong

et al. 2022

Front. Public Health

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“…Although, Mab subsp. massiliense isolates contain a truncated erm (41) gene that has shown improved clinical treatment outcomes ( Bronson et al, 2021 ; Quang and Jang, 2021 ). Furthermore, CLA treatment induces the expression of transcriptional regulator WhiB7, which causes upregulation of erm (41) and eis 2 (which provides AMK resistance) ( Pryjma et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Although these outcomes that were from currently recommended regimens look atrocious, there is no viable alternative because of no potent anti- Mab candidates that were approved its efficacy in humans through clinical trials. In this perspective, it is clear that there is an urgent need for discovering and developing novel, more innovative anti- Mab drugs ( Quang and Jang, 2021 ). Therefore, there have been many attempts to find the best partner for CLA to improve treatment outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…It sometimes is used as a supplement to triple antibiotic therapy when current regimens are ineffective ( Singh et al, 2014 ; Pryjma et al, 2018 ; Kaushik et al, 2019 ; Kwon et al, 2019 ). However, TGC treatment has resulted in severe adverse effects, such as nausea and vomiting ( Chen et al, 2019 ; Quang and Jang, 2021 ). Thus, intravenous administration of TGC is not desirable for long-term treatment ( Kaushik et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

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Omadacycline Potentiates Clarithromycin Activity Against Mycobacterium abscessus

et al. 2021

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Mycobacterium abscessus is a difficult respiratory pathogen to treat, when compared to other nontuberculus mycobacteria (NTM), due to its drug resistance. In this study, we aimed to find a new clarithromycin partner that potentiated strong, positive, synergy against M. abscessus among current anti-M. abscessus drugs, including omadacycline, amikacin, rifabutin, bedaquiline, and cefoxitine. First, we determined the minimum inhibitory concentrations required of all the drugs tested for M. abscessus subsp. abscessus CIP104536T treatment using a resazurin microplate assay. Next, the best synergistic partner for clarithromycin against M. abscessus was determined using an in vitro checkerboard combination assay. Among the drug combinations evaluated, omadacycline showed the best synergistic effect with clarithromycin, with a fractional inhibitory concentration index of 0.4. This positive effect was also observed against M. abscessus clinical isolates and anti-M. abscessus drug resistant strains. Lastly, this combination was further validated using a M. abscessus infected zebrafish model. In this model, the clarithromycin-omadacyline regimen was found to inhibit the dissemination of M. abscessus, and it significantly extended the lifespan of the M. abscessus infected zebrafish. In summation, the synergy between two anti-M. abscessus compounds, clarithromycin and omadacycline, provides an attractive foundation for a new M. abscessus treatment regimen.

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“…Mycobacterium abscessus (Mab) has been recognised as a challenging respiratory pathogen among the non-tuberculous mycobacteria (NTM), often associated with poor outcomes of therapy and a high cost incurred due to prolonged therapy [1]. Although its acquisition was thought to occur through environmental exposure (e.g.…”

Section: Introductionmentioning

confidence: 99%

Structural-guided fragment-based drug discovery applied to antitoxin, MAB3862 opens a new possibility of exploring the Toxin and Antitoxin for antibiotics

Kim

Eun

Lee

et al. 2022

Preprint

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Mycobacterium abscessus (Mab) is a rapidly growing multidrug-resistant species among nontuberculous mycobacteria (NTM). Pulmonary infections caused by M. abscessus are difficult to treat and often result in an accelerated condition and premature death of immunosuppressed patients such as those with cystic fibrosis, putting them at a greater risk of other infections and increasing the urgency of developing a novel class of antibiotics. Here, we explore the use of toxin and antitoxin (TA) as an interesting and promising new class of target in a fragment-based drug-discovery approach. A de novo structure of Mab3862, an antitoxin of type 2 TA class in M. abscessus was elucidated and followed by drug discovery work. Very small molecules (fragments) are used to bind the antitoxin and then elaborated into drug-sized molecule that potentially trigger conformational change to prevent formation of toxin-antitoxin complex. Biophysical screening methods and binding-mode guidance from in silico docking were conducted. Grouping of fragments based on the binding site, creating a pharmacophore model, can facilitate further studies for rational design of inhibitors. Although targeting the TA complex for developing antibiotics is relatively novel and challenging, this could possibly open the gate for exploring it as potential drug target. Targeting one of the TA pairs might not be completely bactericidal. However, using this approach strategically with other antibiotics for synergic effect might be effective for patients with a persistence phenotype requiring prolonged therapy.

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Current Molecular Therapeutic Agents and Drug Candidates for Mycobacterium abscessus

Cited by 19 publications

References 171 publications

Case Report: Mycobacterium senegalense Infection After Cholecystectomy

Case Report: Mycobacterium senegalense Infection After Cholecystectomy

Omadacycline Potentiates Clarithromycin Activity Against Mycobacterium abscessus

Structural-guided fragment-based drug discovery applied to antitoxin, MAB3862 opens a new possibility of exploring the Toxin and Antitoxin for antibiotics

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