scholarly journals Subspecies-specific sequence detection for differentiation of Mycobacterium abscessus complex

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alina Minias ◽  
Lidia Żukowska ◽  
Jakub Lach ◽  
Tomasz Jagielski ◽  
Dominik Strapagiel ◽  
...  
Keyword(s):  
Dna Hybridization ◽  
Mycobacterium Abscessus ◽  
Human Pathogens ◽  
Specific Sequence ◽  
Sequence Detection ◽  
Virtual Database ◽  
Mycobacterium Abscessus Complex ◽  
Etiologic Agents ◽  
Signature Sequences ◽  
Novel Method

Abstract Mycobacterium abscessus complex (MABC) is a taxonomic group of rapidly growing, nontuberculous mycobacteria that are found as etiologic agents of various types of infections. They are considered as emerging human pathogens. MABC consists of 3 subspecies—M. abscessus subsp. bolletti, M. abscessus subsp. massiliense and M. abscessus subsp. abscessus. Here we present a novel method for subspecies differentiation of M. abscessus named Subspecies-Specific Sequence Detection (SSSD). This method is based on the presence of signature sequences present within the genomes of each subspecies of MABC. We tested this method against a virtual database of 1505 genome sequences of MABC. Further, we detected signature sequences of MABC in 45 microbiological samples through DNA hybridization. SSSD showed high levels of sensitivity and specificity for differentiation of subspecies of MABC, comparable to those obtained by rpoB sequence typing.

scholarly journals Decontamination Strategies Used for AFB Culture Significantly Reduce the Viability of Mycobacterium abscessus Complex in Sputum Samples from Patients with Cystic Fibrosis

2021 ◽  
Vol 9 (8) ◽  
pp. 1597
Author(s):  
Dominic Stephenson ◽  
Audrey Perry ◽  
Andrew Nelson ◽  
Ali E. Robb ◽  
Matthew F. Thomas ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Oxalic Acid ◽  
Nontuberculous Mycobacteria ◽  
Optimal Recovery ◽  
Mycobacterium Abscessus ◽  
Colony Count ◽  
Respiratory Pathogens ◽  
Quantitative Culture ◽  
Mycobacterium Abscessus Complex ◽  
Oxalic Acids

Nontuberculous mycobacteria are important respiratory pathogens in patients with cystic fibrosis (CF). For diagnosis, international guidelines recommend culture of sputum that has been decontaminated via chemical treatment. Fifty-six sputum samples from 32 patients known to be previously colonized or infected with NTM were subdivided, and the aliquots were subjected to six different decontamination strategies, followed by quantitative culture for NTM. Thirty sputum samples contained Mycobacterium abscessus complex (MABSC) and 11 contained Mycobacterium avium complex (MAC). Decontamination strategies included treatment with N-acetyl L-cysteine with 2% sodium hydroxide (NALC-NaOH), 4% NaOH, 1% chlorhexidine, 0.5 N sulfuric acid, 5% oxalic acid, double decontamination with NALC-NaOH, followed by 5% oxalic acid, and saline (0.85%) as a control. The samples were also cultured directly with no treatment. Treatment with NALC-NaOH resulted in an average reduction in colony count of 87% for MABSC when compared with direct culture. NaOH at 4% caused a 98.3% average reduction in colony count. All treatments that included NaOH resulted in colony counts that were statistically lower than those obtained from direct culture or the saline-treated control (p < 0.05). Standard treatments using sulfuric or oxalic acids were less deleterious, but still resulted in an average reduction in colony count of at least 30%. The viability of MAC was much less affected by most decontamination treatments. In conclusion, the viability of MABSC was severely compromised by standard decontamination regimens. This supports recent evidence showing that optimal recovery of MABSC is achieved by culture on an appropriate selective agar without decontamination of sputum samples.

scholarly journals Evidence for Inhibition of Topoisomerase 1A by Gold(III) Macrocycles and Chelates TargetingMycobacterium tuberculosisandMycobacterium abscessus

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Rashmi Gupta ◽  
Carolina Rodrigues Felix ◽  
Matthew P. Akerman ◽  
Kate J. Akerman ◽  
Cathryn A. Slabber ◽  
...  
Keyword(s):  
Mycobacterium Abscessus ◽  
Cross Resistance ◽  
Human Pathogens ◽  
Intrinsic Resistance ◽  
Content Type ◽  
Starting Point ◽  
Scalable Synthesis ◽  
High Level ◽  
Novel Drug

ABSTRACTMycobacterium tuberculosisand the fast-growing speciesMycobacterium abscessusare two important human pathogens causing persistent pulmonary infections that are difficult to cure and require long treatment times. The emergence of drug-resistantM. tuberculosisstrains and the high level of intrinsic resistance ofM. abscessuscall for novel drug scaffolds that effectively target both pathogens. In this study, we evaluated the activity of bis(pyrrolide-imine) gold(III) macrocycles and chelates, originally designed as DNA intercalators capable of targeting human topoisomerase types I and II (Topo1 and Topo2), againstM. abscessusandM. tuberculosis. We identified a total of 5 noncytotoxic compounds active against both mycobacterial pathogens under replicatingin vitroconditions. We chose one of these hits, compound 14, for detailed analysis due to its potent bactericidal mode of inhibition and scalable synthesis. The clinical relevance of this compound was demonstrated by its ability to inhibit a panel of diverseM. tuberculosisandM. abscessusclinical isolates. Prompted by previous data suggesting that compound 14 may target topoisomerase/gyrase enzymes, we demonstrated that it lacked cross-resistance with fluoroquinolones, which target theM. tuberculosisgyrase.In vitroenzyme assays confirmed the potent activity of compound 14 against bacterial topoisomerase 1A (Topo1) enzymes but not gyrase. Novel scaffolds like compound 14 with potent, selective bactericidal activity againstM. tuberculosisandM. abscessusthat act on validated but underexploited targets like Topo1 represent a promising starting point for the development of novel therapeutics for infections by pathogenic mycobacteria.

scholarly journals Importance of Reciprocal Balance of T Cell Immunity in Mycobacterium abscessus Complex Lung Disease

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e109941 ◽  
Author(s):  
Su-Young Kim ◽  
Won-Jung Koh ◽  
Yee Hyung Kim ◽  
Byeong-Ho Jeong ◽  
Hye Yun Park ◽  
...  
Keyword(s):  
T Cell ◽  
Lung Disease ◽  
Mycobacterium Abscessus ◽  
T Cell Immunity ◽  
Mycobacterium Abscessus Complex ◽  
Cell Immunity

scholarly journals Novel Method to Detect a Construct-Specific Sequence of the Acetolactate Synthase Gene in Genetically-Modified Flax CDC Triffid (FP967)

2010 ◽  
Vol 33 (3) ◽  
pp. 532-534 ◽  
Author(s):  
Kosuke Nakamura ◽  
Hiroshi Akiyama ◽  
Chihiro Yamada ◽  
Rie Satoh ◽  
Daiki Makiyama ◽  
...  
Keyword(s):  
Genetically Modified ◽  
Acetolactate Synthase ◽  
Specific Sequence ◽  
Novel Method

scholarly journals 1350. Clofazimine as an Oral Companion Drug for Treatment of Mycobacterium abscessus complex Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S488-S489
Author(s):  
Joy Yong ◽  
Ka Lip Chew ◽  
Paul Tambyah
Keyword(s):  
Active Agent ◽  
Liver Function Tests ◽  
Mycobacterium Abscessus ◽  
Prolonged Treatment ◽  
Attractive Alternative ◽  
In Vitro Susceptibility ◽  
Treatment Regimens ◽  
Drug Intolerance ◽  
Mycobacterium Abscessus Complex

Abstract Background Infections caused by the multi-drug-resistant Mycobacterium abscessus complex (MabsC) are challenging to treat and often require multiple antimicrobials for a prolonged treatment course and still have poor outcomes. Clofazimine, an oral anti-leprosy drug, has demonstrated good in vitro susceptibility and is being increasingly employed in treatment regimens for MabsC infections. We performed a drug-use-evaluation of clofazimine in the treatment of MabsC infections. Methods A retrospective review was performed for all patients with MabsC infections treated with clofazimine-containing regimens from January 2014 to June 2017. Results Twenty-nine patients were included. Twelve patients had pulmonary MabsC infections and seventeen had extrapulmonary infections. All isolates had clofazimine minimum-inhibitory-concentration of ≤0.5 mg/L as tested by broth microdilution. Clofazimine was prescribed at initiation of therapy in 31.0% (9/29), as a companion drug during maintenance therapy after initial intravenous therapy in 44.8% (13/29) and as part of salvage therapy due to disease progression or drug intolerance in 24.1% (7/29) of patients. Dosing of clofazimine for the pediatric patients was prescribed at 1–2 mg/kg/day while the adult patients received a range of 50–200 mg/day. Clofazimine was given for a median duration of 148.5 days (range: 14–1212) and most commonly in combination with clarithromycin (82.8%), amikacin (58.6%), and cefoxitin (24.1%). Twelve patients had documented adverse reactions attributable to clofazimine: skin hyperpigmentation (66.7%), abnormal liver function tests (16.7%), and gastrointestinal disturbance (16.7%). Table 1 describes the patients who had clofazimine ceased due to an adverse effect. Nine patients with pulmonary MabsC infections and 16 with extrapulmonary MabsC infections had documented improvement in symptoms. Conclusion Clofazimine as a companion drug in the treatment of MabsC infections was reasonably tolerated over a prolonged period of time. Its availability as an oral active agent makes it an attractive alternative to IV companion drugs and potentially improves compliance to the protracted treatment courses for patients with MabsC infections. Disclosures All authors: No reported disclosures.

scholarly journals Clinical aspects of the Mycobacterium abscessus complex

2018 ◽  
Vol 44 (5) ◽  
pp. 434-435
Author(s):  
Beuy Joob ◽  
Viroj Wiwanitkit ◽  
José Tadeu Colares Monteiro
Keyword(s):  
Mycobacterium Abscessus ◽  
Clinical Aspects ◽  
Mycobacterium Abscessus Complex
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