Nontuberculous Mycobacteria in Cystic Fibrosis

AbstractNontuberculous mycobacteria (NTM) can cause chronic pulmonary infection in susceptible hosts. Individuals with cystic fibrosis (CF), a multisystem disease predominated by progressive structural lung disease, are particularly vulnerable. Only recently have NTM been recognized for their potential to cause lung deterioration in CF patients. The reported prevalence varies widely from 4 to 40%, significantly more common than in the general population, but this varies because of multiple factors including inconsistent screening practices. Mycobacterium abscessus complex and Mycobacterium avium complex are the two most common species recovered. Defining NTM pulmonary disease in a CF patient can present challenges as it can be difficult to distinguish from the other potentially pathogenic organisms in the lung microbiome. In general, treatment regimens do not differ from the non-CF population but the clinician should be aware of potential interactions with other CF therapies. Recent population-level genomics has raised serious concern for indirect person-to-person transmission of several dominating NTM clones worldwide, raising awareness for increase prevention strategies when CF patients potentially congregate, such as clinic visits. Lung transplantation is controversial in those with NTM present in sputum culture but the available evidence suggests that this is not an absolute contraindication.

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

Microorganisms ◽

10.3390/microorganisms9081597 ◽

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.

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Current Opinions in the Treatment of Pulmonary Nontuberculous Mycobacteria in Non-Cystic Fibrosis Patients: Mycobacterium abscessus Group, Mycobacterium avium Complex, and Mycobacterium kansasii

Current Treatment Options in Infectious Diseases ◽

10.1007/s40506-014-0032-2 ◽

2014 ◽

Vol 6 (4) ◽

pp. 392-408 ◽

Cited By ~ 1

Author(s):

Barbara A. Brown-Elliott ◽

Julie V. Philley ◽

Jeana L. Benwill ◽

Richard J. Wallace

Keyword(s):

Cystic Fibrosis ◽

Mycobacterium Avium ◽

Mycobacterium Avium Complex ◽

Nontuberculous Mycobacteria ◽

Mycobacterium Abscessus ◽

Mycobacterium Kansasii

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Mycobacterium abscessus and Other Nontuberculous Mycobacteria: Evolving Respiratory Pathogens in Cystic Fibrosis: A Case Report and Review

Southern Medical Journal ◽

10.1097/01.smj.0000163311.70464.91 ◽

2005 ◽

Vol 98 (6) ◽

pp. 657-661 ◽

Cited By ~ 24

Author(s):

Don Hayes

Keyword(s):

Cystic Fibrosis ◽

Case Report ◽

Nontuberculous Mycobacteria ◽

Mycobacterium Abscessus ◽

Respiratory Pathogens

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Population Genomics of Nontuberculous Mycobacteria Recovered from United States Cystic Fibrosis Patients

10.1101/663559 ◽

2019 ◽

Cited By ~ 1

Author(s):

Nabeeh A. Hasan ◽

Rebecca M. Davidson ◽

L. Elaine Epperson ◽

Sara M. Kammlade ◽

Rachael R. Rodger ◽

...

Keyword(s):

United States ◽

Cystic Fibrosis ◽

Population Genomics ◽

Nontuberculous Mycobacteria ◽

Abundant Species ◽

The United States ◽

Mycobacterium Abscessus ◽

Genomic Diversity ◽

Nucleotide Polymorphisms ◽

Emerging Pathogens

AbstractNontuberculous mycobacteria (NTM) pose a threat to individuals with cystic fibrosis (CF) due to an increased prevalence of pulmonary infections, innate drug resistance of the bacteria, and potential transmission between CF patients. To explore the genetic diversity of NTM isolated from CF patients within the United States (US) and to identify potential transmission events, we sequenced and analyzed the genomes of 341 NTM isolates from 191 CF patients as part of a nationwide surveillance study. The most abundant species in the isolate cohort wereMycobacterium abscessus(59.5%), followed by species in theMycobacterium aviumcomplex (37.5%). Phylogenomic analyses of the threeM. abscessussubspecies revealed that more than half of CF patients had isolates in one of four dominant clones, including two dominant clones ofM. abscessussubspeciesabscessusand two dominant clones ofM. abscessussubspeciesmassiliense. M. aviumisolates from US CF patients, however, do not have dominant clones and are phylogenetically diverse. Longitudinal NTM isolates were compared to determine genome-wide single nucleotide polymorphisms (SNPs) that occur within patients over time. This information was used to compare between and within-patient SNP distributions, to quantitatively define SNP thresholds suggestive of transmission, and calculate a posterior probability of recent transmission given the SNP distance between two isolates from different patients. Out of 114 patients withM. abscessussubspecies, ten clusters of highly similar isolates from 26 patients were identified. Among the 26 patients in theM. abscessusclusters, 12 attended the same CF care centers. No highly similar isolate clusters were observed inM. avium. Our study reveals the contrasting genomic diversity and epidemiology of two major NTM taxa and the potential for between-patient exposure and cross-transmission of these emerging pathogens.

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Targeted Drug Delivery Technologies Potentiate the Overall Therapeutic Efficacy of an Indole Derivative in a Mouse Cystic Fibrosis Setting

Cells ◽

10.3390/cells10071601 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1601

Author(s):

Matteo Puccetti ◽

Marilena Pariano ◽

Giorgia Renga ◽

Ilaria Santarelli ◽

Fiorella D’Onofrio ◽

...

Keyword(s):

Cystic Fibrosis ◽

Targeted Drug Delivery ◽

Fungal Infections ◽

Murine Models ◽

Multisystem Disease ◽

Aryl Hydrocarbon ◽

Target Organs ◽

Infection And Inflammation ◽

Anti Inflammatory ◽

Inflammatory Toxicity

Inflammation plays a major role in the pathophysiology of cystic fibrosis (CF), a multisystem disease. Anti-inflammatory therapies are, therefore, of interest in CF, provided that the inhibition of inflammation does not compromise the ability to fight pathogens. Here, we assess whether indole-3-aldehyde (3-IAld), a ligand of the aryl hydrocarbon receptor (AhR), may encompass such an activity. We resorted to biopharmaceutical technologies in order to deliver 3-IAld directly into the lung, via dry powder inhalation, or into the gut, via enteric microparticles, in murine models of CF infection and inflammation. We found the site-specific delivery of 3-IAld to be an efficient strategy to restore immune and microbial homeostasis in CF organs, and mitigate lung and gut inflammatory pathology in response to fungal infections, in the relative absence of local and systemic inflammatory toxicity. Thus, enhanced delivery to target organs of AhR agonists, such as 3-IAld, may pave the way for the development of safe and effective anti-inflammatory agents in CF.

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Phosphorus stress induces the synthesis of novel glycolipids in Pseudomonas aeruginosa that confer protection against a last-resort antibiotic

The ISME Journal ◽

10.1038/s41396-021-01008-7 ◽

2021 ◽

Author(s):

Rebekah A. Jones ◽

Holly Shropshire ◽

Caimeng Zhao ◽

Andrew Murphy ◽

Ian Lidbury ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Antibiotic Sensitivity ◽

Polymyxin B ◽

Growth Conditions ◽

Membrane Lipid ◽

Comparative Genomic ◽

P Limitation ◽

Lung Microbiome ◽

Glycolipid Synthesis

AbstractPseudomonas aeruginosa is a nosocomial pathogen with a prevalence in immunocompromised individuals and is particularly abundant in the lung microbiome of cystic fibrosis patients. A clinically important adaptation for bacterial pathogens during infection is their ability to survive and proliferate under phosphorus-limited growth conditions. Here, we demonstrate that P. aeruginosa adapts to P-limitation by substituting membrane glycerophospholipids with sugar-containing glycolipids through a lipid renovation pathway involving a phospholipase and two glycosyltransferases. Combining bacterial genetics and multi-omics (proteomics, lipidomics and metatranscriptomic analyses), we show that the surrogate glycolipids monoglucosyldiacylglycerol and glucuronic acid-diacylglycerol are synthesised through the action of a new phospholipase (PA3219) and two glycosyltransferases (PA3218 and PA0842). Comparative genomic analyses revealed that this pathway is strictly conserved in all P. aeruginosa strains isolated from a range of clinical and environmental settings and actively expressed in the metatranscriptome of cystic fibrosis patients. Importantly, this phospholipid-to-glycolipid transition comes with significant ecophysiological consequence in terms of antibiotic sensitivity. Mutants defective in glycolipid synthesis survive poorly when challenged with polymyxin B, a last-resort antibiotic for treating multi-drug resistant P. aeruginosa. Thus, we demonstrate an intriguing link between adaptation to environmental stress (nutrient availability) and antibiotic resistance, mediated through membrane lipid renovation that is an important new facet in our understanding of the ecophysiology of this bacterium in the lung microbiome of cystic fibrosis patients.

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