scholarly journals Considerations for Phage Therapy Against Mycobacterium abscessus

2021 ◽  
Vol 11 ◽  
Author(s):  
Abrar Senhaji-Kacha ◽  
Jaime Esteban ◽  
Meritxell Garcia-Quintanilla
Keyword(s):  
Cystic Fibrosis ◽  
Neutralizing Antibodies ◽  
Phage Therapy ◽  
Opportunistic Pathogen ◽  
Mycobacterium Abscessus ◽  
Pulmonary Infections ◽  
Compassionate Use ◽  
Bacterial Genomes ◽  
Combined Use ◽  
Prolonged Effect

There is a global increasing number of Mycobacterium abscessus infections, especially pulmonary infections. Reduced therapeutic options exist against this opportunistic pathogen due to its high intrinsic and acquired levels of antibiotic resistance. Phage therapy is a promising afresh therapy, which uses viruses to lyse bacteria responsible for the infection. Bacteriophages have been recently administered under compassionate use to a 15-year-old patient infected with M. abscessus in combination with antibiotics with excellent results. This mini review highlights different recommendations for future phage administrations such as where to look for new phages, the use of cocktail of mycobacteriophages to broaden phage specificity and to tackle resistance and phage insensitivity due to temperate phages present in bacterial genomes, the combined use of phages and antibiotics to obtain a synergistic effect, the liposomal administration to reach a prolonged effect, intracellular delivery and protection against neutralizing antibodies, and the convenience of using this strategy in patients suffering from cystic fibrosis (CF) since phages are believed to promote immunomodulatory actions and eliminate biofilms.

scholarly journals Mycobacterium abscessus biofilms have viscoelastic properties which may contribute to their recalcitrance in chronic pulmonary infections

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Erin S. Gloag ◽  
Daniel J. Wozniak ◽  
Paul Stoodley ◽  
Luanne Hall-Stoodley
Keyword(s):  
Mechanical Properties ◽  
Cystic Fibrosis ◽  
Cell Wall ◽  
Biofilm Formation ◽  
Viscoelastic Properties ◽  
Normal Force ◽  
Mycobacterium Abscessus ◽  
Pulmonary Infections ◽  
Shear Forces

AbstractMycobacterium abscessus is emerging as a cause of recalcitrant chronic pulmonary infections, particularly in people with cystic fibrosis (CF). Biofilm formation has been implicated in the pathology of this organism, however the role of biofilm formation in infection is unclear. Two colony-variants of M. abscessus are routinely isolated from CF samples, smooth (MaSm) and rough (MaRg). These two variants display distinct colony morphologies due to the presence (MaSm) or absence (MaRg) of cell wall glycopeptidolipids (GPLs). We hypothesized that MaSm and MaRg variant biofilms might have different mechanical properties. To test this hypothesis, we performed uniaxial mechanical indentation, and shear rheometry on MaSm and MaRg colony-biofilms. We identified that MaRg biofilms were significantly stiffer than MaSm under a normal force, while MaSm biofilms were more pliant compared to MaRg, under both normal and shear forces. Furthermore, using theoretical indices of mucociliary and cough clearance, we identified that M. abscessus biofilms may be more resistant to mechanical forms of clearance from the lung, compared to another common pulmonary pathogen, Pseudomonas aeruginosa. Thus, the mechanical properties of M. abscessus biofilms may contribute to the persistent nature of pulmonary infections caused by this organism.

scholarly journals Genome Sequence of Pseudomonas aeruginosa Strain DK1-NH57388A, a Stable Mucoid Cystic Fibrosis Isolate

2016 ◽  
Vol 4 (1) ◽  
Author(s):  
Anders Norman ◽  
Oana Ciofu ◽  
Cristina Isabel Amador ◽  
Niels Høiby ◽  
Lars Jelsbak
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Animal Model ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Opportunistic Pathogen ◽  
Pulmonary Infections ◽  
Cystic Fibrosis Isolate ◽  
Lung Infections

Pseudomonas aeruginosa is an important opportunistic pathogen associated with chronic pulmonary infections and mortality in cystic fibrosis (CF) patients. Here, we present the complete genome sequence of stable mucoid P. aeruginosa strain DK1-NH57388A, a CF isolate which has previously been used to establish chronic lung infections in an animal model.

scholarly journals 482: Nebulized phage therapy for chronic Pseudomonas aeruginosa pulmonary infections in cystic fibrosis patients

2021 ◽  
Vol 20 ◽  
pp. S228
Author(s):  
M. Kahan-Hanum ◽  
S. Kredo-Russo ◽  
R. Edgar ◽  
L. Zelcbuch ◽  
I. Sherman ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Phage Therapy ◽  
Pulmonary Infections

scholarly journals Mycobacterium abscessus biofilms have viscoelastic properties which may contribute to their recalcitrance in chronic pulmonary infections

2020 ◽  
Author(s):  
Erin S. Gloag ◽  
Daniel J. Wozniak ◽  
Paul Stoodley ◽  
Luanne Hall-Stoodley
Keyword(s):  
Mechanical Properties ◽  
Cystic Fibrosis ◽  
Cell Wall ◽  
Biofilm Formation ◽  
Viscoelastic Properties ◽  
Normal Force ◽  
Mycobacterium Abscessus ◽  
Pulmonary Infections ◽  
Shear Forces

AbstractMycobacterium abscessus is emerging as a cause of recalcitrant chronic pulmonary infections, particularly in people with cystic fibrosis (CF). Biofilm formation has been implicated in the pathology of this organism, however the role of biofilm formation in infection is unclear. Two colony-variants of M. abscessus are routinely isolated from CF samples, smooth (MaSm) and rough (MaRg). These two variants display distinct colony morphologies due to the presence (MaSm) or absence (MaRg) of cell wall glycopeptidolipids (GPLs). We hypothesized that MaSm and MaRg variant biofilms might have different biophysical and mechanical properties, including stiffness, viscosity and elasticity. To test this hypothesis, we performed uniaxial mechanical indentation, and shear rheometry on MaSm and MaRg colony-biofilms. We identified that MaRg biofilms were significantly stiffer than MaSm under a normal force, while MaSm biofilms were more pliant compared to MaRg, under both normal and shear forces. Furthermore, using theoretical indices of mucociliary and cough clearence, we identified that M. abscessus biofilms may be more resistant to mechanical forms of clearance from the lung, compared to other common pulmonary pathogens, such as P. aeruginosa. Thus, the mechanical properties of M. abscessus biofilms may contribute to the persistent nature of pulmonary infections caused by this organism.

Cystic fibrosis. Biofilms involved in pulmonary infections

2013 ◽  
Vol 4 (2) ◽  
pp. 99-104
Author(s):  
Beata Sadowska ◽  
Marzena Więckowska-Szakiel ◽  
Małgorzata Paszkiewicz ◽  
Barbara Różalska
Keyword(s):  
Cystic Fibrosis ◽  
Pulmonary Infections

scholarly journals 1615. Isolation of Lytic Bacteriophages with Broad Host Range Activity Against Pseudomonas aeruginosa Strains Isolated from Respiratory Samples from Cystic Fibrosis Patients Intended for Therapeutic Application

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S801-S801
Author(s):  
Jose Alexander ◽  
Daniel Navas ◽  
Marly Flowers ◽  
Angela Charles ◽  
Amy Carr
Keyword(s):  
Cystic Fibrosis ◽  
Host Range ◽  
Phage Therapy ◽  
Clinical Isolates ◽  
Clinical Samples ◽  
Plaque Morphology ◽  
Broad Host Range ◽  
Chronic Infections ◽  
Clinically Significant ◽  
Host Target

Abstract Background With the rise of the antimicrobial resistance between different genera and species of bacteria, Phage Therapy is becoming a more realistic and accessible option for patients with limited or no antimicrobial options. Being able to have rapid access to a collection of clinical active phages is key for rapid implementation of phage therapy. The Microbiology Department at AdventHealth Orlando is performing routine screening of environmental and patient samples for isolation of phages against non-fermenting Gram negative bacteria to develop a Phage Bank. Methods Protocols for phage isolation from environmental sources such as lakes, rivers and sewers and clinical samples were developed. A series of respiratory, throat, stool and urine samples were processed following an internal protocol that includes centrifugation, filtration and enrichment. Clinical samples were centrifugated for 10 minutes, filtered using 0.45µm centrifugation filters, seeded with targeted host bacteria (clinical isolates) and incubated at 35°C for 24 hours. The enriched samples were centrifugated and filtered for a final phage enriched solution. Screening and isolation were performed using the Gracia method over trypticase soybean agar (TSA) for plaque morphology and quantification. Host range screening of other clinical isolates of P. aeruginosa was performed using the new isolated and purified phages. Results 4 lytic phages against clinical strains of P. aeruginosa from patient with diagnosis of cystic fibrosis (CF), were isolated and purified from 4 different respiratory samples, including sputum and bronchial alveolar lavage. All phages showed phenotypical characteristics of lytic activity. 1 phage was active against 4 strains of P. aeruginosa, 1 phage was active against 2 strains of P. aeruginosa and the remaining 2 phages were active only against the initial host target strain. Conclusion With this study we demonstrated the potential use of clinical samples as source for isolating active bacteriophages against clinically significant bacteria strains. Clinical samples from vulnerable population of patients with chronic infections are part of our routine “phage-hunting” process to stock and grow our Phage Bank project for future clinical use. Disclosures All Authors: No reported disclosures

scholarly journals Mab_3083c Is a Homologue of RNase J and Plays a Role in Colony Morphotype, Aggregation, and Sliding Motility of Mycobacterium abscessus

2021 ◽  
Vol 9 (4) ◽  
pp. 676
Author(s):  
Ting-Yu Liu ◽  
Sheng-Hui Tsai ◽  
Jenn-Wei Chen ◽  
Yu-Ching Wang ◽  
Shiau-Ting Hu ◽  
...  
Keyword(s):  
Type Strain ◽  
Wild Type Strain ◽  
Opportunistic Pathogen ◽  
Mycobacterium Abscessus ◽  
Colony Morphology ◽  
Clinical Strain ◽  
Immunocompromised Patients ◽  
Clinical Infection ◽  
Wild Type ◽  
Sliding Motility

Mycobacterium abscessus is an opportunistic pathogen causing human diseases, especially in immunocompromised patients. M. abscessus strains with a rough morphotype are more virulent than those with a smooth morphotype. Morphotype switch may occur during a clinical infection. To investigate the genes involved in colony morphotype switching, we performed transposon mutagenesis in a rough clinical strain of M. abscessus. A morphotype switching mutant (smooth) named mab_3083c::Tn was obtained. This mutant was found to have a lower aggregative ability and a higher sliding motility than the wild type strain. However, its glycopeptidolipid (GPL) content remained the same as those of the wild type. Complementation of the mutant with a functional mab_3083c gene reverted its morphotype back to rough, indicating that mab_3083c is associated with colony morphology of M. abscessus. Bioinformatic analyses showed that mab_3083c has a 75.4% identity in amino acid sequence with the well-characterized ribonuclease J (RNase J) of M. smegmatis (RNase JMsmeg). Complementation of the mutant with the RNase J gene of M. smegmatis also switched its colony morphology from smooth back to rough. These results suggest that Mab_3083c is a homologue of RNase J and involved in regulating M. abscessus colony morphotype switching.

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.

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