scholarly journals 417: Identifying the mechanisms of regulation of biofilm formation in Mycobacterium abscessus: A CF clinical pathogen

2021 ◽  
Vol 20 ◽  
pp. S196
Author(s):  
M. Meyer ◽  
W. DePas
Keyword(s):  
Biofilm Formation ◽  
Mycobacterium Abscessus

Environment in the lung of cystic fibrosis patients stimulates the expression of biofilm phenotype in Mycobacterium abscessus

2022 ◽  
Vol 71 (1) ◽  
Author(s):  
Bailey F. Keefe ◽  
Luiz E. Bermudez
Keyword(s):  
Cystic Fibrosis ◽  
Host Cell ◽  
Biofilm Formation ◽  
Type Species ◽  
Divalent Cations ◽  
Mycobacterium Abscessus ◽  
Content Type ◽  
Link Type ◽  
Populations At Risk

Introduction. Pulmonary infections caused by organisms of the Mycobacterium abscessus complex are increasingly prevalent in populations at risk, such as patients with cystic fibrosis, bronchiectasis and emphysema. Hypothesis. M. abscessus infection of the lung is not observed in immunocompetent individuals, which raises the possibility that the compromised lung environment is a suitable niche for the pathogen to thrive in due to the overproduction of mucus and high amounts of host cell lysis. Aim. Evaluate the ability of M. abscessus to form biofilm and grow utilizing in vitro conditions as seen in immunocompromised lungs of patients. Methodology. We compared biofilm formation and protein composition in the presence and absence of synthetic cystic fibrosis medium (SCFM) and evaluated the bacterial growth when exposed to human DNA. Results. M. abscessus is capable of forming biofilm in SCFM. By eliminating single components found in the medium, it became clear that magnesium works as a signal for the biofilm formation, and chelation of the divalent cations resulted in the suppression of biofilm formation. Investigation of the specific proteins expressed in the presence of SCFM and in the presence of SCFM lacking magnesium revealed many different proteins between the conditions. M. abscessus also exhibited growth in SCFM and in the presence of host cell DNA, although the mechanism of DNA utilization remains unclear. Conclusions. In vitro conditions mimicking the airways of patients with cystic fibrosis appear to facilitate M. abscessus establishment of infection, and elimination of magnesium from the environment may affect the ability of the pathogen to establish infection.

scholarly journals Mycobacterium abscessus Smooth and Rough Morphotypes Form Antimicrobial-Tolerant Biofilm Phenotypes but Are Killed by Acetic Acid

2018 ◽  
Vol 62 (3) ◽  
Author(s):  
Gillian Clary ◽  
Smitha J. Sasindran ◽  
Nathan Nesbitt ◽  
Laurel Mason ◽  
Sara Cole ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Intracellular Survival ◽  
Mycobacterium Abscessus ◽  
Human Macrophage ◽  
Content Type ◽  
Prevailing Paradigm ◽  
Chronic Pulmonary Diseases ◽  
The Face

ABSTRACT Mycobacterium abscessus has emerged as an important pathogen in people with chronic inflammatory lung diseases such as cystic fibrosis, and recent reports suggest that it may be transmissible by fomites. M. abscessus exhibits two major colony morphology variants: a smooth morphotype ( Ma Sm ) and a rough morphotype ( Ma Rg ). Biofilm formation, prolonged intracellular survival, and colony variant diversity can each contribute to the persistence of M. abscessus and other bacterial pathogens in chronic pulmonary diseases. A prevailing paradigm of chronic M. abscessus infection is that Ma Sm is a noninvasive, biofilm-forming, persistent phenotype and Ma Rg an invasive phenotype that is unable to form biofilms. We show that Ma Rg is hyperaggregative and forms biofilm-like aggregates, which, like Ma Sm biofilm aggregates, are significantly more tolerant than planktonic variants to acidic pHs, hydrogen peroxide (H 2 O 2 ), and treatment with amikacin or azithromycin. We further show that both variants are recalcitrant to antibiotic treatment inside human macrophage-like cells and that Ma Rg is more refractory than Ma Sm to azithromycin. Our results indicate that biofilm-like aggregation and protracted intracellular survival may each contribute to the persistence of this problematic pathogen in the face of antimicrobial agents regardless of morphotype. Biofilms of each M. abscessus variant are rapidly killed, however, by acetic acid, which may help to prevent local fomite transmission.

scholarly journals Effect of Coptis chinensis on Biofilm Formation and Antibiotic Susceptibility in Mycobacterium abscessus

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Cheng-Yin Tseng ◽  
Mao-Feng Sun ◽  
Tsai-Chung Li ◽  
Ching-Ting Lin
Keyword(s):  
Antibiotic Susceptibility ◽  
Biofilm Formation ◽  
Inhibitory Concentration ◽  
Viral Infections ◽  
Treatment Options ◽  
Mycobacterium Abscessus ◽  
Minimal Bactericidal Concentration ◽  
Coptis Chinensis ◽  
Resistance Level ◽  
Main Compound

Mycobacterium abscessus infections are notoriously difficult to be treated and newer treatment options are required. Coptis chinensis (C. chinensis) and its main compound berberine are frequently used to treat bacterial and viral infections. In this study, the susceptibility of M. abscessus to C. chinensis extract and berberine was assessed by minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) evaluation. The effects of C. chinensis and berberine on biofilm formation and antibiotic susceptibility in M. abscessus were observed. C. chinensis at concentrations of MIC (1.5 mg/mL) and 2 × MIC (3.0 mg/mL) and berberine at ½ × MIC (0.125 mg/mL) demonstrated a strong inhibition of biofilm formation. Concentration of C. chinensis at ½ × MIC resulted in a significant reduction in MICs of trimethoprim/sulfamethoxazole (TMP/SXT), clarithromycin (CLA), and linezolid (LZD). Similarly, ½ × MIC berberine had a significant effect on the MIC reductions of nine antibiotics including TMP/SXT, CLA, and LZD. Notably, the resistance level MIC of LZD against M. abscessus was reversed to a susceptible level by treatment with either C. chinensis or berberine. Therefore, C. chinensis and berberine have the potential to produce a synergistic antimycobacterial effect, reduce biofilm formation, and decrease antibacterial resistance to LZD in M. abscessus.

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 Biofilm-associatedMycobacterium abscessuscells have altered antibiotic tolerance and surface glycolipids in Artificial Cystic Fibrosis Sputum Media

2018 ◽  
Author(s):  
Augusto Cesar Hunt-Serracin ◽  
Brian J. Parks ◽  
Joseph Boll ◽  
Cara Boutte
Keyword(s):  
Cystic Fibrosis ◽  
Biofilm Formation ◽  
Mycobacterium Abscessus ◽  
Cell Physiology ◽  
Antibiotic Tolerance ◽  
Planktonic Cells ◽  
Cystic Fibrosis Sputum ◽  
Trehalose Dimycolate ◽  
Poor Treatment ◽  
Nutrient Conditions

AbstractMycobacterium abscessus(Mab) is a biofilm-forming, multi-drug resistant, non-tuberculous mycobacterial (NTM) pathogen increasingly found in Cystic Fibrosis patients. Antibiotic treatment for these infections is often unsuccessful, partly due toMab’s high intrinsic antibiotic resistance. It is not clear whether antibiotic tolerance caused by biofilm formation also contributes to poor treatment outcomes. We studied the surface glycolipids and antibiotic tolerance ofMabbiofilms grown in Artificial Cystic Fibrosis Sputum (ACFS) media in order to determine how they are affected by nutrient conditions that mimic infection. We found thatMabdisplays more of the virulence lipid trehalose dimycolate when grown in ACFS compared to standard lab media. In ACFS media, biofilm-associated cells are more antibiotic tolerant than planktonic cells in the same well. This contrasts with standard lab medias, where biofilm and planktonic cells are both highly antibiotic tolerant. These results indicate thatMabcell physiology in biofilms depends on environmental factors, and that nutrient conditions found within Cystic Fibrosis infections could contribute to both increased virulence and antibiotic tolerance.

scholarly journals Antimicrobial Treatment Provides a Competitive Advantage to Mycobacterium abscessus in a Dual-Species Biofilm with Pseudomonas aeruginosa

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Graciela Rodríguez-Sevilla ◽  
Aurélie Crabbé ◽  
Marta García-Coca ◽  
John Jairo Aguilera-Correa ◽  
Jaime Esteban ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Therapy ◽  
Biofilm Formation ◽  
Mycobacterium Abscessus ◽  
Antimicrobial Treatment ◽  
Physiological Factors ◽  
Content Type ◽  
Lung Infections ◽  
The Ideal

ABSTRACT The physiological factors that contribute to Mycobacterium abscessus lung infections remain unclear. We determined whether antibiotic treatment targeting a major cystic fibrosis pathogen (i.e., Pseudomonas aeruginosa) could provide the ideal conditions for the establishment of M. abscessus infection. Our data showed that P. aeruginosa inhibited M. abscessus biofilm formation under control conditions and that antimicrobial therapy selectively targeting P. aeruginosa diminished this competitive interaction, thereby increasing M. abscessus survival.

scholarly journals Spontaneous reversion of Mycobacterium abscessus from a smooth to a rough morphotype is associated with reduced expression of glycopeptidolipid and reacquisition of an invasive phenotype

Microbiology ◽  
2006 ◽  
Vol 152 (6) ◽  
pp. 1581-1590 ◽  
Author(s):  
Susan T. Howard ◽  
Elizabeth Rhoades ◽  
Judith Recht ◽  
Xiuhua Pang ◽  
Anny Alsup ◽  
...  
Keyword(s):  
Cell Wall ◽  
Biofilm Formation ◽  
Marked Reduction ◽  
Serial Passage ◽  
Mycobacterium Abscessus ◽  
Invasive Infection ◽  
Virulence Determinants ◽  
Wild Type ◽  
Isogenic Mutant ◽  
Spontaneous Reversion

Mycobacterium abscessus is an increasingly important cause of human disease; however, virulence determinants are largely uncharacterized. Previously, it was demonstrated that a rough, wild-type human clinical isolate (390R) causes persistent, invasive infection, while a smooth isogenic mutant (390S) has lost this capability. During serial passage of 390S, a spontaneous rough revertant was obtained, which was named 390V. This revertant regained the ability to cause persistent, invasive infection in human monocytes and the lungs of mice. Glycopeptidolipid (GPL), which plays a role in environmental colonization, was present in abundance in the cell wall of 390S, and was associated with sliding motility and biofilm formation. In contrast, a marked reduction in the amount of GPL in the cell wall of 390R and 390V was correlated with cord formation, a property associated with mycobacterial virulence. These results indicate that the ability to switch between smooth and rough morphologies may allow M. abscessus to transition between a colonizing phenotype and a more virulent, invasive form.

scholarly journals Unique Features of Mycobacterium abscessus Biofilms Formed in Synthetic Cystic Fibrosis Medium

2021 ◽  
Vol 12 ◽  
Author(s):  
Juan M. Belardinelli ◽  
Wei Li ◽  
Charlotte Avanzi ◽  
Shiva K. Angala ◽  
Elena Lian ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Biofilm Formation ◽  
Therapeutic Strategies ◽  
Mycobacterium Abscessus ◽  
Extracellular Dna ◽  
Environmental Cues ◽  
Standard Laboratory ◽  
Mycolic Acids ◽  
Molecular Determinants ◽  
Biofilm Development

Characterizing Mycobacterium abscessus complex (MABSC) biofilms under host-relevant conditions is essential to the design of informed therapeutic strategies targeted to this persistent, drug-tolerant, population of extracellular bacilli. Using synthetic cystic fibrosis medium (SCFM) which we previously reported to closely mimic the conditions encountered by MABSC in actual cystic fibrosis (CF) sputum and a new model of biofilm formation, we show that MABSC biofilms formed under these conditions are substantially different from previously reported biofilms grown in standard laboratory media in terms of their composition, gene expression profile and stress response. Extracellular DNA (eDNA), mannose-and glucose-containing glycans and phospholipids, rather than proteins and mycolic acids, were revealed as key extracellular matrix (ECM) constituents holding clusters of bacilli together. None of the environmental cues previously reported to impact biofilm development had any significant effect on SCFM-grown biofilms, most likely reflecting the fact that SCFM is a nutrient-rich environment in which MABSC finds a variety of ways of coping with stresses. Finally, molecular determinants were identified that may represent attractive new targets for the development of adjunct therapeutics targeting MABSC biofilms in persons with CF.

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