Non-Tuberculous Mycobacteria multispecies biofilms in cystic fibrosis: development of an in vitro Mycobacterium abscessus and Pseudomonas aeruginosa dual species biofilm model

Rodríguez-Sevilla, Graciela; García-Coca, Marta; Romera-García, David; Aguilera-Correa, John Jairo; Mahíllo‐Fernández, Ignacio; Esteban, Jaime; Pérez‐Jorge, Concepción

doi:10.1016/j.ijmm.2018.03.003

Cited by 23 publications

(31 citation statements)

References 44 publications

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“…MAB disease progression shares some aspects with M. tuberculosis and, as the disease evolves, this pathogen also lives inside granulomas or pulmonary nodules that are characterized with the low oxygen tension (anaerobic conditions) [37]. Furthermore, MAB has an ability to form biofilm on the surface of the airways inside of the human lung [38]. Due to the fact that the drug activity is generally established against aerobically growing and metabolically active bacteria, when the same antimicrobials are used against bacteria of different phenotypes, treatment outcomes vary, and many times they are ineffective.…”

Section: Discussionmentioning

confidence: 99%

Exposure of Mycobacterium abscessus to Environmental Stress and Clinically Used Antibiotics Reveals Common Proteome Response among Pathogenic Mycobacteria

et al. 2020

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Mycobacterium abscessus subsp. abscessus (MAB) is a clinically important nontuberculous mycobacterium (NTM) causing pulmonary infection in patients such as cystic fibrosis and bronchiectasis. MAB is naturally resistant to the majority of available antibiotics. In attempts to identify the fundamental response of MAB to aerobic, anaerobic, and biofilm conditions (as it is encountered in patients) and during exposure to antibiotics, we studied bacterial proteome using tandem mass tag mass spectrometry sequencing. Numerous de novo synthesized proteins belonging to diverse metabolic pathways were found in anaerobic and biofilm conditions, including glycolysis/gluconeogenesis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation, nitrogen metabolism, and glyoxylate and dicarboxylate metabolism. Upon exposure to amikacin and linezolid under stress environments, MAB displayed metabolic enrichment for glycerophospholipid metabolism and oxidative phosphorylation. By comparing proteomes of two significant NTMs, MAB and M. avium subsp. hominissuis, we found highly synthesized shared enzymes of oxidative phosphorylation, TCA cycle, glycolysis/gluconeogenesis, glyoxylate/dicarboxylate, nitrogen metabolism, peptidoglycan biosynthesis, and glycerophospholipid/glycerolipid metabolism. The activation of peptidoglycan and fatty acid biosynthesis pathways indicates the attempt of bacteria to modify the cell wall, influencing the susceptibility to antibiotics. This study establishes global changes in the synthesis of enzymes promoting the metabolic shift and enhancing the pathogen resistance to antibiotics within different environments.

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Section: Discussionmentioning

confidence: 99%

Exposure of Mycobacterium abscessus to Environmental Stress and Clinically Used Antibiotics Reveals Common Proteome Response among Pathogenic Mycobacteria

et al. 2020

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“…The dual species biofilms in which Pa grew a "blanketed" biofilm over NTM demonstrated increased antibiotic resistance in this study-it is plausible that this structure (Fig. 1) could also protect NTM from pathogen surveillance techniques such as bronchoalveolar lavage (BAL) and contribute to its underdetection (6). (6).…”

Section: Potential For Interactions In a Polymicrobial Communitymentioning

confidence: 80%

“…Pa is fast growing and motile, while NTM is relatively slow growing and non-motile. This could give Pa an advantage that allows it to outcompete NTM; however, these results suggest that Pa does not or cannot directly inhibit NTM (6). When considering whether this interaction occurs in vivo in the CF lungs, it would not only have important implications for treatment efficacy but also pathogen surveillance.…”

Section: Potential For Interactions In a Polymicrobial Communitymentioning

confidence: 97%

“…While compiling this minireview, we found very few published studies that detail the interactions between Pa and NTM, although many experts agree that coinfections with these organisms are associated with negative patient outcomes both in CF and non-CF populations (20,45). Rodriguez-Sevilla et al (6) explored the mechanisms of interactions between Pa and NTM, demonstrating that clinical isolates of Pa and NTM (M. abscessus) are able to coexist in a dual species biofilm in vitro, where they form a "layered" or "blanketed" structure in which the Pa biofilm grows on top of the NTM biofilm (Fig. 1).…”

Section: Potential For Interactions In a Polymicrobial Communitymentioning

confidence: 99%

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Same Game, Different Players: Emerging Pathogens of the CF Lung

Gannon

Darch

2021

mBio

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The survival rates of individuals with cystic fibrosis (CF) have significantly increased as a result of improved therapies, such as the inclusion of cystic fibrosis transmembrane conductance regulator (CFTR) modulators for some mutations. However, microbial infection of the airways remains a significant clinical problem. The well-known pathogens Pseudomonas aeruginosa and Staphylococcus aureus continue to establish difficult-to-treat infections in the CF lung. However, in recent years, there has been an increased prevalence of both Aspergillus fumigatus (Af) and non-tuberculous mycobacteria (NTM) species isolated from CF patient sputa. The emergence of these pathogens opens an important area of discussion about multikingdom infections, specifically, how interspecies interactions have the potential to shape the course of infection, such as tolerance to host immune defenses and antimicrobial therapies. Their ability to establish themselves in an existing polymicrobial environment suggests to us that microbial interactions play a significant role, and characterizing these mechanisms and understanding their implications will be critical to the future development of better antimicrobial therapies. With this minireview, we hope to inspire conversations about and demonstrate the merit of more research in this area. IMPORTANCE Incidences of non-tuberculous mycobacteria (NTM) and Aspergillus fumigatus have increased around the world over the past decade and have become a significant health threat to immunocompromised individuals such as those with cystic fibrosis (CF). CF is characterized by the buildup of mucus in the lungs which become chronically infected by a myriad of pathogens. The emergence of these pathogens in established infection sites raises many questions about the microbial ecosystems they become a part of, specifically how changes in these ecosystems impact disease outcomes. Understanding how microbial communities establish and maintain themselves despite medical treatment and host immune defenses will be critical for the development of improved therapeutic strategies.

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“…Therefore, tolerance and not resistance might be involved in this mechanism (26). The increased tolerance might be a result of the sum of different mechanisms, such as failure of the antibiotics to penetrate the biofilm due to the different composition of the biofilm matrix in single-versus dual-species biofilms (27)(28)(29)(30)(31) or suppression of aminoglycoside activity due to low pH and oxygen tension in the inner zone of the biofilm (32,33), where M. abscessus was previously shown to reside (21). This altered susceptibility to amikacin in single-versus dual-species biofilms could not be observed in our previous study, in which amikacin efficacy in inhibiting biofilm formation was tested for 6 h (14).…”

mentioning

confidence: 99%

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

Rodríguez-Sevilla

Crabbé

García-Coca

et al. 2019

Antimicrob Agents Chemother

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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.

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Non-Tuberculous Mycobacteria multispecies biofilms in cystic fibrosis: development of an in vitro Mycobacterium abscessus and Pseudomonas aeruginosa dual species biofilm model

Cited by 23 publications

References 44 publications

Exposure of Mycobacterium abscessus to Environmental Stress and Clinically Used Antibiotics Reveals Common Proteome Response among Pathogenic Mycobacteria

Exposure of Mycobacterium abscessus to Environmental Stress and Clinically Used Antibiotics Reveals Common Proteome Response among Pathogenic Mycobacteria

Same Game, Different Players: Emerging Pathogens of the CF Lung

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

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