Prevotella melaninogenica, a Sentinel Species of Antibiotic Resistance in Cystic Fibrosis Respiratory Niche?

Lamoureux, Claudie; Guilloux, Charles-Antoine; Courteboeuf, Elise; Gouriou, S.; Héry-Arnaud, Geneviève

doi:10.3390/microorganisms9061275

Cited by 9 publications

(7 citation statements)

References 49 publications

(66 reference statements)

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“…In contrast, harmful associations have been observed including increased anaerobe abundance correlating to PEx occurrence [ 3 , 30–33 , 48 ]. Anaerobes have also been identified as carriers of antibiotic resistance genes relevant to therapeutics commonly employed in CF [ 49 , 50 ] including genes encoding several β-lactamases which may impart protection to neighboring organisms [ 44 , 50 , 51 ] ( Figure 3 ). Finally, anaerobic metabolism facilitates the production of several pro-inflammatory short-chain fatty acids (SCFAs) that may further amplify host immune responses [ 52 ].…”

Section: Who Are the Microbial Players?mentioning

confidence: 99%

Exploring the Cystic Fibrosis Lung Microbiome: Making the Most of a Sticky Situation

Thornton

Acosta

Surette

et al. 2022

Journal of the Pediatric Infectious Diseases Society

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Chronic lower respiratory tract infections are a leading contributor to morbidity and mortality in persons with cystic fibrosis (pwCF). Traditional respiratory tract surveillance culturing has focused on a limited range of classic pathogens; however, comprehensive culture and culture-independent molecular approaches have demonstrated complex communities highly unique to each individual. Microbial community structure evolves through the lifetime of pwCF and is associated with baseline disease state and rates of disease progression including occurrence of pulmonary exacerbations. While molecular analysis of the airway microbiome has provided insight into these dynamics, challenges remain including discerning not only “who is there” but “what they are doing” in relation to disease progression. Moreover, the microbiome can be leveraged as a multi-modal biomarker for both disease activity and prognostication. In this article, we review our evolving understanding of the role these communities play in pwCF and identify challenges in translating microbiome data to clinical practice.

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Section: Who Are the Microbial Players?mentioning

confidence: 99%

Exploring the Cystic Fibrosis Lung Microbiome: Making the Most of a Sticky Situation

Thornton

Acosta

Surette

et al. 2022

Journal of the Pediatric Infectious Diseases Society

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“…and Prevotella spp. are important in shaping health outcomes in pwCF based on studies using culture-dependent and -independent approaches (30,(33)(34)(35)(36)(37)(38)(39). (ii) Additional studies provide evidence of the potential for two or more of these microorganisms found together in the CF airway to lead to worsened clinical outcomes (17,40,41).…”

Section: Using Computational Approaches To Identify Community Types F...mentioning

confidence: 99%

Community composition shapes microbial-specific phenotypes in a cystic fibrosis polymicrobial model system

Jean-Pierre

Hampton

Schultz

et al. 2022

Preprint

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Interspecies interactions can drive the emergence of unexpected microbial phenotypes that are not observed when studying monocultures. The cystic fibrosis (CF) lung consists of a complex environment where particular microbes, living as polymicrobial biofilm-like communities, are associated with negative clinical outcomes for persons with CF (pwCF). However, the current lack of in vitro models integrating the microbial diversity observed in the CF airway hampers our understanding of why polymicrobial communities are recalcitrant to therapy in this disease. Here, integrating computational approaches informed by clinical data, we built a mixed community of clinical relevance to the CF lung composed of Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus sanguinis and Prevotella melaninogenica. We developed and validated this model biofilm community with multiple isolates of these four genera. When challenged with tobramycin, a front-line antimicrobial used to treat pwCF, the microorganisms in the polymicrobial community show altered sensitivity to this antibiotic compared to monospecies biofilms. We observed that wild-type P. aeruginosa is sensitized to tobramycin in a mixed community versus monoculture, and this observation holds across a range of community relative abundances. We also report that LasR loss-of-function, a variant frequently detected in the CF airway, induces tolerance of P. aeruginosa to tobramycin specifically in the mixed community. The molecular basis of this community-specific recalcitrance to tobramycin for the LasR mutant variant is the increased production of redox-active phenazines. Our data support the importance of studying clinically-relevant model polymicrobial biofilms to understand community-specific traits relevant to infections.SIGNIFICANCE STATEMENTThe CF lung is colonized by biofilm-like microbial communities that exhibit both resistance and tolerance (collectively called “recalcitrance”) to antimicrobials used in the clinic. Here, we leveraged clinical data from pwCF to inform our understanding of communities exhibiting recalcitrance. We developed and validated an in vitro model that revealed novel, community-specific phenotypes relevant to the clinic. We used this model to explore the underlying mechanism associated with a community-specific emergent behavior. We posit that in vitro models of polymicrobial communities may help in developing new antimicrobial strategies to improve patient outcomes, and that the approach used here can be applied to other polymicrobial models.

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“…Resistance can be caused by resistance genes or the production of an enzyme (beta-lactamase). Resistance can also be developed by repetitive use or administration of high doses of antibiotics, as in patients with cystic fibrosis (Lamoureux et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidates

Shah,

Anwar,

Qasim

et al. 2023

Front. Microbiol.

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The management of infectious diseases has become more critical due to the development of novel pathogenic strains with enhanced resistance. Prevotella melaninogenica, a gram-negative bacterium, was found to be involved in various infections of the respiratory tract, aerodigestive tract, and gastrointestinal tract. The need to explore novel drug and vaccine targets against this pathogen was triggered by the emergence of antimicrobial resistance against reported antibiotics to combat P. melaninogenica infections. The study involves core genes acquired from 14 complete P. melaninogenica strain genome sequences, where promiscuous drug and vaccine candidates were explored by state-of-the-art subtractive proteomics and reverse vaccinology approaches. A stringent bioinformatics analysis enlisted 18 targets as novel, essential, and non-homologous to humans and having druggability potential. Moreover, the extracellular and outer membrane proteins were subjected to antigenicity, allergenicity, and physicochemical analysis for the identification of the candidate proteins to design multi-epitope vaccines. Two candidate proteins (ADK95685.1 and ADK97014.1) were selected as the best target for the designing of a vaccine construct. Lead B- and T-cell overlapped epitopes were joined to generate potential chimeric vaccine constructs in combination with adjuvants and linkers. Finally, a prioritized vaccine construct was found to have stable interactions with the human immune cell receptors as confirmed by molecular docking and MD simulation studies. The vaccine construct was found to have cloning and expression ability in the bacterial cloning system. Immune simulation ensured the elicitation of significant immune responses against the designed vaccine. In conclusion, our study reported novel drug and vaccine targets and designed a multi-epitope vaccine against the P. melaninogenica infection. Further experimental validation will help open new avenues in the treatment of this multi-drug-resistant pathogen.

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Prevotella melaninogenica, a Sentinel Species of Antibiotic Resistance in Cystic Fibrosis Respiratory Niche?

Cited by 9 publications

References 49 publications

Exploring the Cystic Fibrosis Lung Microbiome: Making the Most of a Sticky Situation

Exploring the Cystic Fibrosis Lung Microbiome: Making the Most of a Sticky Situation

Community composition shapes microbial-specific phenotypes in a cystic fibrosis polymicrobial model system

Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidates

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