<i>Prevotella denticola</i> Lipopolysaccharide from a Cystic Fibrosis Isolate Possesses a Unique Chemical Structure

Lorenzo, Flaviana Di; Silipo, Alba; Matier, T.; Hanuszkiewicz, Anna; Elborn, J. Stuart; Lanzetta, Rosa; Sturiale, Luisa; Scamporrino, Andrea; Garozzo, Domenico; Valvano, Miguel A.; Tunney, Michael; Molinaro, Antonio

doi:10.1002/ejoc.201600037

“…In contrast, P. melaninogenica produced the greatest variety of short-chain fatty acids (associated with inflammation) amongst five tested anaerobes [18], and P. denticola shares similarities in its lipid A moieties to P. intermedia (a known pathogenic species), pointing towards pro-inflammatory traits [58]. Finally, certain strains of the periodontal disease-associated species, P. nigrescens, a close relative of P. intermedia, are thought to encode an enzymatic cell hydrolysis mechanism that destroys tissues.…”

Section: Resultsmentioning

confidence: 89%

Genomic diversity and antimicrobial resistance of Prevotella species isolated from chronic lung disease airways

Webb

¹

,

Olagoke

²

,

Baird

³

et al. 2022

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Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are characterized by increasingly frequent acute pulmonary exacerbations that reduce life quality and length. Human airways are home to a rich polymicrobial environment, which includes members of the obligately anaerobic genus Prevotella . Despite their commonness, surprisingly little is known about the prevalence, role, genomic diversity and antimicrobial resistance (AMR) potential of Prevotella species and strains in healthy and diseased airways. Here, we used comparative genomics to develop a real-time PCR assay to permit rapid Prevotella species identification and quantification from cultures and clinical specimens. Assay specificity was validated across a panel of Prevotella and non- Prevotella species, followed by PCR screening of CF and COPD respiratory-derived cultures. Next, 35 PCR-positive isolates were subjected to whole-genome sequencing. Of eight identified Prevotella species, P. histicola , P. melaninogenica , P. nanceiensis , P. salivae and P. denticola overlapped between participant cohorts. Phylogenomic analysis revealed considerable interhost but limited intrahost diversity, suggesting patient-specific lineages in the lower airways, probably from oral cavity aspirations. Correlation of phenotypic AMR profiles with AMR genes identified excellent correlation between tetQ presence and decreased doxycycline susceptibility, and ermF presence and decreased azithromycin susceptibility and clindamycin resistance. AMR rates were higher in the CF isolates, reflecting greater antibiotic use in this cohort. All tested Prevotella isolates were tobramycin-resistant, providing a potential selection method to improve Prevotella culture retrieval rates. Our addition of 35 airway-derived Prevotella genomes to public databases will enhance ongoing efforts to unravel the role of this diverse and enigmatic genus in both diseased and healthy lungs.

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“…For instance, P. melaninogenica, P. salivae , and P. nanceiensis may inhibit non-typeable Haemophilus influenzae -induced pro-inflammatory cytokine production by lung dendritic cells 52 , increased P. melaninogenica prevalence in CF airways has been associated with improved lung function 15 , and P. histicola can mute pro-inflammatory pathways triggered by P. aeruginosa in CF airways 55 . In contrast, P. melaninogenica produced the greatest variety of short-chain fatty acids (associated with inflammation) amongst five tested anaerobes 18 , and P. denticola shares similarities in its lipid A moieties to P. intermedia (a known pathogenic species), pointing towards pro-inflammatory traits 56 . Finally, certain strains of the periodontal disease-associated species, P. nigrescens , a close relative of P. intermedia , are thought to encode an enzymatic cell hydrolysis mechanism that destroys tissues.…”

Section: Resultsmentioning

confidence: 92%

Genomic diversity and antimicrobial resistance of Prevotella spp. isolated from chronic lung disease airways

Webb

¹

,

Olagoke

²

,

Baird

³

et al. 2021

Preprint

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Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are characterised by increasingly frequent acute pulmonary exacerbations that reduce life quality and length. Human airways are home to a rich polymicrobial environment, including members of the obligately anaerobic genus, Prevotella. Despite their commonness, surprisingly little is known about the prevalence, role, genomic diversity, and antimicrobial resistance (AMR) potential of Prevotella species/strains in healthy and diseased airways. Here, we used comparative genomics to develop a real-time PCR assay to permit rapid Prevotella spp. quantification from cultures and clinical specimens. Assay specificity was validated across a panel of Prevotella and non-Prevotella species, followed by PCR screening of CF and COPD respiratory-derived cultures. Next, 35 PCR-positive isolates were subjected to whole-genome sequencing. Of eight identified species, P. histicola, P. melaninogenica, P. nanceiensis, P. salivae and P. denticola overlapped between participant cohorts. Phylogenomic analysis revealed considerable interhost but limited intrahost diversity, indicating patient-specific lineages rather than patient-to-patient transmission. Correlation of phenotypic AMR profiles with AMR gene presence identified excellent correlation between tetQ presence and decreased doxycycline susceptibility, and ermF presence and decreased azithromycin susceptibility and clindamycin resistance. AMR rates were higher in the CF isolates, reflecting greater antibiotic use in this cohort. All tested Prevotella isolates were tobramycin-resistant, providing a potential selection method to improve Prevotella culture retrieval rates. Our addition of 35 airway-derived Prevotella genomes to public databases will enhance ongoing efforts to unravel the role of this diverse and enigmatic genus in both chronic respiratory diseases and healthy lungs.

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“…The commensal and protective role of core throat bacteria found here and also in healthy subjects is still not elucidated; especially, the specific role of anaerobes in the lower airways remains controversial [ 30 ]. However, it was demonstrated that Prevotella and other anaerobes exhibit antimicrobial activities and a specific strain of Prevotella possessing an altered LPS had less immune-stimulatory activities [ 31 , 32 ]. Our data cannot exclude the hypothesis that CFTR mutation is modifying the niches and the regional growth for specific CF pathogens in the lungs and that those modifications are the driving force of the establishment of pathogens in the lungs.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Oropharyngeal Microbiota from Children with Asthma and Cystic Fibrosis

Boutin

¹

,

Depner²,

Stahl

³

et al. 2017

Mediators of Inflammation

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A genuine microbiota resides in the lungs which emanates from the colonization by the oropharyngeal microbiota. Changes in the oropharyngeal microbiota might be the source of dysbiosis observed in the lower airways in patients suffering from asthma or cystic fibrosis (CF). To examine this hypothesis, we compared the throat microbiota from healthy children (n = 62) and that from children with asthma (n = 27) and CF (n = 57) aged 6 to 12 years using 16S rRNA amplicon sequencing. Our results show high levels of similarities between healthy controls and children with asthma and CF revealing the existence of a core microbiome represented by Prevotella, Streptococcus, Neisseria, Veillonella, and Haemophilus. However, in CF, the global diversity, the bacterial load, and abundances of 53 OTUs were significantly reduced, whereas abundances of 6 OTUs representing opportunistic pathogens such as Pseudomonas, Staphylococcus, and Streptococcus were increased compared to those in healthy controls controls and asthmatics. Our data reveal a core microbiome in the throat of healthy children that persists in asthma and CF indicating shared host regulation favoring growth of commensals. Furthermore, we provide evidence for dysbiosis with a decrease in diversity and biomass associated with the presence of known pathogens consistent with impaired host defense in children with CF.

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Prevotella denticola Lipopolysaccharide from a Cystic Fibrosis Isolate Possesses a Unique Chemical Structure

Cited by 12 publications

References 68 publications

Genomic diversity and antimicrobial resistance of Prevotella species isolated from chronic lung disease airways

Genomic diversity and antimicrobial resistance of Prevotella species isolated from chronic lung disease airways

Genomic diversity and antimicrobial resistance of Prevotella spp. isolated from chronic lung disease airways

Comparison of Oropharyngeal Microbiota from Children with Asthma and Cystic Fibrosis

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