Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation

Cullen, Thomas W.; Schofield, Whitman B.; Barry, Natasha A.; Putnam, Emily E.; Rundell, Ethan A.; Trent, M. Stephen; Degnan, Patrick H.; Booth, Carmen J.; Yu, Hongbing; Goodman, Andrew L.

doi:10.1126/science.1260580

Cited by 346 publications

(336 citation statements)

References 55 publications

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“…Bacteroides strains (Dataset S1, Table S5) were anaerobically cultured on brain heart infusion (BHI; Becton Dickinson) agar supplemented with 50 μg/mL hemin (Sigma-Aldrich) and 0.5 μg/mL menadione (MP Biomedicals), in liquid tryptone-yeast-glucose (TYG) medium (26), or liquid minimal medium (22). Representative microbiome community members (Dataset S1, Table S5) were grown as previously described (27).…”

Section: Methodsmentioning

confidence: 99%

Human symbionts inject and neutralize antibacterial toxins to persist in the gut

Wexler

Bao

Whitney

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

180

203

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The human gut microbiome is a dynamic and densely populated microbial community that can provide important benefits to its host. Cooperation and competition for nutrients among its constituents only partially explain community composition and interpersonal variation. Notably, certain human-associated Bacteroidetes—one of two major phyla in the gut—also encode machinery for contact-dependent interbacterial antagonism, but its impact within gut microbial communities remains unknown. Here we report that prominent human gut symbionts persist in the gut through continuous attack on their immediate neighbors. Our analysis of just one of the hundreds of species in these communities reveals 12 candidate antibacterial effector loci that can exist in 32 combinations. Through the use of secretome studies, in vitro bacterial interaction assays and multiple mouse models, we uncover strain-specific effector/immunity repertoires that can predict interbacterial interactions in vitro and in vivo, and find that some of these strains avoid contact-dependent killing by accumulating immunity genes to effectors that they do not encode. Effector transmission rates in live animals can exceed 1 billion events per minute per gram of colonic contents, and multiphylum communities of human gut commensals can partially protect sensitive strains from these attacks. Together, these results suggest that gut microbes can determine their interactions through direct contact. An understanding of the strategies human gut symbionts have evolved to target other members of this community may provide new approaches for microbiome manipulation.

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Section: Methodsmentioning

confidence: 99%

Human symbionts inject and neutralize antibacterial toxins to persist in the gut

Wexler

Bao

Whitney

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

180

203

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“…87,88 One of the mechanisms includes lipopolysaccharide modifications and increased AMP resistance triggered by pathogen-induced inflammation. 87,88 Robust bioinformatics environments and computational tools are needed-especially infrastructure and tools that can operate with terabases and pentabases of microbiome data and that also can analyze different data types (generated in multiomics studies). The fundamental differences between sequence analysis of the genome of a single microorganism versus metagenome are that the sequence reads from the DNA of a single microbe can be assembled, aligned, and annotated easily (where a reference database exists), whereas most microbial genomes are closed, circular structures that is difficult to annotate and characterize.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic and Technical Challenges in Studying the Human Microbiome and Cancer Epidemiology

Verma

2016

Technol Cancer Res Treat

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This article reviews the significance of the microbiome in cancer epidemiology, mechanistic and technical challenges in the field, and characterization of the microbiome in different tumor types to identify biomarkers of risk, progression, and prognosis. Publications on the microbiome and cancer epidemiology were reviewed to analyze sample collection and processing, microbiome taxa characterization by 16S ribosomal RNA sequencing, and microbiome metabolite characterization (metabotyping) by nuclear magnetic resonance and mass spectrometry. The analysis identified methodology types, research design, sample types, and issues in integrating data from different platforms. Aerodigestive cancer epidemiology studies conducted by different groups demonstrated the significance of microbiome information in developing approaches to improve health. Challenges exist in sample preparation and processing (eg, standardization of methods for collection and analysis). These challenges relate to technology, data integration from ''omics'' studies, inherent bias in primer selection during 16S ribosomal RNA sequencing, the need for large consortia with well-characterized biospecimens, cause and effect issues, resilience of microbiota to exposure events (requires longitudinal studies), and expanding studies for fungal and viral diversity (most studies used bacterial 16S ribosomal RNA sequencing for microbiota characterization). Despite these challenges, microbiome and cancer epidemiology studies are significant and may facilitate cancer risk assessment, diagnosis, and prognosis. In the future, clinical trials likely will use microbiota modifications to improve the efficacy of existing treatments.

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“…Production of antimicrobial compounds seems to be a general phenomenon for most bacteria [19]. The search for new antimicrobial agents is a field of utmost importance.…”

Section: Discussionmentioning

confidence: 99%

Reexamining intra and extracellular metabolites produced by Pseudomonas aeruginosa

Shuja¹,

Jamil

2016

J Coast Life Med

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Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation

Cited by 346 publications

References 55 publications

Human symbionts inject and neutralize antibacterial toxins to persist in the gut

Human symbionts inject and neutralize antibacterial toxins to persist in the gut

Mechanistic and Technical Challenges in Studying the Human Microbiome and Cancer Epidemiology

Reexamining intra and extracellular metabolites produced by Pseudomonas aeruginosa

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