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mSystems
2017 ; 2
(4
): ? Nephropedia Template TP
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Metabolic Fingerprints from the Human Oral Microbiome Reveal a Vast Knowledge Gap
of Secreted Small Peptidic Molecules
#MMPMID28761934
Edlund A
; Garg N
; Mohimani H
; Gurevich A
; He X
; Shi W
; Dorrestein PC
; McLean JS
mSystems
2017[Jul]; 2
(4
): ? PMID28761934
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Recent research indicates that the human microbiota play key roles in maintaining
health by providing essential nutrients, providing immune education, and
preventing pathogen expansion. Processes underlying the transition from a healthy
human microbiome to a disease-associated microbiome are poorly understood,
partially because of the potential influences from a wide diversity of
bacterium-derived compounds that are illy defined. Here, we present the analysis
of peptidic small molecules (SMs) secreted from bacteria and viewed from a
temporal perspective. Through comparative analysis of mass spectral profiles from
a collection of cultured oral isolates and an established in vitro multispecies
oral community, we found that the production of SMs both delineates a temporal
expression pattern and allows discrimination between bacterial isolates at the
species level. Importantly, the majority of the identified molecules were of
unknown identity, and only ~2.2% could be annotated and classified. The catalogue
of bacterially produced SMs we obtained in this study reveals an undiscovered
molecular world for which compound isolation and ecosystem testing will
facilitate a better understanding of their roles in human health and disease.
IMPORTANCE Metabolomics is the ultimate tool for studies of microbial functions
under any specific set of environmental conditions (D. S. Wishart, Nat Rev Drug
Discov 45:473-484, 2016, https://doi.org/10.1038/nrd.2016.32). This is a great
advance over studying genes alone, which only inform about metabolic potential.
Approximately 25,000 compounds have been chemically characterized thus far;
however, the richness of metabolites such as SMs has been estimated to be as high
as 1 × 10(30) in the biosphere (K. Garber, Nat Biotechnol 33:228-231, 2015,
https://doi.org/10.1038/nbt.3161). Our classical, one-at-a-time activity-guided
approach to compound identification continues to find the same known compounds
and is also incredibly tedious, which represents a major bottleneck for global SM
identification. These challenges have prompted new developments of databases and
analysis tools that provide putative classifications of SMs by mass spectral
alignments to already characterized tandem mass spectrometry spectra and
databases containing structural information (e.g., PubChem and AntiMarin). In
this study, we assessed secreted peptidic SMs (PSMs) from 27 oral bacterial
isolates and a complex oral in vitro biofilm community of >100 species by using
the Global Natural Products Social molecular Networking and the DEREPLICATOR
infrastructures, which are methodologies that allow automated and putative
annotation of PSMs. These approaches enabled the identification of an untapped
resource of PSMs from oral bacteria showing species-unique patterns of secretion
with putative matches to known bioactive compounds.
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