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The Cancer-Associated Microbe Library reveals functional host-microbe interactions during colorectal cancer progression

ABSTRACT:

Functional characterization of microbes which colonize CRC is impeded by a lack of bacterial strains from tumor tissues. Here, we report the Cancer-Associated Microbe Library (CAM-L), comprising more than 3,000 viable bacterial isolates, representing 121 distinct species, and 60 matching organoid models from colorectal adenomas, adenocarcinomas, metastases, and adjacent tissue controls of 45 patients. CAM-L comprises 47 species not covered by large stool-based culture collections and two novel species of Fusobacterium and Granulicatella. In silico characterization reveals that CAM-L isolates encode a diversity of host-relevant functions that differ by disease state. We showcase the capacity for functional exploration with CAM-L isolates using three examples, covering adhesin variants of genotoxic Escherichia coli, bile salt deconjugation by metastasis-dwelling Enterococcus faecalis and glycoprotein modification by Clostridium perfringens. The CAM-L collection is set to help cancer microbiome research mature from association to systematic exploration of causality.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase

PROVIDER: MTBLS7385 | MetaboLights | 2026-02-08

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS7385_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS7385_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	s_MTBLS7385.txt	Txt

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Project description:The success of Enterococcus faecium and E. faecalis evolving as multi-resistant nosocomial pathogens is associated with their ability to acquire and share adaptive traits, including mobile genetic elements (MGE) encoding antimicrobial resistance. Here, we define the mobilome in representative successful hospital associated genetic lineages, E. faecium ST17 (n=10) and ST78 (n=10), E. faecalis ST6 (n=10) and ST40 (n=10) using DNA microarray analyses. The hybridization patterns of 272 targets representing plasmid backbones (n=85), transposable elements (n=85), resistance determinants (n=67), prophages (n=29), and CRISPR-cas sequences (n=6) separated the strains according to species, and for E. faecalis also according to STs. Although plasmids belonging to the RCR-, Rep_3-, RepA_N- and Inc18-families were well represented with no significant differences in prevalence, the presence of specific replicon classes differed highly between the species; E. faecium was dominated by rep17/pRUM, rep2/pRE25, rep14/EFNP1 and rep20/pLG1 and E. faecalis by rep9/pCF10, rep2/pRE25 and rep7. Tn916-elements conferring tetracycline resistance (tetM) were found in all E. faecalis strains, but only in two E. faecium strains. A significant higher prevalence of IS256-, IS3-, ISL3-, IS200/IS605-, IS110-, IS982-, and IS4-transposases were detected in E. faecium, and of IS110-, IS982- and IS1182-transposases in E. faecalis ST6 compared to ST40. Notably, the transposases of IS981, ISEfm1 and IS1678 which have only been reported in few enterococcal isolates, were well represented in the E. faecium strains. E. faecalis ST40 strains harboured possible functional CRISPR-Cas systems, and still resistance and prophage sequences were generally well represented. Gene targets defined as the enterococcal mobilome, including plasmids, IS elements and transposons, resistance determinants, prophage sequences and CRISPR-Cas systems were highly prevalent, underlining their potential importance in the evolution of hospital associated STs. An association between axe-txe to the RepA_N-family and ω-ε-ζ to the Inc18-family, implicates the contribution of TA-systems in stable plasmid maintenance carrying virulence and resistance determinants in enterococci. The concurrent presence of defined MGE and their associated resistance markers was generally confirmed and illustrates the importance of horizontal gene transfer in the development of multidrug resistant enterococci.

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The Cancer-Associated Microbe Library reveals functional host-microbe interactions during colorectal cancer progression

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