A highly conserved and globally prevalent cryptic plasmid is among the most numerous mobile genetic elements in the human gut
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Abstract
Plasmids are extrachromosomal genetic elements that often encode fitness enhancing features. However, many bacteria carry ‘cryptic’ plasmids that do not confer clear beneficial functions. We identified one such cryptic plasmid, pBI143, which is ubiquitous across industrialized gut microbiomes, and is 14 times as numerous as crAssphage, currently established as the most abundant genetic element in the human gut. The majority of mutations in pBI143 accumulate in specific positions across thousands of metagenomes, indicating strong purifying selection. pBI143 is monoclonal in most individuals, likely due to the priority effect of the version first acquired, often from one’s mother. pBI143 can transfer between Bacteroidales and although it does not appear to impact bacterial host fitness in vivo , can transiently acquire additional genetic content. We identified important practical applications of pBI143, including its use in identifying human fecal contamination and its potential as an inexpensive alternative for detecting human colonic inflammatory states.
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In these assays, we found that pBI143 was indeed transferred from the donor to the recipient strains at a frequency of 5 x 10-7 and 3 x 10-6transconjugants per recipient, respectively (Supplementary Fig. 2).
wow, this is a really exciting result, and also exciting to see that you were able to get a positive hit from something that originated from a hypothesis from metagenomic data and validate it with cultured isolates - well done!
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Sequencing depth did not explain this observation, as pBI143 was highly covered (i.e., >50X)
I am wondering if in addition to coverage you calculated breadth - as in how much of the plasmid was covered at 50X for whichever version of PBI143 was detected? I've found this to be an important statistic to add for elements that might be highly conserved or similar to other sequences.
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Our findings reveal the astonishing success of pBI143 in the human gut, where it occurs in up to 92% of individuals in industrialized countries with copy numbers 14 times higher on average than crAssphage, the most abundant phage in the human gut. We also demonstrate the potential of pBI143 as a cost-effective biomarker to assess the extent of stress that microbes experience in the human gut, and as a sensitive means to quantify the level of human fecal contamination in environmental samples.
This paragraph summarizing the main results is written so well, and in such an exciting way. I totally wasn't expecting the last sentence previewing a way to detect levels of fecal contamination in environmental samples, and I'm excited to read those results!
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