Some studies are interesting and thought-provoking, and some studies are just studies. But this new paper in journal Science is a beauty. One rarely comes across to this type of research.
As many of you many know, we harbor large numbers of friendly microorganisms inside (gut, lung) or outside (skin). In many aspects, these commensal microbes share characteristics, like LPS (endotoxin), with their pathogenic siblings. However, since commensal microbes can live with us in peace, they probably had acquired some properties to make such co-habitation possible.
Indeed, the authors, led by Andrew Goodman at the Yale University School of Medicine, found that unlike pathogenic microorganisms (E. coli, S. enterica, C. rodentium), major subsets of our commensal microbial world were highly resistant to several cationic anti-microbial peptides (AMP).
The authors determined that this increased resistance of commensals to AMP was relate to a single gene encoding enzyme, LpxF, responsible for removing phosphate group from LPS (component of microbial cell wall).
In vivo experiments with mono-colonization of LpxF-deficient mutant human commensal microbe, B. thetaiotaomicron, confirmed that unlike LpxF-complemented B. thetaiotaomicron, B. thetaiotaomicron deficient for LpxF was easily displaced by wild-type B. thetaiotaomicron in presence of pathogenic C. rodentium infection or chemical, DSS-induced inflammation. Non-virulent tir mutant C. rodentium or commensal SFB had no impact on LxpF-deficient B. thetaiotaomicron population stability.
Similar results were observed when 14 member of human gut flora were transplanted into germ-free mice and exposed to C. rodentium infection, implying that LxpF played important role in population stability during gut inflammation.
Finally, gut microbes obtained directly from healthy humans displayed similar resistance to AMP.
In summary, these results suggest that human gut microflora acquired resistance to its own host's anti-microbial peptides thus providing additional mechanism responsible for peaceful co-existence and gut ecological stability.
Of course, such resistance of gut commensals to AMP may pose problem when gut microbes invade inner systems, as during sepsis. So, this is a double-edge sword dilemma for host-microbe mutualism.
The experiments that are missing, in my opinion: (1) Repeat of experiments with anti-microbial peptide deficient mice models to confirm that population stability is indeed related to resistance to AMPs; (2) It is not clear how presence of LxpF-deficient commensal microbe could affect the severity of inflammation induced by C. rodentium.
David Usharauli
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