Reprogramming of cells by lactic acid bacteria

Living organisms have been classified into three domains-archaea, eukaryota, and prokaryota-based on their cell structure and genetic evolution (Woese CR, Kandler O, Wheelis ML. Proc Natl Acad Sci USA 87:4576-4579, 1990). The eukaryotic cells have organelles that originated from prokaryotes living within these cells as endosymbionts (Martin W, Hoffmeister M, Rotte C, Henze K. Biol Chem 382:1521-1539. https://doi.org/10.1515/BC.2001.187, 2001). Endosymbionts affected the evolution and diversity of living organisms by horizontal gene transfer (Woese CR. Proc Natl Acad Sci USA 99:8742-8747. https://doi.org/10.1073/pnas.132266999, 2002; Timmis JN, Ayliffe MA, Huang CY, Martin W. Nat Rev Genet 5:123-135. https://doi.org/10.1038/nrg1271, 2004). The origin of eukaryotic cells was explained by the endosymbiotic theory, which has been advanced and substantiated with microbiological evidence (Margulis L. Origin of eukaryotic cells: Evidence and research implications for a theory of the origin and evolution of microbial, plant and animal cells on the precambrian earth. Yale University Press, New Heaven, 1970). The partnership between a primitive anaerobic eukaryotic predator cell and an aerobic bacterial cell was potentially established about 1.5 billion years ago. At present, it is widely believed that eubacteria infected archaebacteria, leading to the translocation of genomic DNA and the evolution of eukaryotic cells (Hartman H, Fedorov A. Proc Natl Acad Sci USA 99:1420-1425. https://doi.org/10.1073/pnas.032658599, 2002). Over time, endosymbiotic interactions and genomic scrambling in various organisms contributed to the generation of new organisms. To examine whether a bacterial infection can alter cell fate, human dermal fibroblast (HDF) cells were co-cultured with lactic acid bacteria (LAB), which are known to have beneficial effects on the physiology of the host. We previously showed that when HDF cells were incorporated with LAB, the LAB-incorporated HDF cells formed clusters and expressed a subset of common pluripotent markers. Moreover, the LAB-incorporated cell clusters could differentiate into cells of any of the three germ layers, indicating successful reprogramming of the host HDF cells by LAB. In this review, we discuss the nuclear reprogramming mechanisms in the existing examples of cellular reprogramming by bacteria.