Coordinated phenotype switching with large-scale chromosome flip-flop inversion observed in bacteria

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 25; pp. E1647 - E1656
• Main Authors: Cui, Longzhu, Neoh, Hui-min, Iwamoto, Akira, Hiramatsu, Keiichi
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 19.06.2012; National Acad Sciences
• Series: PNAS Plus
• Subjects: Anti-Bacterial Agents - pharmacology; antibiotic resistance; Bacteria; Bacteria - drug effects; Bacteria - genetics; bacterial infections; Biological Sciences; Blotting, Southern; Cells; Chromosome Inversion; chromosome inversions; Chromosomes; Chromosomes, Bacterial; Electrophoresis, Gel, Pulsed-Field; eukaryotic cells; Gene expression; genes; Genotype & phenotype; hemolysis; Microbial Sensitivity Tests; Morphology; Oligonucleotide Array Sequence Analysis; phenotype; PNAS Plus; prokaryotic cells; quantitative analysis; Stochastic Processes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1204307109

Genome inversions are ubiquitous in organisms ranging from prokaryotes to eukaryotes. Typical examples can be identified by comparing the genomes of two or more closely related organisms, where genome inversion footprints are clearly visible. Although the evolutionary implications of this phenomenon are huge, little is known about the function and biological meaning of this process. Here, we report our findings on a bacterium that generates a reversible, large-scale inversion of its chromosome (about half of its total genome) at high frequencies of up to once every four generations. This inversion switches on or off bacterial phenotypes, including colony morphology, antibiotic susceptibility, hemolytic activity, and expression of dozens of genes. Quantitative measurements and mathematical analyses indicate that this reversible switching is stochastic but self-organized so as to maintain two forms of stable cell populations (i.e., small colony variant, normal colony variant) as a bet-hedging strategy. Thus, this heritable and reversible genome fluctuation seems to govern the bacterial life cycle; it has a profound impact on the course and outcomes of bacterial infections.