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Langer, Angela; Moldovan, Adriana; Harmath, Christian; Joyce, Susan A.; Clarke, David J. und Heermann, Ralf (2017): HexA is a versatile regulator involved in the control of phenotypic heterogeneity of Photorhabdus luminescens.
In: PLOS One 12(4), e0176535 [PDF, 8MB]

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Abstract

Phenotypic heterogeneity in microbial communities enables genetically identical organisms to behave differently even under the same environmental conditions. Photorhabdus luminescens, a bioluminescent Gram-negative bacterium, contains a complex life cycle, which involves a symbiotic interaction with nematodes as well as a pathogenic association with insect larvae. P. luminescens exists in two distinct phenotypic cell types, designated as the primary (1 degrees) and secondary (2 degrees) cells. The 1 degrees cells are bioluminescent, pigmented and can support nematode growth and development. Individual 1 degrees cells undergo phenotypic switching after prolonged cultivation and convert to 2 degrees cells, which lack the 1 degrees specific phenotypes. The LysR- type regulator HexA has been described as major regulator of this switching process. Here we show that HexA controls phenotypic heterogeneity in a versatile way, directly and indirectly. Expression of hexA is enhanced in 2 degrees cells, and the corresponding regulator inhibits 1 degrees specific traits in 2 degrees cells. HexA does not directly affect bioluminescence, a predominant 1 degrees specific phenotype. Since the respective luxCDABE operon is repressed at the post-transcriptional level and transcriptional levels of the RNA chaperone gene hfq are also enhanced in 2 degrees cells, small regulatory RNAs are presumably involved that are under control of HexA. Another phenotypic trait that is specific for 1 degrees cells is quorum sensing mediated cell clumping. The corresponding pcfABCDEF operon could be identified as the first direct target of HexA, since the regulator binds to the pcfA promoter region and thereby blocks expression of the target operon. In summary, our data show that HexA fulfills the task as repressor of 1 degrees specific features in 2 degrees cells in a versatile way and gives first insights into the complexity of regulating phenotypic heterogeneity in Photorhabdus bacteria.

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