Examining Pathogenic and Mutualistic Regulatory Networks in the Bacterium Xenorhabdus nematophila

Xenorhabdus nematophila, a Gram-negative bacterium, forms a mutualistic association with the entomopathogenic nematode Steinernema carpocapsae, and also is a pathogen that can kill a wide range of insects, and therefore provides us an opportunity to study the underlying mechanisms of both types of interactions. The successful adaptation of X. nematophila to each of its hosts requires coordinated expression of cellular factors in response to changes in host environments. The work presented here examines the relationships among the known regulators involved in adaptation and reveals new factors that contribute to the regulatory network.;A microarray analysis was performed to examine the global transcriptomes of LrhA (LysR homologue A) and Lrp (leucine-responsive regulatory protein). It revealed that LrhA, which was initially regarded only as a regulator of activities involved in insect virulence and degradation has wider effects on cellular functions, including nutrient and energy metabolism, transport and secretion, and signal transduction. The analysis of Lrp regulon not only confirmed its global regulator function in mutualism through the regulation of nematode colonization genes nilABC and in pathogenesis through activation of LrhA, but also revealed that the Lrp negatively regulates the transcription factor RpoS which is essential in mutualism, and the Cas system, a bacterial defense system against phage and other invading exogenous DNA elements.;Charcterization of the RpoS regulon suggests that it affects bacterial mutualism by mediating resistance to reactive-oxygen-species, growth under stress, and micro-aerobic conditions, and regulation of nutrient uptake and transport. Studies on the Cas system revealed its role in regulating bacterial mutualism potentially by affecting bacterial phenotypic variation and providing resistance to phage. They also suggest the Cas system may regulate the expression of endogenous X. nematophila genes.;Through the study of the regulatory networks of X. nematophila, this work provides useful information for us to understand the complex mechanisms of X. nematophila-host interactions, and allows us to gain valuable insights on both bacterial pathogenesis and mutualism in other systems. General knowledge obtained on how bacteria make the transition between pathogenic and mutualistic states will also help us control diseases involving human beings, animals and plants.