High Levels of the Xenorhabdus nematophila Transcription Factor Lrp Promote Mutualism with the Steinernema carpocapsae Nematode Host

Abstract

Xenorhabdus nematophila bacteria are mutualistic symbionts of Steinernema carpocapsae nematodes and pathogens of insects. The X. nematophila global regulator Lrp controls the expression of many genes involved in both mutualism and pathogenic activities, suggesting a role in the transition between the two host organisms. We previously reported that natural populations of X. nematophila exhibit various levels of Lrp expression and that cells expressing relatively low levels of Lrp are optimized for virulence in the insect Manduca sexta. The adaptive advantage of the high-Lrp-expressing state was not established. Here we used strains engineered to express constitutively high or low levels of Lrp to test the model in which highLrp-expressing cells are adapted for mutualistic activities with the nematode host. We demonstrate that high-Lrp cells form more robust biofilms in laboratory media than do low-Lrp cells, which may reflect adherence to host tissues. Also, our data showed that nematodes cultivated with high-Lrp strains are more frequently colonized than are those associated with low-Lrp strains. Taken together, these data support the idea that high-Lrp cells have an advantage in tissue adherence and colonization initiation. Furthermore, our data show that high-Lrp-expressing strains better support nematode reproduction than do their low-Lrp counterparts under both in vitro and in vivo conditions. Our data indicate that heterogeneity of Lrp expression in X. nematophila populations provides diverse cell populations adapted to both pathogenic (low-Lrp) and mutualistic (high-Lrp) states.IMPORTANCE Host-associated bacteria experience fluctuating conditions during both residence within an individual host and transmission between hosts. For bacteria that engage in evolutionarily stable, long-term relationships with particular hosts, these fluctuations provide selective pressure for the emergence of adaptive regulatory mechanisms. Here we present evidence that the bacterium Xenorhabdus nematophila uses various levels of the transcription factor Lrp to optimize its association with its two animal hosts, nematodes and insects, with which it behaves as a mutualist and a pathogen, respectively. Building on our previous finding that relatively low cellular levels of Lrp are optimal for pathogenesis, we demonstrate that, conversely, high levels of Lrp promote mutualistic activities with the Steinernema carpocapsae nematode host. These data suggest that X. nematophila has evolved to utilize phenotypic variation between high-and low-Lrp-expression states to optimize its alternating behaviors as a mutualist and a pathogen.KEYWORDS virulence modulation, phenotypic variation, symbiosis, colonization initiation

Selection of Bacterial Mutants in Late Infections: When Vector Transmission Trades Off against Growth Advantage in Stationary Phase

“…In fact, lrp mutants are poorly transmitted, which cannot be explained by a deficiency in reassociation with nematodes, as we found that IJs emitted from group 2 infections carried as many bacteria as those from group 1 infections. This observation contradicts the prediction of Cao et al (22) but supports previous findings by Sicard et al (19). Low transmission of group 2 comes instead from a sharp decrease in nematode reproduction, which is in agreement with earlier experimental results (20, 22) and corresponds with the well-established detrimental effect of secondary variants in mass production of S. carpocapsae (32).…”

“…This observation contradicts the prediction of Cao et al (22) but supports previous findings by Sicard et al (19). Low transmission of group 2 comes instead from a sharp decrease in nematode reproduction, which is in agreement with earlier experimental results (20, 22) and corresponds with the well-established detrimental effect of secondary variants in mass production of S. carpocapsae (32). We also found that IJs emitted from group 2 infections have lower survival during dispersal compared to group 1 infections, which is probably yet another indication that infections initiated with lrp mutants constitute an unfavorable environment for S. carpocapsae , which is consistent with the study of Cao et al (22).…”

Studying the Symbiotic Bacterium Xenorhabdus nematophila in Individual, Living Steinernema carpocapsae Nematodes Using Microfluidic Systems

“…Our third model entails population growth and death arising due to phenotypic switching. X. nematophila exhibits a phenotypic variation phenomenon termed virulence modulation, in which cells switch between mutualistic and pathogenic states ( 41 – 43 ). The IJ transmits X. nematophila from a niche in which it expresses mutualistic behaviors (the insect cadaver in which it supports nematode reproduction) to one in which it expresses pathogenic behaviors (the blood cavity of a newly infected living insect host) ( Fig.…”

Improving the Yield of Xenocoumacin 1 Enabled by In Situ Product Removal

“…( 1 − 3 ) These bacteria colonize in a specialized intestinal receptacle of the infective juvenile (IJ) form of the nematode, and together, they form an entomopathogenic complex that can infect and kill different insects. 2 , 4 − 6 To survive, the nematodes search for a susceptible insect host in soil, perforating the insect’s intestinal wall and migrating into the hemocoel. Once in the hemocoel, the nematode releases X. nematophila into the insect host’s hemolymph, and the bacteria produce immunosuppressive compounds and insect toxins to overcome the host immune system and kill it.…”