Commuting between kingdoms: The biosynthesis of the only nonplant stilbene 1 from Photorhabdus bacteria has been solved by identification of all the genes involved in its biosynthesis and by feeding experiments. Stilbene 1 is derived from the condensation of two β‐ketoacyl thioesters and is required for the normal development of Heterorhabditis nematodes, the natural host of Photorhabdus.
Staphylococcal immunoglobulin-binding protein, Sbi, is a 436-residue protein produced by many strains of Staphylococcus aureus. It was previously characterized as being cell surface-associated and having binding capacity for human IgG and  2 -glycoprotein I. Here we show using small angle x-ray scattering that the proposed extracellular region of Sbi (Sbi-E) is an elongated molecule consisting of four globular domains, two immunoglobulin-binding domains (I and II) and two novel domains (III and IV). We further show that together domains III and IV (Sbi-III-IV), as well as domain IV on its own (Sbi-IV), bind complement component C3 via contacts involving both the C3dg fragment and the C3a anaphylatoxin domain. Preincubation of human serum with either Sbi-E or Sbi-III-IV is inhibitory to all complement pathways, whereas domain IV specifically inhibits the alternative pathway. Monitoring C3 activation in serum incubated with Sbi fragments reveals that Sbi-E and Sbi-III-IV both activate the alternative pathway, leading to consumption of C3. By contrast, inhibition of this pathway by Sbi-IV does not involve C3 consumption. The observation that Sbi-E activates the alternative pathway is counterintuitive to intact Sbi being cell wall-associated, as recruiting complement to the surface of S. aureus would be deleterious to the bacterium. Upon re-examination of this issue, we found that Sbi was not associated with the cell wall fraction, but rather was found in the growth medium, consistent with it being an excreted protein. As such, our data suggest that Sbi helps mediate bacterial evasion of complement via a novel mechanism, namely futile fluid-phase consumption.
SummaryPhotorhabdus luminescens is a species of Gramnegative bacteria that is pathogenic to insects while also maintaining a mutualistic association with nematodes from the family Heterorhabditis. P. luminescens elaborates an extensive secondary metabolism during the post-exponential phase of growth that includes the production of an antibiotic called 3-5-dihydroxy-4-isopropylstilbene (ST), an anthraquinone pigment (AQ) and bioluminescence. In this study we identified a mutant that was unable to produce ST, AQ and light. This mutation was found to be in the mdh gene, encoding malate dehydrogenase, a key enzyme in the tricarboxylic acid (TCA) cycle. Interestingly the mdh mutant was unaffected in virulence but was unable to support nematode growth and development in vivo or in vitro. This clearly establishes that secondary metabolism in P. luminescens is required for the mutualistic interaction with the nematode. Furthermore, the construction of mutations in key genes in other central metabolic pathways confirmed the critical role for the TCA cycle in both secondary metabolism and mutualism, but not in virulence. Therefore, we conclude that the TCA cycle is required for the transition of P. luminescens from pathogen to mutualist implicating the involvement of a metabolic switch in the regulation of lifestyle decisions in this bacterium.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.