Patange Om, Breen Peter, Arsuffi Giulia, Ruvkun Gary
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Cell Biology and Physiology, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA.
Cell Rep. 2025 Jan 28;44(1):115170. doi: 10.1016/j.celrep.2024.115170. Epub 2025 Jan 8.
Caenorhabditis elegans proliferates poorly in the presence of abundant Actinobacteria from its natural ecology, but it is unknown why. Here, we show how perturbed levels of hydrogen sulfide modulate the growth rate of both C. elegans and Actinobacteria. From a forward genetic selection, we find C. elegans mutants with faster growth on an Actinobacteria Microbacterium species and mutant alleles of conserved cystathionine gamma-lyase (cth-2/CTH) that improve growth rate. Conversely, null alleles of cth-2 cause developmental arrest of animals grown on Actinobacteria, but not on Proteobacteria, which can be rescued by exogenous HS. We also find mutations in a leucine-rich-repeat gene that regulates cysteine and HS production, lrr-2/LRRC58. We place lrr-2 in the animal sulfur metabolism pathway by demonstrating its role in post-translationally regulating levels of cysteine dioxygenase (cdo-1/CDO1). Exogenously supplied HS inhibits the growth of Actinobacteria but not Proteobacteria. Thus, we conclude that the C. elegans-Actinobacteria interaction is mediated by HS.
秀丽隐杆线虫在其天然生态环境中存在大量放线菌的情况下增殖能力较差，但原因尚不清楚。在此，我们展示了硫化氢水平的扰动如何调节秀丽隐杆线虫和放线菌的生长速率。通过正向遗传学筛选，我们发现了在一种放线菌微杆菌属物种上生长更快的秀丽隐杆线虫突变体，以及能提高生长速率的保守胱硫醚γ-裂解酶（cth-2/CTH）的突变等位基因。相反，cth-2的无效等位基因会导致在放线菌上生长的动物发育停滞，但在变形菌上生长的动物不会，而外源性硫化氢可以挽救这种情况。我们还在一个调节半胱氨酸和硫化氢产生的富含亮氨酸重复序列基因lrr-2/LRRC58中发现了突变。通过证明其在翻译后调节半胱氨酸双加氧酶（cdo-1/CDO1）水平中的作用，我们将lrr-2置于动物硫代谢途径中。外源性提供的硫化氢会抑制放线菌的生长，但不会抑制变形菌的生长。因此，我们得出结论，秀丽隐杆线虫与放线菌之间的相互作用是由硫化氢介导的。
