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Phtheirospermum japonicum, a member of the Orobanchaceae family, is a facultative root parasitic plant that can survive without parasitizing the host. In contrast, obligate root parasitic plants such as Striga and Orobanche, which are also members of the Orobanchaceae family, cannot survive in the absence of the host. The germination of obligate root parasitic plants is typically induced by host root-derived strigolactones (SLs) at very low concentrations. The KAI2/HTL family proteins have been found to be involved in the perception of karrikin (KAR), a smoke-derived germination inducer and unidentified endogenous ligand, in non-parasitic plants. Obligate root parasitic plants possess uniquely diverged KAI2 clade genes, which are collectively referred to as KAI2d. Many of those have been shown to function as SL receptors. Intriguingly, the KAI2d clade genes are also conserved in P. japonicum, even though this plant does not require SLs for germination. The biochemical and physiological functions of the KAI2d proteins in P. japonicum remain unclear. Here, we report that some of these proteins can function as SL receptors in P. japonicum. Moreover, we found that one of them, PjKAI2d4, is highly sensitive to SLs when expressed in Arabidopsis, and it is similar to the sensitive SL receptors found in Striga and Orobanche. These results suggest that the KAI2d clade SL receptors play a crucial role not only in obligate parasites but also in facultative parasitic plants.

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Strigolactones (SLs) are plant hormones that regulate shoot branching. In addition, SLs act as compounds that stimulate the germination of root parasitic weeds, such as Striga spp. and Orobanche spp., which cause significant damage to agriculture worldwide. Thus, SL agonists have the potential to induce suicidal germination, thereby reducing the seed banks of root parasitic weeds in the soil. Particularly, phenoxyfuranone-type SL agonists, known as debranones, exhibit SL-like activity in rice and Striga hermonthica. However, little is known about their effects on Orobanche spp. In this study, we evaluated the germination-inducing activity of debranones against Orobanche minor. Analysis of structure-activity relationships revealed that debranones with electron-withdrawing substituents at the 2,4- or 2,6-position strongly induced the germination of Orobanche minor. Lastly, biological assays indicated that 5-(2-fluoro-4-nitrophenoxy)-3-methylfuran-2(5H)-one (test compound 61) induced germination to a comparable or even stronger extent than GR24, a well-known synthetic SL. Altogether, our data allowed us to infer that this enhanced activity was due to the recognition of compound 61 by the SLs receptor, KAI 2d, in Orobanche minor.

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Strigolactones (SLs) were initially discovered as germination inducers for root parasitic plants. In 2015, three groups independently reported the characterization of the SL receptor in the root parasitic plant Striga hermonthica, which causes significant damage to crop production, particularly in sub-Saharan Africa. The characterized receptors belong to HYPOSENSITIVE TO LIGHT/KARRIKIN INSENSITIVE2 (HTL/KAI2), which is a member of the α/ß-hydrolase protein superfamily. In non-parasitic plants, HTL/KAI2 perceives the smoke-derived germination inducer karrikin and a yet-unidentified endogenous ligand. However, root parasitic plants evolved a specific clade of HTL/KAI2 that has diverged from the KAI2 clade of non-parasitic plants. The S. hermonthica SL receptors are included in this specific clade, which is called KAI2 divergent (KAI2d). Orobanche minor is an obligate root holoparasitic plant that grows completely dependent on the host for water and nutrients because of a lack of photosynthetic ability. Previous phylogenetic analysis of KAI2 proteins in O. minor has demonstrated the presence of at least five KAI2d clade genes. Here, we report that KAI2d3 and KAI2d4 in O. minor have the ability to act as the SL receptors. They directly interact with SLs in vitro, and when expressed in Arabidopsis, they rescue thermo-inhibited germination in response to the synthetic SL analog GR24. In particular, KAI2d3 showed high sensitivity to GR24 when expressed in Arabidopsis, suggesting that this receptor enables highly sensitive SL recognition in O. minor. Furthermore, we provide evidence that these KAI2d receptors are involved in the perception of sesquiterpene lactones, non-strigolactone-type germination inducers.

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RATIONALE: Immune checkpoint inhibitors (ICIs) have shown efficacy for the treatment of various kinds of malignant tumors. However, ICIs can cause immune-related adverse events, such as arthritis. Nevertheless, the treatment of ICI-induced arthritis has not been established yet. Here we report a case of ICI-induced polyarthritis successfully treated using sarilumab and monitored using joint ultrasonography. PATIENT CONCERNS: A 61-year-old man presented with polyarthritis. He had been treated with nivolumab for recurrent renal cell carcinoma 11 months before. He developed ICI-induced nephritis (proteinuria and elevated serum creatinine) 3 months before, which resolved after discontinuing nivolumab for 1 month. Two months after resuming nivolumab, he developed polyarthralgia and joint swelling, which were suspected to be associated with nivolumab administration, and hence we discontinued nivolumab again. Laboratory tests revealed elevated C-reactive protein level and erythrocyte sedimentation rate, but were negative for rheumatoid factor and anti-cyclic citrullinated peptide antibody. Joint ultrasonography revealed active synovitis in several joints, but a joint X-ray revealed no bone erosion. DIAGNOSES: We diagnosed polyarthritis as ICI-induced arthritis because the findings were not typical of rheumatoid arthritis (no bone erosion and seronegativity) and the patient had already developed other immune-related adverse events (ICI-induced nephritis). INTERVENTIONS: After discontinuation of nivolumab, we started treatment with 15 mg daily prednisolone and 1000 mg daily sulfasalazine, although it was ineffective. Hence, we initiated 200 mg biweekly sarilumab. OUTCOMES: Following sarilumab administration, polyarthritis improved rapidly, and joint ultrasonography confirmed the rapid improvement of synovitis. Hence, we tapered off the glucocorticoid treatment. No recurrence of renal cell carcinoma was noted for 2 years after the initiation of sarilumab despite no anti-tumor therapy. LESSONS: Sarilumab may serve as a good treatment option for treating refractory ICI-induced polyarthritis. Joint ultrasonography may contribute to the evaluation of ICI-induced polyarthritis and monitoring the effects of treatments.

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