An osmosensing histidine kinase mediates dicarboximide fungicide resistance in Botryotinia fuckeliana (Botrytis cinerea)

Differential Role of HAMP-like Linkers in Regulating the Functionality of the Group III Histidine Kinase DhNik1p

“…As per the SMART database Nik1 orthologs from yeast contain five HAMP domains, whereas those from filamentous ascomycetes and basidiomycetes contain six and seven HAMP domains, respectively (14). Point mutations in the HAMP domains have been shown to affect fludioxonil sensitivity as well as osmosensing functions of Nik1 orthologs (8,15,16). The poly-HAMP module plays a very important role in the functionality of the group III HHK and appears to function both as sensor and regulator of its activity.…”

Interactions among HAMP Domain Repeats Act as an Osmosensing Molecular Switch in Group III Hybrid Histidine Kinases from Fungi

“…Two lines of evidence led us to believe that they may be importance for osmosensing by DhNik1p. First, several osmosensitive and fungicide-resistant mutants were identified that carried point mutations in HAMP domain repeat in Nik1 orthologs (17,26,27). Second, we have observed that a chimeric construct where the N-terminal nonkinase region (which is essential for its membrane localization and osmosensing) of DhSln1p (a Sln1p ortholog in D. hansenii) was swapped with the N-terminal region of DhNik1p containing HAMP repeats could also complement sln1 mutation in S. cerevisiae.…”

“…NIK1 orthologs from filamentous fungi are directly linked with the resistance to few important fungicidal agents used in agriculture. Point mutations in different HAMP domain repeats in Nik1p or its orthologs from B. fuckeliana and C. heterostrophus could confer varying degrees of drug resistance and osmosensitivity to the host (17,27,41). Thus, the structural insights about the HAMP domain repeats will not only help to understand these interesting mutants but also will aid in developing novel fungicides in the future.…”

“…These putative osmosensors appear to be ubiquitous in fungi (6). Nik1p of Neurospora crassa (also known as os-1) (15,16), Daf1p of Botryotinia fuckeliana (Botrytis cinerea) (17), Hik1p of Magnaporthe grisea (18), and CaNik1p of Candida albicans (19 -21) are few well known examples of this group. Group III HHKs are also shown to be involved in the hyphal development and virulence in few fungi.…”

“…Moreover, they have a unique N-terminal region consisting of HAMP domain repeats. The analysis of the fungicide-resistant field or laboratory isolates of N. crassa, B. cinerea, and Cochliobolus heterostrophus showed that many of these mutants harbor point mutations in the HAMP domain repeats of the respective Nik1 orthologs and therefore suggested that these repeats are functionally very important (17,26,27). HAMP domains are so named because of their frequent occurrence in proteins associated with signal transduction in prokaryotic and lower eukaryotic organisms, such as histidine kinases, adenyl cyclases, methyl accepting chemotaxis proteins and phosphatases (28).…”