Chengshu Wang

Personal Profile

05/2020- Professor at the CAS Center for Excellence of Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, CAS.

01/2007-04/2020 Professor at the Institute of Plant Physiology and Ecology, Shanghai Institute of Biological Sciences, CAS.

01/2004-12/2006 Research associate (postdoc) at the Department of Entomology, University of Maryland.

07/2001-12/2003 Research associate (postdoc) at the School of Biological Sciences, University of Wales Swansea, UK.

09/1998-07/2001 Ph D in Microbiology, China Agricultural University, Beijing.

09/1993-07/1996 MSc in Plant Protection, Anhui Agricultural University, Hefei.

09/1989-07/1993 BSc in Plant Protection, Anhui Agricultural University, Hefei.

Research Work

There are about one thousands of known fungal species capable of killing insects, most of which are ascomycete fungi. The species like Metarhizium anisopliae, M. robertsii, M. acridum and Beauveria bassiana have been developed as environmentally friendly biological control agents against different insect pests. The species of Cordyceps militaris and Ophiocordyceps sinensis, however, are best known as traditional Chinese Medicines that have been used for hundreds of years in Eastern countries. By focusing on this group of fungi, our research interests include but are not limited to:

1) Fungus-insect interactions: Dual recognitions, fungal infection and immune invasion, and insect host immune defenses.

2) Biology and function of insect cuticular microbiome: assembly, dynamics and multipartite interactions.

3) Chemical biology of fungus-insect interactions: Biosynthetic mechanisms and biological function of fungal small molecules.

Main Achievements

1. Unveiling the convergent evolution and population genomic features of fungal entomopathogenicity

Entomopathogenic fungi (EPF) such as the ascomycete Metarhizium and Beauveria species have long been models for unveiling the mechanisms of fungus-insect interactions and as eco-friendly biocontrol agents against insect pests. However, until initiated by Dr. Wang, no EPF species had been genome sequenced. Commencing in 2008, he coordinated EPF genome projects with comparative and evolutionary genomic analyses of 20 ascomycete species including different Metarhizium, Beauveria and Cordyceps species (PLoS Genet, 2011; Genome Biol, 2011; Sci Rep, 2012; Chinese Sci Bull, 2013; PNAS, 2014; Genome Biol Evol, 2016; BMC Genomics, 2017). It was evident that fungal entomopathogenicity has evolved independently multiple times with convergent evolution to produce an "entomopathogen toolkit". We also performed a population genomic investigation of B. bassiana that has been deployed against Masson’s pine caterpillars for more than 20 years. It was evident that released strains can persist in the field to maintain sustainable control. No dilution effect was evident in the local population after inundative releases; however, population replacement could occur about every decade due to balancing selection, adaptive divergence, non-random outcrossing and isolate migration (ISME J, 2020). In addition to unveiling the evolution and population genomic feature of fungal entomopathogenicity, obtaining EPF genome information can facilitate genomic investigations of fungus-insect interactions and thereby development of cost-effective mycoinsecticides.

 

2. Elucidation of the biosynthetic mechanisms and chemical biology of diverse small molecules produced by EPF

With the obtained EPF genome information, we predicted the genome-wide biosynthetic gene clusters (BGCs) for each EPF species and performed serial chemical genetic studies. We elucidated the biosynthetic mechanisms and biological functions by which Metarhizium produces the insecticidal cyclopeptide destruxins (Dtxs; PNAS, 2012), the alkaloid mycotoxin swainsonine (SW; ACS Cell Biol, 2020), the triterpene helvolic acid (Microbiol Spectr, 2022), and a supercluster-derived set of compounds, ustilaginoidins, indigotides, pseurotins and mer-f3 (mBio, 2022). Similarly, we elucidated the responsible pathways for the bibenzoquinone oosporein (PNAS, 2015), beauveriolides (mSphere, 2020), tenellins (mBio, 2021) and bassicarbosides (PNAS, 2023) in Beauveria; the coupled biosynthesis of the adenosine analogs cordycepin (i.e., 3'-deoxyadenosine) and pentostatin (the anti-leukemia drug first identified in Streptomyces sp.) in Cordyceps militaris (Cell Chem Biol, 2017); and the medicinal molecule CsA in Tolypocladium (mBio, 2018). In contrast to SW-producing endophytes, we clarified that the plants colonized by Metarhizium had no detectable SW, which alleviated safety concern of using Metarhizium for insect pest control (ACS Chem Biol, 2020). The precursor pipecolic acid produced by Metarhizium for Dtxs and SW production could be taken up by plants to promote plant defenses against aphid and bacterial pathogen attacks (Sci China Life Sci, 2023). These works advanced our understanding of the mechanisms and diversity of secondary fungal metabolism.

 

3. Unveiling the diverse mechanisms involved in fungus-insect mutual sensing and interactions

With functional genetics studies, we unraveled an array of genes involved in mediating bilateral sensing and interactions between EPF and insect hosts. For example, we have recently found that a spore surface CFEM protein encoded by M. robertsii can be sensed by a Drosophila chemosensory protein to vigorously trigger hygienic grooming that wipes off parasite spores within a few hours post challenge (Curr Biol, 2023). Spores that are not wiped off produce an adhesive galactosaminogalactan mucilaginous matrix via a biosynthetic gene cluster (PLoS Pathog, 2021). The Wang group deleted different GPCR genes in M. robertsii and identified one in particular that is required for mediating fungal host recognition, whereas other GPCR genes jointly contribute to recognizing particular insect hosts (Sci China Life Sci, 2021). Following host recognition, the cellular autophagic process of M. robertsii is activated to mediate degradation of lipid droplets (LDs) and produce the high concentration of glycerol required for increasing turgor pressure in infected cells (Autophagy, 2013). It was further demonstrated that the direct entry of LDs into vacuoles (the microlipophagy machinery of LD degradation) is activated for rapid generation of turgor pressure (Autophagy, 2022). Unsurprisingly, different genes involved in LD biogenesis, storage and distribution are required for Metarhizium virulence (Environ Microbiol, 2016; 2018; Philos Trans R Soc B, 2019). Once entering the insect body cavity, a Tge1 effector secreted by M. robertsii can block the ？-glucans receptor GNBP3 and GNBP like-3, a co-receptor of ？-glucans, to suppress Drosophila immunity (Cell Rep, 2024). A M35 family metalloprotease of M. robertsii cleaves insect PPOs into nonfunctional fragments (Virulence, 2020). Similar to plant pathogens, the chitin-binding LysM proteins of B. bassiana are required for fungal virulence by evasion of host cellular immunity (PLoS Pathogens, 2017). These studies provide insights into the interactive mechanisms between fungi and insects, which advance our overall understanding of microbe-animal interactions.

 

4. Expanding the bilateral fungus-insect interactions to the multipartite regimes among EPF, ectomicrobiotas and hosts

As indicated above, EPF infect insects via cuticle penetration. The Wang group’s recent investigations revealed that the insect body surfaces are inhabited by diverse bacteria that can quickly propagate after insect molting to form defensive ectomicrobiotas against fungal infection (iScience, 2022). Likewise, ectomicrobiotas can be quickly re-assembled after the ecdysis of silkworm larvae, and a bacterial species obtained from the mulberry leaves can protect caterpillars against fungal parasites largely using a chitinolytic lysozyme (Microbiome, 2024). We then noticed that defensin-like antimicrobial peptide (AMP) genes are encoded in EPF genomes, and revealed that a defensin-like AMP of B. bassiana is required to overcome cuticular bacteria that protect insects (ISME J, 2023). Intriguingly, Metarhizium species such as M. robertsii do not possess defensin-like AMPs. We showed that instead of bacteriocides, Metarhizium produce the potent triterpene antibiotic helvolic acid, which mediates bacteriostatic inhibition of insect cuticular bacteria to facilitate infection (Microbiol Spectr, 2022). We also found that a super BGC, including three sub-clusters in M. robertsii, could be orchestrated by a master regulator to produce an antibiotic cocktail with synergistic activities against different bacteria to facilitate adaptation to diverse niches (mBio, 2022). Our data unveiled a novel type of fungal virulence factor and infection strategy that involves outcompeting insect cuticular microbiotas, and consequently expands investigation of bilateral interactions between fungi and insects to multi-interactive levels.

 

  Overall, we have published more than 120 papers in peer-reviewed journals including the invited review articles in various journals such as Trends Microbiol (2024), Trends Parasitol (2024), Curr Opin Microbiol (2023), Toxins (2020), Annu Rev Entomol (2017), Adv Genet (2016), PLoS Pathogens (2024; 2015) and Biological Control (2014).

Publications

1) Zhao P, Hong S, Li Y, Chen HM, Gao HC, Wang CS*. 2024. From phyllosphere to insect cuticles: silkworms gather antifungal bacteria from mulberry leaves to battle fungal parasite attacks. Microbiome, 12: 40.

 

2) Lu MT, Wei DX, Shang JM, Li SQ, Song SX, Luo YJ, Tang GR, Wang CS*. 2024. Suppression of Drosophila antifungal immunity by a parasite effector via blocking GNBP3 and GNBP-like 3, the dual receptors for β-glucans. Cell Reports, 43(1):113642.

 

3) Hong S, Shang JM, Sun YL, Tang GR, Wang CS*. 2024. Fungal infection of insects: Molecular insights and prospects. Trends in Microbiology, 32(3): 302-316.

 

4) Shang JM, Song SX, Wang CS*. 2024. Metarhizium robertsii. Trends in Parasitology, 40(2): 192-193.

 

5) Shang JM, Hong S, Wang CS*. 2024. Fights on the surface prior to fungal invasion of insects. PLoS Pathogens, 20(2): e1011994.

 

6) Li X-L, Sun Y, Yin Y, Zhan S, Wang CS*. 2023. A bacterial-like Pictet–Spenglerase drives the evolution of fungi to produce β-carboline glycosides together with separate genes. Proceedings of the National Academy of Sciences USA, 120(30): e2303327120.

 

7) Shang JM, Tang GR, Yang J, Lu MT, Wang C-Z, and Wang CS* (2023). Sensing of a spore surface protein by a Drosophila chemosensory protein induces behavioral defense against fungal parasitic infections. Current Biology 33(2): 276-286.

 

8) Hong S, Sun YL, Chen HM, Wang CS*. 2023. Suppression of the insect cuticular microbiomes by a fungal defensin to facilitate parasite infection. ISME Journal, 17(1): 1-11.

 

9) Luo FF#, Tang GR#, Hong S, Gong T, Xin X-F, Wang CS.* 2022. Promotion of Arabidopsis immune responses by a rhizosphere fungus via supply of pipecolic acid to plants and selective augment of phytoalexins. Science China Life Sciences, 10.1007/s11427-022-2238-8

 

10) Li B, Song SX, Wei XF, Tang GR, Wang CS*. 2022. Activation of microlipophagy during early infection of insect hosts by Metarhizium robertsii. Autophagy, 18(3): 608-623.

 

11) Mei LJ#, Wang XW#, Yin Y, Tang GR, Wang CS*. 2021. Conservative production of galactosaminogalactan in Metarhizium is responsible for appressorium mucilage production and topical infection of insect hosts. PLoS Pathogens, 17(6): e1009656. [Cover story]

 

12) Shang JM#, Shang YF#, Tang GR, Wang CS*. 2021. Identification of a key G-protein coupled receptor in mediating appressorium formation and fungal virulence against insects. Science China Life Science, 64 (3): 466-477.

 

13) Mei LJ, Chen MJ, Shang YF, Tang GR, Tao Y, Zeng L, Huang B, Li ZZ, Zhan S*, Wang CS*. 2020. Population genomics and evolution of a fungal pathogen after releasing exotic strains to control insect pests for 20 years. ISME J, 14(6): 1422-1434.

 

14) Luo FF, Hong S, Chen B, Yin Y, Tang GR, Hu FL, Zhang HZ, Wang CS*. 2020. Unveiling of swainsonine biosynthesis via a multi-branched pathway in fungi. ACS Chemical Biology, 15(9): 2476-2484.

 

15) Huang W, Hong S, Tang GR, Lu YZ, Wang CS*. 2019. Unveiling the function and regulation control of the DUF3129 family proteins in fungal infection of hosts. Philosophical Transactions of the Royal Society B: Biological Sciences, 374(1767): 20180321.

 

16) Wang CS*, Wang SB. 2017. Insect pathogenic fungi: genomics, molecular interactions, and genetic improvements. Annual Review of Entomology, 62: 73-90.

 

17) Xia YL, Luo FF, Shang YF, Chen PL, Lu YZ, Wang CS*. 2017. Fungal cordycepin biosynthesis is coupled with the production of the safeguard molecule pentostatin. Cell Chemical Biology, 24: 1479-1489.

 

18) Cen K, Li B, Lu YZ, Zhang SW, Wang CS*. 2017. Divergent LysM effectors contribute to the virulence of Beauveria bassiana by evasion of insect immune defenses. PLoS Pathogens, 13(9): e1006004.

 

19) Feng P, Shang YF, Cen K, Wang CS*. 2015. Fungal biosynthesis of the bibenzoquinone oosporein to evade insect immunity. Proceedings of the National Academy of Sciences USA, 112(36): 11365-11370.

 

20) Shang YF, Feng P, Wang CS*. 2015. Fungi that infect insects: altering host behavior and beyond. PLoS Pathogens, 11(8): e1005037.

 

21) Hu X, Xiao GH, Zheng P, Shang YF, Su Y, Zhang XY, Liu XZ, Zhan S, St. Leger RJ, Wang CS*. 2014. Trajectory and genomic determinants of fungal-pathogen speciation and host adaptation. Proceedings of the National Academy of Sciences USA, 111(47): 16796-16801.

 

22) Duan ZB, Chen YX, Huang W, Shang YF, Chen PL, Wang CS*. 2013. Linkage of autophagy to fungal development, lipid storage and virulence in Metarhizium robertsii. Autophagy, 9(4): 538-549.

 

23) Hu X, Zhang YJ, Xiao GH, Zheng P, Xia YL, Zhang XY, St Leger RJ, Liu XZ, Wang CS*. 2013. Genome survey uncovers the secrets of sex and lifestyle in caterpillar fungus. Chinese Science Bulletin, 58(23): 2846-2854.

 

24) Wang B, Kang QJ, Lu YZ, Bai LQ, Wang CS*. 2012. Unveiling the biosynthetic puzzle of destruxins in Metarhizium species. Proceedings of the National Academy of Sciences USA, 109(4): 1287-1292.

 

25) Zheng P, Xia YL, Xiao GH, et al., Wang CS*. 2011. Genome sequence of the insect pathogenic fungus Cordyceps militaris, a valued traditional Chinese medicine. Genome Biology, 12(11): R116.

 

26) Wang CS*, St Leger RJ*. 2007. A scorpion neurotoxin increases the potency of a fungal insecticide. Nature Biotechnology 25(12):1455-1456.