If you've ever played the childhood game of “hide and seek,” in which you try to conceal yourself from others, you know the outcome. “Ready or not, here I come!” eventually leads to “You're It!”

It's somewhat like that when plant-parasitic nematodes (microscopic round worms) play “chemical hide and seek” with their plant host, says plant pathologist  Shahid Masood Siddique, an assistant professor in the UC Davis Department of Entomology and Nematology.

“The success of plant-parasitic nematodes depends on their ability to locate a suitable host in the soil,” says Siddique, corresponding author of the newly published Spotlight article, “Chemical Hide and Seek: Nematode's Journey to Its Plant Host,” in the journal Molecular Plant.

Nematodes can be deadly to plants, not only because of the direct damage they cause (they extract water and nutrients from their hosts such as wheat, soybeans, sugar beets, citrus, coconut, corn, peanuts, potato, rice, cotton and bananas) but the role of some species as virus vectors.

“Plant-parasitic nematodes are among the most destructive agricultural pests, causing more than $100 billion in losses per year in the United States,” Siddique said, noting that nematodes are especially damaging to potato, soybean and wheat crops.

Although the success of nematodes depends on their ability to locate a suitable host in the soil, what attracts them to their host “has largely remained unknown,” wrote the four-member UC Davis team of Siddique, Natalie Hamada, Henok Zemene Yimer and Valerie Williams. “Recent studies have revealed that host-seeking by nematodes is a complex process that involves multiple stages in the interaction.”

“Most damage is caused by a small group of root-infecting sedentary endoparasitic nematodes including cyst nematodes and root-knot nematodes (RKNs),” the team of UC Davis researchers wrote in their abstract. “Second stage juveniles (J2s) of plant-parasitic nematodes hatch from eggs into the soil and localize to the roots of host plants. The success of these non-feeding J2s depends on their ability to locate and infect a suitable host.”

For eight decades, scientists have researched the attraction of plant-parasitic nematodes to the host root, ever since the pioneering Maurice Blood Linford (1901-1960) of the University of Illinois, Urbana, Ill., observed in 1939 that the larvae of root-knot nematodes congregate in the cell elongation region behind the root cap.

“Both volatile and soluble components in the rhizosphere have been shown to influence nematode movement,” the UC Davis researchers wrote. “Methyl salicylate, a volatile chemical root signal, has been demonstrated to be a strong root attractant for RKN towards several Solanaceous plants (nightshade family). The non-volatile tomato root exudate quercetin was shown to elicit concentration dependent attraction or repulsion effect against Meloidogyne incognita to host root. Three recent studies have revealed that the recognition of and response to hosts by infective juveniles is a complex process that involves multiple stages in the interaction.”

Siddique focuses his research on basic as well as applied aspects of interaction between parasitic nematodes and their host plants. “The long-term object of our research is not only to enhance our understanding of molecular aspects of plant–nematode interaction but also to use this knowledge to provide new resources for reducing the impact of nematodes on crop plants in California.”  

Bruce Hammock today

The legendary Bruce Hammock, UC Davis distinguished professor who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center--is featured in the current edition of American Entomologist.

Entomologist Marlin Rice, a past president of the Entomological Society of America (ESA), penned the piece, titled "Bruce D. Hammock: Science Should Be Fun!"

Wrote Rice: "Bruce D. Hammock is widely known for his groundbreaking research in insect physiology, toxicology, pharmacology, and experimental therapeutics. Early contributions were in fundamental regulatory biology, development of both small molecules and recombinant viruses as environmentally friendly pesticides, and the application of accelerator mass spectrometry to biological science. His laboratory pioneered the use of immunoassay for the analysis of human and environmental exposure to pesticides and other contaminants.His laboratory provides graduate training that is diverse in disciplines and research areas. He recently formed a company, EicOsis, to develop an orally active non-addictive drug for inflammatory and neuropathic pain for humans and companion animals."

Hammock, who joined the UC Davis faculty in 1980 from UC Riverside, has directed the UC Davis Superfund Research Program (funded by the National Institutes of Health's National Institute of Environmental Health Sciences) for nearly four decades. He is a member of the National Academy of Sciences, and a fellow of the National Academy of Inventors and ESA.

A native of Little Rock, Ark., Bruce received his bachelor's degree in entomology (with minors in zoology and chemistry) magna cum laude from Louisiana State University, Baton Rouge, in 1969. He received his doctorate in entomology-toxicology from UC Berkeley in 1973 with John Casida at UC Berkeley. Hammock served as a public health medical officer with the U.S. Army Academy of Health Science, San Antonio, and as a postdoctoral fellow at the Rockefeller Foundation, Department of Biology, Northwestern University, Evanston, Ill.

Read the feature story here.

Some Related Links:

• Bruce Hammock and EicOsis, Innovator of the Year
• Bruce Hammock Receives $6 Million Grant
• Bruce Hammock Water Balloon Battle: 15 Minutes of Aim
• Research Could Lead to Drug to Prevent or Reduce Autism, Schizophrenia 
• Hammock Lab Union Draws 100 Scientists from 10 Countries
• Bruce Hammock: Scientist Extraordinaire

(Editor's Note: Thanks to Lisa Junker, ESA's director of publications, communications and marketing, who reached out to "our publishers at Oxford" to grant free community access to this feature story in American Entomologist)

(Embargo lifted at noon, Pacific Daylight Time)

DAVIS--Newly published research in the Proceedings of the National Academy of Sciences (PNAS) indicates that a drug discovered and developed in the laboratory of Bruce Hammock,UC Davis Department of Entomology and Nematology, may have a major role in preventing and treating llnesses associated with obesity.

More than 43 percent of adults in the United States are obese, according to the Center for Disease Control and Prevention (CDC). Obesity increases the risk of coronary artery disease, stroke, type 2 diabetes, and certain kinds of cancer.

The drug, a soluble epoxide hydrolase (sEH) inhibitor, appears to regulate “obesity-induced intestinal barrier dysfunction and bacterial translocation,” the 12-member team of researchers from UC Davis, University of Massachusetts and University of Michigan discovered. The same non-opioid drug is being investigated in human clinical safety trials in Texas to see if it blocks chronic pain associated with diseases such as spinal cord injury, diabetes and inflammatory bowel disease. 

The research, funded by multiple federal grants, is titled “Soluble Epoxide Hydrolase Is an Endogenous Regulator of Obesity-Induced Intestinal Barrier Dysfunction and Bacterial Translocation.”

“Obesity usually causes the loss of tight junctions and leaky gut,” said first author Yuxin Wang, a postdoctoral researcher who joined the Hammock lab in 2019 from the Department of Food Sciences, University of Massachusetts, Amherst. “In normal conditions, the gut mucosal barrier is like a defender to protect us from the ‘dirty things' in the lumen, such as bacteria and endotoxin. For obese individuals, the defender loses some function and leads to more ‘bad things' going into the circulation system, causing systemic or other organ disorders.”

Although intestinal dysfunction and other problems enhancing bacterial translocation underlies many human diseases, “the mechanisms remain largely unknown,” said Wang, who holds a doctorate in biochemistry and molecular biology from the Chinese Academy of Sciences. “What we found is sEH inhibition can repair the defender function (barrier function), decrease the ‘bad things' going into the blood (bacteria translocation), and reduce inflammation of fat.”

“Our research shows that sEH is a novel endogenous regulator of obesity-induced intestinal barrier dysfunction and bacterial translocation,” said corresponding author Guodong Zhang, a former researcher in the Hammock lab and now with the Food Science Department and Molecular and Cellular Biology Graduate Program at the University of Massachusetts. “To date, the underlying mechanisms for obesity-induced intestinal barrier dysfunction remain poorly understood. Therefore, our finding provides a novel conceptual approach to target barrier dysfunction and its resulting disorders with clinical/transitional importance.”

“Furthermore,” Zhang said, “in this research we showed that the effects of sEH are mediated by gut microbiota-dependent mechanisms. These research efforts could help to bridge two disparate fields, lipid signaling autacoids and gut microbiota, and hold great promise for success to create an important new research area.”

Corresponding author Hammock, a distinguished UC Davis professor who holds a joint appointment with the Department of Entomology and Nematology and the Comprehensive Cancer Center, praised Zhang's “amazing record while he was a postgraduate at UC Davis, and now in Food Science Department at the University of Massachusetts, where he recently received tenure.”

Zhang mentored two co-authors of the paper: Yuxin and Weicang Wang, both formerly of the Department of Food Science, University of Massachusetts and now with the Hammock lab.

“I feel so lucky that Yuxin and Weicang have joined my laboratory,” Hammock said. “The drugs studied in this PNAS paper are now in human clinical trials and on a path to replace opioid analgesics for pain treatment.  I hope the continuing work of Guodong, Weicang and Yuxin will evaluate them as treatments for a variety of inflammatory bowel diseases.”

Andreas Baumler, professor and vice chair of research in the UC Davis Department of Medical Microbiology and Immunology, who was not affiliated with the study, said: “Obesity-induced gut leakage and bacterial translocation can be ameliorated by targeting microbes with antibiotics, suggesting that the microbiota contributes to disease. However, the work by Zhang and co-workers suggest that rather than targeting the microbes themselves, obesity-induced gut leakage and bacterial translocation can be normalized by silencing a host enzyme, which identifies host metabolism as an alternative therapeutic target.”  

In addition to Hammock, Zhang, Yuxin and her husband Weicang, the other eight co-authors on the team are:

• Jun Yang, Sung Hee Hwang, and Debin Wan of the Hammock lab, UC Davis Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center
• Kin Sing Stephen Lee, formerly of the Hammock lab, and Maris Cinelli, both of the Department of Pharmacology and Toxicology, Michigan State University, Lansing
• Katherine Sanidad and Hang Xiao, Department of Food Science and the Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst
• Daeyoung Kim, Department of Mathematics and Statistics, University of Massachusetts, Amherst

The abstract: “Intestinal barrier dysfunction, which leads to translocation of bacteria or toxic bacterial products from the gut into bloodstream and results in systemic inflammation, is a key pathogenic factor in many human diseases. However, the molecular mechanisms leading to intestinal barrier defects are not well understood, and there are currently no available therapeutic approaches to target intestinal barrier function. Here we show that soluble epoxide hydrolase (sEH) is an endogenous regulator of obesity-induced intestinal barrier dysfunction. We find that sEH is overexpressed in the colons of obese mice. In addition, pharmacologic inhibition or genetic ablation of sEH abolishes obesity-induced gut leakage, translocation of endotoxin lipopolysaccharide or bacteria, and bacterial invasion-induced adipose inflammation. Furthermore, systematic treatment with sEH-produced lipid metabolites, dihydroxyeicosatrienoic acids, induces bacterial translocation and colonic inflammation in mice. The actions of sEH are mediated by gut bacteria-dependent mechanisms, since inhibition or genetic ablation of sEH fails to attenuate obesity-induced gut leakage and adipose inflammation in mice lacking gut bacteria. Overall, these results support that sEH is a potential therapeutic target for obesity-induced intestinal barrier dysfunction, and that sEH inhibitors, which have been evaluated in human clinical trials targeting other human disorders, could be promising agents for prevention and/or treatment.”

The research was funded by grants from the National Institute of Food and Agriculture, U.S. Department of Food and Agriculture (USDA); National Cancer Institute; USDA Hatch Grant; National Institute of Environmental Health Sciences (NIEHS) Superfund Research Program; and a National Science Foundation.

According to the CDC, many of obesity-related conditions that lead to diseases are preventable. In 2008, the estimated annual medical cost of obesity in the United States tallied $147 billion. The medical cost for obese individuals averaged $1,429 higher than those of normal weight.

Contact: Bruce Hammock, bdhammock@ucdavis.edu

Parents often try to predict the gender of their offspring, but is it possible to predict the sex of a cyst or sexually dimorphic nematode?

Yes, says plant nematologist Shahid Masood Siddique of the UC Davis Department of Entomology and Nematology,  who helped develop and validate a strategy to predict the sex of cyst nematodes (round worms) in roots of a mustard family plant in the early stages of infestation.

The research paper, "Host Factors Influence the Sex of Nematodes Parasitizing Roots of Arabidopsis thaliana," published in a recent edition of the journal Plant, Cell and Environment, zeroes in on nematodes parasitizing a small flowering plant widely used in plant biology and known as "mouse-ear cress." Arabidopsis is a member of the mustard (Brassicaceae) family, which includes cabbage and radish. A native of Eurasia and Africa, mouse-ear cress is found throughout much of the United States and Canada.

"We identified the host genes and factors that influence environmental sexual determination of plant parasitic nematodes," said Siddique, the senior author of the paper and an assistant professor at UC Davis. He played a key role in designing and performing the research well as the written work.

The seven-member team, led by Florian Grundler of the University of Bonn, Germany, found that the nematodes that developed at the fastest rate during the first four to 5 days became females, "whereas those that grew slower became mainly males."

"Interestingly, a study by Müller et al. (1981) on comparative food consumption by male and female juveniles from roots of Brassica napus found that females consume about 29 times more food than males," the researchers wrote. "Based on our data and previous literature, we concluded that the difference in food consumption leads to the difference in body volume between the sexes."

The team also included scientists from Germany, Poland, and Pakistan. A DAAD grant from Germany funded the research.

The abstract:

"Plant-parasitic cyst nematodes induce hypermetabolic syncytial nurse cells in the roots of their host plants. Syncytia are their only food source. Cyst nematodes are sexually dimorphic, with their differentiation into male or female strongly influenced by host environmental conditions. Under favourable conditions with plenty of nutrients, more females develop, whereas mainly male nematodes develop under adverse conditions such as in resistant plants. Here, we developed and validated a method to predict the sex of beet cyst nematode (Heterodera schachtii) during the early stages of its parasitism in the host plant Arabidopsis thaliana. We collected root segments containing male-associated syncytia (MAS) or female-associated syncytia (FAS), isolated syncytial cells by laser microdissection, and performed a comparative transcriptome analysis. Genes belonging to categories of defence, nutrient deficiency, and nutrient starvation were over-represented in MAS as compared with FAS. Conversely, gene categories related to metabolism, modification, and biosynthesis of cell walls were over-represented in FAS. We used β-glucuronidase analysis, qRT-PCR, and loss-of-function mutants to characterize FAS- and MAS-specific candidate genes. Our results demonstrate that various plant-based factors, including immune response, nutrient availability, and structural modifications, influence the sexual fate of the cyst nematodes."

Siddique, who joined the UC Davis faculty in March, focuses his research on basic as well as applied aspects of interaction between parasitic nematodes and their host plants. "The long-term object of our research is not only to enhance our understanding of molecular aspects of plant–nematode interaction but also to use this knowledge to provide new resources for reducing the impact of nematodes on crop plants in California."

Plant-parasitic nematodes are microscopic worms that extract water and nutrients from such host plants as wheat, soybeans, sugar beets and bananas. “They're one of the most destructive agricultural pests,” Siddique says. “The agricultural losses due to plant-parasitic nematodes reach an estimated $80 billion. The high impact of plant parasitic nematodes in economically important crops is not only due to the direct damage but also because of the role of some species as virus vectors.”

Related Link:

Meet Shahid Masood Siddique