news-020216-bed-bug-genome (320x240)
Unfed bed bugs, Cimex lectularius. Image by Benoit Guenard.

In the dusk of impending night until just before the sun rises, they crawl onto the exposed skin of sleepers, injecting an anesthetic and a blood thinner before they suck the blood, rounding out their abdomens. As their unsuspecting victims slumber, they enjoy the only meal they really want – human blood. Bed bugs are the vampires of the insect world. While other insects, such as female mosquitoes, enjoy a sanguine meal, most eat other things as well. Bed bugs, however, prefer human blood, although they will eat from other mammals.

In a report that appears in the journal Nature Communications, an international consortium of scientists describe the sequence of the 650 megabase genome of the Cimex lectularius, the common bed bug. Within the code of the 14,200 genes that provide the blueprint for the workhorse proteins of the cell, they found genes linked to reproduction, the genes that attract the insects to human blood and several mechanisms that could lead to pesticide resistance.

After World War II, the pesticide DDT effectively eliminated bed bugs in most of the industrialized world. However, the past two decades has seen a resurgence of the blood sucking insects around the globe. This change has not been linked to dirtier homes but rather to international travel and growing resistance to pesticides in use since DDT was banned.

“There are consequences of the bed bugs’ vampire tendencies,” said Dr. Stephen Richards, associate professor in the Baylor College of Medicine Human Genome Sequencing Center. “Their blood meals make them swell up, and they have cuticle genes that give them the flexibility to do that. Blood is a liquid diet, and they have water channels that allow them to deal with the sheer amount of fluid. They have the olfactory and vision repertoire similar to other dawn-to-dusk insects.”

Even though bed bugs are not known to transmit disease, their bites can cause itchy welts. They can also live as long as a year without eating, said Richards.

“In practice, they are not a problem unless you have an infestation in your house,” he said.

“It’s no surprise we like to kill them,” said Richards. “However, that is becoming more difficult. We now have a list of all the genes that can be involved in resistance to pesticides.”

There are two types: those that attack nervous system ion channels and those such as cytochrome p450s that degrade prescription drugs in humans. When these are overexpressed or present at high levels, they can degrade pesticides.

“We provide the first full panel of all the potential genes that are likely involved with pesticide resistance,” said Dr. Joshua Benoit, an assistant professor of biological sciences at the University of Cincinnati and a lead author of the report. The report also provides full annotation of genes that make up the tough outer skeleton or cuticle of the bed bug, a source of pesticide resistance.

One unusual practice related to reproduction is traumatic insemination, said Dr. Kim Worley, professor in the Baylor Human Genome Sequencing Center.

“If a female mates with two males, how does the second male make sure the babies that result are his? In bed bugs, the male makes a hole in the female and injects the sperm through that. One gene family is involved in that. Then the sperm has to get to the egg.” There is no surety that the method works, she said.

“This genome serves as a beautiful gateway to future research on innovative ways to control bed bugs,” said Dr. Coby Shal, the Blanton J. Whitmire Distinguished Professor in the department of entomology at North Carolina State University and an author of the report. “Having all these genes sequenced is a goldmine for the academic setting and companies interested in controlling bed bugs, which are resistant to most of the chemicals we have.”

The other institutions that took part in the work include: Department of Biological Sciences, University of Cincinnati, Cincinnati, OH; University of Kentucky, Lexington, KY; Department of Entomology, Washington State University, Pullman, WA 99164; ICAR-National Bureau of Agricultural Insect Resources, Indian Council of Agricultural Research, Bengaluru 560024, India; Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Sciences Center, Memphis, TN; Fralin Life Science Institute and Department of Entomology, Virginia Tech, Blacksburg, VA; Cologne Biocenter and Zoological Institute, University of Cologne, 50674 Cologne, Germany; Institut für Bienenkunde (Polytechnische Gesellschaft), Goethe University Frankfurt, 61440 Oberursel, Germany; Department of Neurobiology and Genetics, Theodor-Boveri-Institute, Biocenter, University of Würzburg, 97074 Würzburg, Germany; Department of Biology, Applied Zoology, Technische Universität Dresden, 01062 Dresden, Germany; Department of Evolutionary Biology, Institute of Biology, Freie Universität, 14195 Berlin, Germany; Department of Genetic Medicine and Development and Swiss Institute of Bioinformatics, University of Geneva, Geneva 1211, Switzerland; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology and The Broad Institute of MIT and Harvard, Cambridge, MA; Pest Control Biology and Research Technologies, Bayer CropScience AG, 40789 Monheim, Germany; Department of Entomology, Texas A&M University, College Station, TX; Department of Entomology and W.M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC; Department of Entomology, Purdue University, West Lafayette, IN; Department of Entomology, University of Illinois at Urbana-Champaign, Urbana, IL; Department of Entomology and Nematology, University of Florida, Gainesville, FL; Institut de Génomique Fonctionnelle de Lyon (IGFL), Ecole Normale Supérieure de Lyon, UMR5242-CNRS, 69007 Lyon, France; Department of Entomology, Max Plank Institute for Chemical Ecology, 07745 Jena, Germany; National Agricultural Library, Beltsville, MD; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan; Department of Biochemistry and Genetics Otago, University of Otago, Dunedin 9054, New Zealand; Department of Biology, University of Rochester, Rochester, NY Institute of Fundamental Science, Massey University, Palmerston North 4442, New Zealand; Institute for Developmental Biology, University of Cologne, 50674 Cologne, Germany; Department of Biological Sciences, University of Tulsa, Tulsa, OK 74104; Department of Biological Sciences, Wayne State University, Detroit, MI; Center for Autoimmune Genomics and Etiology, Division of Biomedical Informatics, and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH; Department of Entomology, The Ohio State University, Wooster, OH; Department of Biological Chemistry and Crop Protection, Rothamsted Research, BBSRC Harpenden, Herts, AL5 2JQ, UK; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, Bethesda, MD; United States Department of Agriculture– Agricultural Research Service Bee Research Laboratory, Beltsville, Maryland; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, CT.

Funding for this work came from the National Human Genome Research Institute (Grant U54 HG0032730; the Blanton J. Whitmire Endowment, U.S. Department of Housing and Urban Development (Grant NCHHU-00017-13), National Science Foundation (IOS-1052238), Alfred P. Sloan Foundation (Grant 2013-5-35 MBE); the National Institutes of Health (Grant GM070559-9), the Royal Society of New Zealand Marsden Fast Start (Grant 11-UOO-124), Fralin Life Sciences Institutes and Virginia Agriculture Experimental Station, European Research Council (ERC-CoG 616346), Deutsche Forschungsgemeinschaft, Pe1798/2-1, Deutsche Forschungsgemeinschaft (DFG), collaborative research center SFB 1047 “Insect timing,” Project A1 to P.M., The Zukunftskonzept at TU Dresden funded by the Exzellenzinitiative of the Deutsche Forschungsgemeinschaft, Deutsche Forschungsgemeinschaft (DFG): BL469/7-1 to Wo.B., Deutsche Forschungsgemeinschaft, 766/11-1 , European Research Council Grant 260986, Biotechnology and Biological Sciences Research Council, University of Cincinnati Faculty Development Research Gran, Marie Curie International Outgoing Fellowship PIOF-GA-2011-303312, and Swiss National Science Foundation awards 31003A-125350 and 31003A-143936.