In the 1960s, bed bugs seemed doomed. After centuries of living in the shadows and tormenting humanity, we were this close to eradicating them. Our main weapon was pesticides like DDT and pyrethroids, which proved devastatingly effective. But fast forward to today, and these tiny pests are back—stronger, smarter, and more resistant than ever before.
So what happened?
The resurgence of bed bugs has become a global headache as they infest homes, hotels, and public spaces. Recent research has revealed that bed bugs, Cimex lectularius, have evolved a series of sophisticated genetic defenses. These defenses make them almost invincible against the very chemicals that once seemed certain to drive them to extinction. But the authors of a new study sequenced the bugs’ genome, finding what they’re still vulnerable to.
Mutation and adaptation
The chemical assault on pests began in earnest after World War II. DDT (dichlorodiphenyltrichloroethane) and other synthetic pesticides were sprayed liberally in homes, hotels, and public buildings. Bed bugs, which feed on human blood and hide in cracks, seams, and mattresses, were vulnerable to these chemicals. For a brief period, the world experienced an almost bed bug-free era.
But that victory was short-lived. By the 1990s and 2000s, reports of bed bug infestations began to surge again. Hotels in major cities faced waves of complaints. This time, though, the bed bugs were different. Pesticides that had once worked wonders barely slowed them down.
“Bed bugs have expanded globally over the past two decades, causing several health risks. Mutations in their genes allow bed bugs to develop insecticide resistance,” write the authors of a new study published in the journal Insects. The researchers, led by Hidemasa Bono of Hiroshima University, sequenced the genomes of bed bugs that are both susceptible and resistant to pesticides.
The researchers found hundreds of gene mutations specific to the resistant bed bugs. These mutations weren’t random. They offered resistance to pyrethroids—the most commonly used pesticide against bed bugs today.
Annoying bugs
Bed bugs are micropredators that feed on blood, usually at night. They don’t really pass any diseases to humans, but their bite can cause rashes, blisters, and allergic reactions.
What we call “bed bugs” are actually two species: Cimex lectularius (the common bed bug) and Cimex hemipterus, found primarily in the tropics. They’ve been with us for thousands of years. We have found bed bug fossils in Egypt dating to over 3,500 years ago.
In the past years, they’ve gotten so resistant to pesticides that experts typically recommend non-chemical control methods. In other words, the best way to get rid of bed bugs is to vacuum and throw them away. The next best thing is to remove all fabrics and wash them at over 60 degrees Celsius. There’s no evidence that a combination of non-chemical methods plus insecticides is more effective than non-chemical methods alone.
Resistance didn’t happen overnight. It evolved over decades, driven by the inefficient use of pesticides. Sometimes, a bed bug population was exposed to pesticides but some individuals survived. These survivors reproduced, passing their resilient genes to the next generation. Repeated exposure to pesticides acted as a filter, allowing only the toughest bed bugs to thrive. Eventually, resistant strains dominated the population. This process, known as “selective pressure,” is a textbook example of evolution in action.
“We determined the genome sequence of insecticide-resistant bed bugs, which exhibited 20,000-fold greater resistance compared to susceptible bed bugs. By comparing the amino acid sequences between the susceptible and resistant bed bugs, we identified 729 transcripts with resistance-specific mutations,” said study first author Kouhei Toga, postdoctoral researcher at the Laboratory of Genome Informatics of HU’s Graduate School of Integrated Sciences for Life.
So what changed?
Sequencing a genome is a bit like assembling a massive jigsaw puzzle, often with millions and millions of pieces. The key breakthrough in this case was the method of long-read sequencing, which can sequence long strands of DNA or RNA in one go, without breaking it up into smaller fragments.
They ended up with a near-total picture of the two genomes (of resistant and non-resistant bugs), achieving completeness of around 98% for the former and 95% for the latter.
One key finding was the role of voltage-gated sodium channels. These channels are critical for nerve function, and pyrethroids work by disrupting them, causing paralysis and death. However, resistant bed bugs had mutations in these sodium channels, making them less vulnerable to the pesticide’s effects. Essentially, the pesticide couldn’t “lock” onto its target anymore.
In addition to sodium channels, the study identified changes in genes related to other defense mechanisms. Some mutations enhanced the bed bugs’ ability to metabolize (and detoxify) the chemicals faster. Others thickened their exoskeleton, preventing pesticides from penetrating their bodies. Together, these adaptations formed a formidable shield against chemical attacks.
Some bed bugs had mutations in genes associated with acetylcholinesterase, an enzyme targeted by organophosphate and carbamate pesticides. These mutations further expanded the bed bugs’ arsenal against different classes of chemicals.
“We identified a large number of genes likely involved in insecticide resistance, many of which have not been previously reported as being associated with resistance in bedbugs. Genome editing of these genes could provide valuable insights into the evolution and mechanisms of insecticide resistance,” Toga said. The study also highlighted more genes than we previously knew to monitor in bed bug populations.
Ultimately, the hope is that this study can help us develop more efficient pesticides by pinpointing the exact genetic mutations that confer resistance in bed bugs. By identifying the specific changes in genes related to sodium channels, metabolism, and detoxification, scientists can design new pesticides that bypass these defenses or target different biological pathways.
The study was published in the journal Insects.
