This is a close-up of Cimex lectularius, the common bed bug. A recently completed metagenomics study provides a rich genetic resource for mapping the pest’s activity and density across human hosts and cities, which can help track, manage, and control infestations. [Armed Forces Pest Management Bureau]
Although an old nursery rhyme tells us not to let the bed bugs bite, it neglects to say how we might protect ourselves. For that sort of information, we turn to science, which has been preoccupied of late with the question of how bed bug infestations keep getting worse. Most recently, science has been examining the bed bug at the genomic level. Here, the bed bug may harbor previously unknown vulnerabilities.
According to a new study led by researchers at the American Museum of Natural History and Weill Cornell Medicine, the newly sequenced bed bug genome could shed light on the bed bug’s basic biology and explain how the bed bug manages to adapt to dense human environments. This study may prove to be especially valuable because it is not limited to the basic genome. It takes in phylogenetic mapping, tracing bed bug activity in humans and their environments, including subway systems. The study also delves into the bed bug’s transcriptome and micobiome.
The researchers extracted DNA and RNA from preserved and living collections, including samples from a population that was first collected in 1973 and has been maintained by Museum staff members ever since. RNA was sampled from males and females representing each of the bug's six life stages, before and after blood meals, in order to paint a full picture of the bedbug genome.
“It's not enough to just sequence a genome, because by itself it does not tell the full story,” said Mark Siddall, Ph.D., one of the paper's corresponding authors and a curator in the Museum's Division of Invertebrate Zoology and Sackler Institute for Comparative Genomics. “In addition to the DNA, you want to get the RNA, or the expressed genes, and you want that not just from a single bedbug, but from both males and females at each part of the life cycle. Then you can really start asking questions about how certain genes relate to blood-feeding, insecticide resistance, and other vital functions.”
Details of the researchers’ work appeared February 2 in the journal Nature Communications, in an article entitled, “Genome assembly and geospatial phylogenomics of the bed bug Cimex lectularius.”
“Here we report the assembly, annotation, and phylogenetic mapping of the 697.9-Mb Cimex lectularius genome, with an N50 of 971 kb, using both long and short read technologies,” wrote the authors. “A RNA-seq time course across all five developmental stages and male and female adults generated 36,985 coding and noncoding gene models.”
The researchers found that the number of genes was fairly consistent throughout the bed bug life cycle, but they observed notable changes in gene expression, especially after the first blood meal. Some genes, expressed only after the bedbug first drinks blood, are linked to insecticide resistance, including mechanisms that result in better detoxification and thicker chitin, or skin.
This suggests that bedbugs are likely most vulnerable during the first nymph stage, potentially making it a good target for future insecticides. The scientists also identified three types of anticoagulant genes and their related proteins—characteristics consistent with a highly specialized blood feeder. When compared with 20 other arthropod genomes, the genome of the common bedbug shows a close relationship to the kissing bug (Rhodnius prolixus), one of several vectors for Chagas disease, and the body louse (Pediculus humanus), which both have tight associations with humans.
The bedbug microbiome also contains more than 1,500 genes that map to more than 400 different species of bacteria, indicating that bed bugs harbor a rich suite of endosymbionts that are likely essential for their growth and reproduction. This suggests that antibiotics that attack bacteria beneficial to bed bugs (but that are nonessential to humans) could complement control of the insects via pesticides.
“The most pronounced change in gene expression during the life cycle occurs after feeding on human blood and included genes from the Wolbachia endosymbiont, which shows a simultaneous and coordinated host/commensal response to hematophagous activity,” the authors noted. In his part of the sequencing project, 805 possible instances of genes being transferred from bacteria within the bed bug to the insect's chromosomes—a process called lateral gene transfer.
In addition, the study incorporated DNA data collected concurrently from more than 1,400 locations across New York City, including every subway station, to look at microbial diversity. For this work, the researchers used the new genomic data to focus exclusively on the diversity of bedbugs. They found differences in the genetic makeup of bedbugs that reside in different parts of the city, as measured by traces of DNA on east-west versus north-south subway lines, as well as between borough locations and among surfaces (for example, benches vs. turnstiles). The findings suggest that areas of the city in close proximity to each other have bedbug populations that are related, and that bedbugs from one borough can be distinct from those in another borough. This kind of information can be used to map the pathways of migration of bedbug infestations in established and new urban environments.
“A great feature of metagenomics and microbiome data is its power to reveal new biology, since you can map previously unknown sequences to a new genome as soon as it is finished,” said Christopher Mason, associate professor of computational genomics in the Department of Physiology and Biophysics and the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute for Computational Biomedicine at Weill Cornell Medicine and a senior author. “With every genome that is sequenced and annotated, the genetic understanding of the world around us becomes more in-focus.”