Host and vector adaptation in the tick-borne human pathogens Borrelia

• Applicant: Dr. Noémie Becker
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Evolution, Anthropology ; Microbial Ecology and Applied Microbiology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 393903649

• Final Report Year: 2024

Final Report Abstract

Lyme Borreliosis is a severe disease caused by bacteria belonging to the genus Borrelia. These bacteria are transmitted from host to host by ticks and their usual hosts are mainly rodents and birds. If not treated, infection in humans can establish in the skin, the joints or the nervous system of patients and lead to long-lasting symptoms. There are several Borrelia species and they differ by their geographical spread, by the hosts and vectors they can use and by the symptoms they most usually cause. Scientists can isolate the bacteria from ticks, hosts or patients, put them in culture and use their genomes to differentiate the species. Studying the adaptation of these bacteria to their natural hosts and vectors is very important to understand their evolution and, for example, why some Borrelia species able to infect humans and others not. Our project focused on three Borrelia species that are spread in Europe where they use the tick species Ixodes ricinus as vector and in Asia where the vector is Ixodes persulcatus. These three Borrelia species are adapted to different hosts: birds for Borrelia garinii and rodents for Borrelia bavariensis and Borrelia afzelii and all three can cause disease in humans. Our goal was to isolate these bacteria from ticks in Germany, Russia and Japan, sequence their genomes and use this data to understand how adaptation to the two different vectors and to the two types of hosts influenced the evolution of these bacteria. After collecting over 2,000 ticks, we produced over 180 new Borrelia isolates and studied their genome. Our most important finding was that all three Borrelia species had their origin in Asia in the tick Ixodes persulcatus. All three colonized Europe later by switching to the European tick Ixodes ricinus, but, surprisingly, the evolution leading to this adaptation followed completely different scenarios in the three species. In particular, the bird-adapted Borrelia garinii seems to be able to switch vector frequently, whereas the rodent-adapted species have much less migration between continents. We also used our new isolates to study specific genes that are linked to the evasion of the human immune system by Borrelia. We could show that these genes, belonging to the socalled PFam54 family, vary a lot between isolates. However, most studies of Borrelia use only a limited number of isolates and our results show that, by doing so, we might miss a lot of variation that might explain differences in human infection. We even identified two isolates that completely lack a full gene family that is thought to be necessary for human infection. However, these isolates come from patients and thus have been able to infect humans. This remains a puzzle but these two isolates will be further studied and can be used as a model to study the effect of these different genes. In conclusion, this research project showed that adapting to a new vector and colonizing a new continent can be done following several different evolutionary trajectories in Borrelia. We also showed that there is extraordinary genetic variation between isolates coming from the same locations which could contribute to this ability to adapt.

Publications

• High conservation combined with high plasticity: genomics and evolution of Borrelia bavariensis. BMC Genomics, 21(1).
  Becker, Noémie S.; Rollins, Robert E.; Nosenko, Kateryna; Paulus, Alexander; Martin, Samantha; Krebs, Stefan; Takano, Ai; Sato, Kozue; Kovalev, Sergey Y.; Kawabata, Hiroki; Fingerle, Volker & Margos, Gabriele
  
• Out of Asia? Vector switches leading to the expansion of Eurasian Lyme disease bacteria. Wiley.
  Rollins, Robert; Sato, Kozue; Nakao, Minoru; Tawfeeq, Mohammed; Herrera-Mesías, Fernanda; Pereira, Ricardo; Kovalev, Sergey; MARGOS, Gabriele; Fingerle, Volker; Kawabata, Hiroki & Becker, Noemie
  
• Spatial variability in prevalence and genospecies distributions of Borrelia burgdorferi sensu lato from ixodid ticks collected in southern Germany. Ticks and Tick-borne Diseases, 12(1), 101589.
  Rollins, Robert E.; Yeyin, Zehra; Wyczanska, Maja; Alig, Nikolas; Hepner, Sabrina; Fingerle, Volker; Margos, Gabriele & Becker, Noémie S.
  
• Ticks (Acari: Ixodidae) on birds migrating to the island of Ponza, Italy, and the tick-borne pathogens they carry. Ticks and Tick-borne Diseases, 12(1), 101590.
  Rollins, Robert E.; Schaper, Sabine; Kahlhofer, Claudia; Frangoulidis, Dimitrios; Strauß, Aurelia F.T.; Cardinale, Massimiliano; Springer, Andrea; Strube, Christina; Bakkes, Deon K.; Becker, Noémie S. & Chitimia-Dobler, Lidia
  
• Utilizing Two Borrelia bavariensis Isolates Naturally Lacking the PFam54 Gene Array To Elucidate the Roles of PFam54-Encoded Proteins. Applied and Environmental Microbiology, 88(5).
  Rollins, Robert E.; Wülbern, Janna; Röttgerding, Florian; Nowak, Tristan A.; Hepner, Sabrina; Fingerle, Volker; Margos, Gabriele; Lin, Yi-Pin; Kraiczy, Peter & Becker, Noémie S.