New Protein Targets Support Diagnostics for Louse-Borne Relapsing Fever

Louse-borne relapsing fever is a neglected infection caused by Borrelia recurrentis and spread by body lice, with untreated mortality reaching up to 20%. Recurrent febrile episodes complicate recognition and triage, and sporadic outbreaks persist in parts of the Horn of Africa. How the pathogen persists in the human host has been unclear, hindering targeted diagnostics. Researchers have now identified outer surface proteins that drive immune evasion and form the basis for new serological tests.

At Goethe University Frankfurt and Universitätsmedizin Frankfurt, investigators identified and characterized five closely related outer surface proteins in B. recurrentis, termed Chi proteins, that are critical for survival in humans. Working with Justus Liebig University Giessen, the team showed the proteins share a common ancestry and functional profile. The work delineates how the organism withstands first-line host defenses during bloodstream infection.

The Chi proteins bind specific blood proteins to suppress activation of the human complement system, a central arm of innate immunity that tags and eliminates bacteria. By blocking complement-mediated opsonization, they prevent immune recognition and clearance. The proteins also capture plasminogen and convert it into active plasmin, facilitating tissue invasion after entry into the host.

The findings were published in Nature Communications. Louse-borne relapsing fever, transmitted by body lice, is classified as a poverty-related neglected disease and can be fatal in up to 20% of untreated cases. Sporadic outbreaks are reported in countries around the Horn of Africa, and rising case detection among refugees drew attention in Europe in 2015, although individual studies indicate European body lice currently do not carry the pathogen.

Building on these results, the researchers have developed diagnostic tests and are conducting serological studies in Kenya and Nigeria. The proteins may also represent candidates for vaccine development. Targeted assays for fever of unknown origin could enable timely, pathogen-specific antibiotic therapy, and preparedness remains important despite the current absence of infected body lice in Europe.

"We know from other pathogens that they use the body's own plasmin to invade tissues. Together with the ability of the Chi proteins to block the complement system, this gives Borrelia recurrentis significant advantages in surviving and spreading after entering the human body," said Peter Kraiczy, head of the Borrelia research group at the Institute of Medical Microbiology and Infection Control at Universitätsmedizin Frankfurt and Goethe University.

"Fever of unknown origin occurs in many infectious diseases, so pathogen-specific tests make it possible to quickly initiate the appropriate antibiotic treatment against the causative agent. We have already made considerable progress in this area and are currently conducting studies in Kenya and Nigeria using serological tests developed in our laboratory," added Peter Kraiczy.

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Goethe University Frankfurt 
Universitätsmedizin Frankfurt
Justus Liebig University Giessen