Deeper understanding of how Yersinia plague pathogens impede the immune system could help investigators develop targeted treatments for these bacterial infections.
Investigators in Germany have advanced understanding of how Yersinia, the genus of bacteria that includes plague pathogens, work to impede the immune system.
Yersinia pathogens confuse the immune system by using a kind of syringe to insert enzymes, including YopO, into macrophages, where they change shape, binding to actin and preventing the phagocytes from absorbing the bacteria, according the study published in the journal Structure.
"Yersinia trick the macrophages of the immune system," Gregor Hagelüken, PhD, from the Institute of Physical and Theoretical Chemistry at the University of Bonn, said in a news release. By disrupting communication within the macrophages, the Yersinia remain “ultimately undisturbed.”
The research builds on previous work by investigators at Oxford University and the National University of Singapore who reported YopO bound to actin. The University of Bonn investigators wanted to create images of YopO, alone and as part of the YopO/actin complex, to better understand how the enzymes change shape.
"This idea was a challenge because the normal method of crystal structure analysis did not work with the free YopO. As it turns out, it is too flexible to form ordered crystals," lead author Martin F. Peter said in the news release.
Hagelüken, Peter, and colleagues, along with Dmitri Svergun from the European Molecular Biology Laboratory in Hamburg, turned to the PETRA III electron accelerator of the German Electron Synchrotron DESY. Investigators used pulsed electron double resonance (PELDOR) and small-angle X-ray scattering (SAXS) to study the transition and build models of the YopO/actin structure.
The enzyme transitions from a very flexible state to a much more rigid state. Its autophosphorylation is only activated in the presence of actin.
"Our results strongly indicate, however, that it is not a larger movement, but many small ones, with which YopO enters the active state," Peter said in the news release.
Better understanding of how pathogens trick the immune system may help develop targeted treatments in light of growing concern about antibiotic resistance.
Yersinia’s ability to obstruct the immune system has made it one of the most feared pathogens, responsible for devastating pandemics in history. Antibiotics have been successful in treating plague infections, but the disease has not been eradicated. It is found in rodents and transmitted mainly via fleas.
In May, the US Centers for Disease Control and Prevention listed the plague (Yersinia pestis) among the top 8 zoonotic diseases of most concern in the United States. Between 1978 and 1992, plague caused a total 1451 deaths in 21 countries, according to the World Health Organization.
Concerns about the plague were noted recently by Drew Pinsky, MD, who said it could be the next infectious disease threat in Los Angeles after the emergence of diseases including tuberculosis, measles, and typhus there. He attributed the re-emergence of so-called “medieval” diseases, in part, to the living conditions among the city’s growing homeless population.