A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F20%3A00537471" target="_blank" >RIV/60077344:_____/20:00537471 - isvavai.cz</a>
Výsledek na webu
<a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009030" target="_blank" >https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009030</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1371/journal.ppat.1009030" target="_blank" >10.1371/journal.ppat.1009030</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis
Popis výsledku v původním jazyce
Lyme disease, the most common vector-borne illness in North America, is caused by the spirochete Borrelia burgdorferi. Infection begins in the skin following a tick bite and can spread to the hearts, joints, nervous system, and other organs. Diverse host responses influence the level of B. burgdorferi infection in mice and humans. Using a systems biology approach, we examined potential molecular interactions between human extracellular and secreted proteins and B. burgdorferi. A yeast display library expressing 1031 human extracellular proteins was probed against 36 isolates of B. burgdorferi sensu lato. We found that human Peptidoglycan Recognition Protein 1 (PGLYRP1) interacted with the vast majority of B. burgdorferi isolates. In subsequent experiments, we demonstrated that recombinant PGLYRP1 interacts with purified B. burgdorferi peptidoglycan and exhibits borreliacidal activity, suggesting that vertebrate hosts may use PGLYRP1 to identify B. burgdorferi. We examined B. burgdorferi infection in mice lacking PGLYRP1 and observed an increased spirochete burden in the heart and joints, along with splenomegaly. Mice lacking PGLYRP1 also showed signs of immune dysregulation, including lower serum IgG levels and higher levels of IFN gamma, CXCL9, and CXCL10.Taken together, our findings suggest that PGLYRP1 plays a role in the host's response to B. burgdorferi and further demonstrate the utility of expansive yeast display screening in capturing biologically relevant interactions between spirochetes and their hosts.
Název v anglickém jazyce
A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis
Popis výsledku anglicky
Lyme disease, the most common vector-borne illness in North America, is caused by the spirochete Borrelia burgdorferi. Infection begins in the skin following a tick bite and can spread to the hearts, joints, nervous system, and other organs. Diverse host responses influence the level of B. burgdorferi infection in mice and humans. Using a systems biology approach, we examined potential molecular interactions between human extracellular and secreted proteins and B. burgdorferi. A yeast display library expressing 1031 human extracellular proteins was probed against 36 isolates of B. burgdorferi sensu lato. We found that human Peptidoglycan Recognition Protein 1 (PGLYRP1) interacted with the vast majority of B. burgdorferi isolates. In subsequent experiments, we demonstrated that recombinant PGLYRP1 interacts with purified B. burgdorferi peptidoglycan and exhibits borreliacidal activity, suggesting that vertebrate hosts may use PGLYRP1 to identify B. burgdorferi. We examined B. burgdorferi infection in mice lacking PGLYRP1 and observed an increased spirochete burden in the heart and joints, along with splenomegaly. Mice lacking PGLYRP1 also showed signs of immune dysregulation, including lower serum IgG levels and higher levels of IFN gamma, CXCL9, and CXCL10.Taken together, our findings suggest that PGLYRP1 plays a role in the host's response to B. burgdorferi and further demonstrate the utility of expansive yeast display screening in capturing biologically relevant interactions between spirochetes and their hosts.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10606 - Microbiology
Návaznosti výsledku
Projekt
—
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
PLoS Pathogens
ISSN
1553-7374
e-ISSN
—
Svazek periodika
16
Číslo periodika v rámci svazku
11
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
21
Strana od-do
e1009030
Kód UT WoS článku
000592436400001
EID výsledku v databázi Scopus
2-s2.0-85096083410