TY - JOUR
T1 - PemB, a type III secretion effector in Pseudomonas aeruginosa, affects Caenorhabditis elegans life span
AU - Zelikman, Shira
AU - Dudkevich, Reut
AU - Korenfeld-Tzemach, Hadar
AU - Shmidov, Esther
AU - Levi-Ferber, Mor
AU - Shoshani, Sivan
AU - Ben-Aroya, Shay
AU - Henis-Korenblit, Sivan
AU - Banin, Ehud
N1 - Publisher Copyright:
© 2024
PY - 2024/4/30
Y1 - 2024/4/30
N2 - Pseudomonas aeruginosa is one of the leading nosocomial opportunistic pathogens causing acute and chronic infections. Among its main virulent factors is the Type III secretion system (T3SS) which enhances disease severity by delivering effectors to the host in a highly regulated manner. Despite its importance for virulence, only six T3SS-dependent effectors have been discovered so far. Previously, we identified two new potential effectors using a machine-learning algorithm approach. Here we demonstrate that one of these effectors, PemB, is indeed virulent. Using a live Caenorhabditis elegans infection model, we demonstrate this effector damages the integrity of the intestine barrier leading to the death of the host. Implementing a high-throughput assay using Saccharomyces cerevisiae, we identified several candidate proteins that interact with PemB. One of them, EFT1, has an ortholog in C. elegans (eef-2) and is also an essential gene and a well-known target utilized by different pathogens to induce toxicity to the worm. Accordingly, we found that by silencing the eef-2 gene in C. elegans, PemB could no longer induce its toxic effect. The current study further uncovers the complex machinery assisting P. aeruginosa virulence and may provide novel insight how to manage infection associated with this hard-to-treat pathogen.
AB - Pseudomonas aeruginosa is one of the leading nosocomial opportunistic pathogens causing acute and chronic infections. Among its main virulent factors is the Type III secretion system (T3SS) which enhances disease severity by delivering effectors to the host in a highly regulated manner. Despite its importance for virulence, only six T3SS-dependent effectors have been discovered so far. Previously, we identified two new potential effectors using a machine-learning algorithm approach. Here we demonstrate that one of these effectors, PemB, is indeed virulent. Using a live Caenorhabditis elegans infection model, we demonstrate this effector damages the integrity of the intestine barrier leading to the death of the host. Implementing a high-throughput assay using Saccharomyces cerevisiae, we identified several candidate proteins that interact with PemB. One of them, EFT1, has an ortholog in C. elegans (eef-2) and is also an essential gene and a well-known target utilized by different pathogens to induce toxicity to the worm. Accordingly, we found that by silencing the eef-2 gene in C. elegans, PemB could no longer induce its toxic effect. The current study further uncovers the complex machinery assisting P. aeruginosa virulence and may provide novel insight how to manage infection associated with this hard-to-treat pathogen.
KW - C. elegans
KW - Host
KW - Pathogen interaction
KW - PemB
KW - Pseudomonas aeruginosa
KW - Type III secretion system (T3SS)
KW - Virulence factors
UR - http://www.scopus.com/inward/record.url?scp=85190605649&partnerID=8YFLogxK
U2 - 10.1016/j.heliyon.2024.e29751
DO - 10.1016/j.heliyon.2024.e29751
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C2 - 38681583
AN - SCOPUS:85190605649
SN - 2405-8440
VL - 10
JO - Heliyon
JF - Heliyon
IS - 8
M1 - e29751
ER -