C910 chemical compound inhibits the traffiking of several bacterial AB toxins with cross-protection against influenza virus.
The development of anti-infectives against a large range of AB-like toxin-producing bacteria includes the identification of compounds disrupting toxin transport through both the endolysosomal and retrograde pathways. Here, we performed a high-throughput screening of compounds blocking Rac1 proteasomal degradation triggered by the Cytotoxic Necrotizing Factor-1 (CNF1) toxin, which was followed by orthogonal screens against two toxins that hijack the endolysosomal (diphtheria toxin) or retrograde (Shiga-like toxin 1) pathways to intoxicate cells. This led to the identification of the molecule C910 that induces the enlargement of EEA1-positive early endosomes associated with sorting defects of CNF1 and Shiga toxins to their trafficking pathways. C910 protects cells against eight bacterial AB toxins and the CNF1-mediated pathogenic Escherichia coli invasion. Interestingly, C910 reduces influenza A H1N1 and SARS-CoV-2 viral infection in vitro. Moreover, parenteral administration of C910 to mice resulted in its accumulation in lung tissues and a reduction in lethal influenza infection.
Pubmed ID: 35769882 RIS Download
Research resources used in this publication
Additional research tools detected in this publication
Antibodies used in this publication
- GAPDH Antibody (0411) (RRID:AB_627678)
- Polyclonal Swine Anti- Rabbit Immunoglobulins (RRID:AB_2617141)
- Goat Anti-Mouse Immunoglobulins/HRP (RRID:AB_2617137)
- Donkey Anti-Mouse IgG (H+L) Polyclonal Antibody, Alexa Fluor ?? 647 Conjugated (RRID:AB_162542)
- Donkey Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor ?? 488 Conjugated (RRID:AB_2535792)
- Donkey anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (RRID:AB_141607)
- Donkey Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor ?? 594 Conjugated (RRID:AB_141637)
- Donkey Anti-Mouse IgG (H+L) Antibody, Alexa Fluor ?? 594 Conjugated (RRID:AB_141633)
- Purified Mouse Anti-LBPA (BMP) (RRID:AB_11129226)
- Calnexin, pAb is associated with the following research areas: Innate Immunity, Endoplasmatic Reticulum Stress (RRID:AB_2038898)
- Rho A (26C4) (RRID:AB_628218)
- MEK-2 (N-20) (RRID:AB_2281672)
- TGN38 (21-G) (RRID:AB_1130226)
- Lamp-1 (RRID:AB_398356)
- Mouse Anti-Rab4 Monoclonal Antibody, Unconjugated, Clone 7 (RRID:AB_398205)
- Mouse Anti-Rac1 Monoclonal Antibody, Unconjugated, Clone 102 (RRID:AB_397978)
- Rab5 (RRID:AB_398047)
- EEA1 (RRID:AB_397830)
- 6x-His Tag Monoclonal Antibody (3D5) (RRID:AB_2556553)
- Mouse Anti-Giantin Monoclonal Antibody, Unconjugated, Clone 9B6 (RRID:AB_880195)
- Anti-RAB7 antibody [EPR7589] (ab137029) (RRID:AB_2629474)
- His-Tag (D3I1O) XP® (RRID:AB_2744546)
- Rabbit Anti-Rab7 XP??? Monoclonal Antibody, Unconjugated, Clone D95F2 (RRID:AB_1904103)
- Rabbit Anti-EEA1 Monoclonal Antibody, Unconjugated, Clone C45B10 (RRID:AB_2096811)
- Monoclonal Anti-β-Actin antibody produced in mouse (RRID:AB_476697)
Associated grants
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This is a list of tools and resources that we have found mentioned in this publication.
HUVEC-C (tool)
RRID:CVCL_2959
Cell line HUVEC-C is a Finite cell line with a species of origin Homo sapiens
View all literature mentionsHeLa (tool)
RRID:CVCL_0030
Cell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsVero (tool)
RRID:CVCL_0059
Cell line Vero is a Spontaneously immortalized cell line with a species of origin Chlorocebus sabaeus
View all literature mentionsVero C1008 (tool)
RRID:CVCL_0574
Cell line Vero C1008 is a Spontaneously immortalized cell line with a species of origin Chlorocebus sabaeus
View all literature mentionsGAPDH Antibody (0411) (antibody)
RRID:AB_627678
This monoclonal targets GAPDH
View all literature mentionsPolyclonal Swine Anti- Rabbit Immunoglobulins (antibody)
RRID:AB_2617141
This polyclonal targets Rabbit
View all literature mentionsGoat Anti-Mouse Immunoglobulins/HRP (antibody)
RRID:AB_2617137
This polyclonal targets Immunoglobulins
View all literature mentionsDonkey Anti-Mouse IgG (H+L) Polyclonal Antibody, Alexa Fluor ?? 647 Conjugated (antibody)
RRID:AB_162542
This polyclonal targets Mouse IgG (H+L)
View all literature mentionsDonkey Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor ?? 488 Conjugated (antibody)
RRID:AB_2535792
This unknown targets Rabbit IgG (H+L)
View all literature mentionsDonkey anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (antibody)
RRID:AB_141607
This polyclonal secondary targets IgG (H+L)
View all literature mentionsDonkey Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor ?? 594 Conjugated (antibody)
RRID:AB_141637
This unknown targets Rabbit IgG (H+L)
View all literature mentionsDonkey Anti-Mouse IgG (H+L) Antibody, Alexa Fluor ?? 594 Conjugated (antibody)
RRID:AB_141633
This unknown targets Mouse IgG (H+L)
View all literature mentionsPurified Mouse Anti-LBPA (BMP) (antibody)
RRID:AB_11129226
This unknown targets Purified Mouse LBPA (BMP)
View all literature mentionsCalnexin, pAb is associated with the following research areas: Innate Immunity, Endoplasmatic Reticulum Stress (antibody)
RRID:AB_2038898
This unknown targets Calnexin
View all literature mentionsTGN38 (21-G) (antibody)
RRID:AB_1130226
This monoclonal targets Human TGOLN2
View all literature mentionsMouse Anti-Rab4 Monoclonal Antibody, Unconjugated, Clone 7 (antibody)
RRID:AB_398205
This monoclonal targets Rab4
View all literature mentionsMouse Anti-Rac1 Monoclonal Antibody, Unconjugated, Clone 102 (antibody)
RRID:AB_397978
This monoclonal targets Rac1
View all literature mentions6x-His Tag Monoclonal Antibody (3D5) (antibody)
RRID:AB_2556553
This monoclonal targets 6x-His Tag
View all literature mentionsMouse Anti-Giantin Monoclonal Antibody, Unconjugated, Clone 9B6 (antibody)
RRID:AB_880195
This monoclonal targets Giantin
View all literature mentionsAnti-RAB7 antibody [EPR7589] (ab137029) (antibody)
RRID:AB_2629474
This monoclonal targets RAB7
View all literature mentionsHis-Tag (D3I1O) XP® (antibody)
RRID:AB_2744546
This monoclonal targets His-Tag
View all literature mentionsRabbit Anti-Rab7 XP??? Monoclonal Antibody, Unconjugated, Clone D95F2 (antibody)
RRID:AB_1904103
This monoclonal targets Rab7
View all literature mentionsRabbit Anti-EEA1 Monoclonal Antibody, Unconjugated, Clone C45B10 (antibody)
RRID:AB_2096811
This monoclonal targets EEA1
View all literature mentionsMonoclonal Anti-β-Actin antibody produced in mouse (antibody)
RRID:AB_476697
This monoclonal targets β-Actin
View all literature mentionsA-549 (cell line)
RRID:CVCL_0023
Cell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsC57BL/6J (organism)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentions
