Hot off the PRess
Perelman S, James D, Boguslawski K, Nelson C, Ilmain J, Zwack E, Prescott R, Mohamed A, Tam K, Chan R, Narechania A, Pawline M, Vozhilla N, Moustafa A, Kim SY, Dittmann M, Ekiert DC, Bhabha G, Shopsin B, Planet P, Koralov SB and Torres VJ.
In this study we set out to investigate the functional relevance of toxin variation in S. aureus. We analyze over 4,000 S. aureus genomes focusing on LukAB, a toxin responsible for S. aureus-mediated killing of primary human phagocytes. While the lukAB operon is found in all S. aureus clinical isolates, the toxin is highly divergent in amino acid sequence. We identified eight main LukAB lineages. We show that all the toxin variants are cytotoxic and that while the large majority of the LukAB variants require the host receptor CD11b to kill cells, the toxins produced by the CC30 & CC45 S. aureus lineages kill human phagocytes regardless of CD11b. We next performed a whole-genome CRISPR/Cas9 screen, which, together with functional studies, identified the Hydrogen Voltage Gated Channel 1 (HVCN1) as a novel host receptor for LukAB. The CC30 & CC45 LukAB variants target human, but not murine, HVCN1. By combining biochemical and cellular studies, we mapped the human LukAB-targeting domain of HVCN1 and then used this information together with CRISPR-Cas9 gene-editing to generate a novel humanized HVCN1 mouse (“hHVCN1”). Phagocytes from the hHVCN1 mice were found to be susceptible to LukAB-mediated cytotoxic activity, and compared to WT mice, the hHVCN1 mice exhibit increased susceptibility to bloodstream infection with S. aureus CC30 clinical isolates.
Fernandez J, Sanders H, Henn J, Wilson JM, Malone D, Buoninfante A, Willms M, Chan R, DuMont A, McLahan C, Grubb K, Romanello A, van den Dobbelsteen G, J T Poolman and Torres VJ and Poolman JT.
A novel deep surgical wound infection model in minipigs better mimics Staphylococcus aureus infection in humans and shows vaccination with a LukAB toxoid successfully mitigates S. aureus wound infections.
Vasquez MT, Lubkin A, Reyes-Robles T, Day CJ, Lacey KA, Jennings MP and Torres VJ.
A domain within the LukE subunit of the S. aureus toxin LukED targets the DARC receptor on red blood cells to promote hemolysis and is also important for targeting Darc in vivo.
Tam K, Lacey KA, Devlin JC, Coffre M, Sommerfield A, Chan R, O'Malley A, Koralov SB, Loke P and Torres VJ.
Leukocidins are secreted as immune evasion molecules, by vaccinating mice against the leukocidins, mice are protected from lethal S. aureus bacteremia.
Hernandez DN, Tam K, Shopsin B, Radke E, Law K, Cardozo T, Torres VJ, and Silverman GJ.
Phage display technology identified an immune dominant region of HlgC required for cytotoxicity from a panel of anti-HlgC monoclonal antibodies that is immunogenic in both humans and mice.
Devlin JC, Zwack EE, Tang MS, Li Z, Fenyo D, Torres VJ, Ruggles KV and Loke P.
The transcriptional responses of 4 different human myeloid cell types were defined to stimulation with a panel of cytokines and then applied the resulting gene signatures to assess the biological and clinical relevance of the different stimulated myeloid cells in the context of Tuberculosis and glioma.
Boguslawski KM, McKeown AN, Day CJ, Lacey KA, Tam K, Vozhilla N, Kim SY, Jennings MP, Koralov SB, Elde NC, and Torres VJ.
Development of a mouse expressing a humanized version of CD11b, the receptor for the human-specific S. aureus toxin LukAB, provides a much-needed model to study the role of this toxin in vivo.
Keller MD, Ching KL, Liang FX, Dhabaria A, Tam K, Ueberheide BM, Unutmaz D, Torres VJ, and Cadwell K.
Bacteria induce host cells to secrete exosomes containing bacterial toxin receptors, which serve as scavengers for bacterial toxins and provide protection from toxin-mediated cell death.
Keller MD, Torres VJ, Cadwell K.
Review on the role of autophagy proteins in host-microbe interactions and how cell biology informs pathogenicity studies involving of both viral and bacterial pathogens.
Hernandez DN, Tam K, Shopsin B, Radke E, Kolahi P, Copin R, Stubbe FX, Cardozo T, Torres VJ, and Silverman GJ.
An unbiased approach utilizing phage display to perform rapid screening of a recombinant antigen library against monoclonal antibodies identified a S. aureus leukotoxin epitope that is both cross-reactive and immunogenic.
Sause WE, Balasubramanian D, Irnov I, Copin R, Sullivan MJ, Sommerfield A, Chan R, Dhabaria A, Askenazi M, Ueberheide B, Shopsin B, van Bakel H, and Torres VJ.
The canonical metabolism regulator PurR can also influence S. aureus pathogenesis by directly regulating virulence genes.
Tam K, and Torres VJ.
Book chapter providing a brief overview of our current understanding of the major secreted virulence factors critical for S. aureus pathogenesis.
Lubkin A, Lee WL, Alonzo F 3rd, Wang C, Aligo J, Keller M, Girgis NM, Reyes-Robles T, Chan R, O'Malley A, Buckley P, Vozhilla N, Vasquez MT, Su J, Sugiyama M, Yeung ST, Coffre M, Bajwa S, Chen E, Martin P, Kim SY, Loomis C, Worthen GS, Shopsin B, Khanna KM, Weinstock D, Lynch AS, Koralov SB, Loke P, Cadwell K, Torres VJ.
S. aureus leukocidins target endothelial cells via DARC causing organ damage during bloodstream infection.
Chan R, Buckley PT, O'Malley A, Sause WE, Alonzo F 3rd, Lubkin A, Boguslawski KM, Payne A, Fernandez J, Strohl WR, Whitaker B, Lynch AS, Torres VJ.
Small protein biologics called centyrins can be engineered to combat the toxicity caused by systemic S. aureus infection.
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Sequential evolution of virulence and resistance during clonal spread of community-acquired methicillin-resistant Staphylococcus aureus.
Copin R, Sause WE, Fulmer Y, Balasubramanian D, Dyzenhaus S, Ahmed JM, Kumar K, Lees J, Stachel A, Fisher JC, Drlica K, Phillips M, Weiser JN, Planet PJ, Uhlemann AC, Altman DR, Sebra R, van Bakel H, Lighter J, Torres VJ, Shopsin B.
Rapid clonal spread of S. aureus within a high-risk community created intense selective pressure on the pathogen for increased virulence and antibiotic resistance.
Staphylococcus aureus Impairs the Function of and Kills Human Dendritic Cells via the LukAB Toxin.
Berends ETM, Zheng X, Zwack EE, Ménager MM, Cammer M, Shopsin B, Torres VJ.
Leukocidin AB hinders the adaptive immune response to S. aureus infection by killing dendritic cells (DCs) and impairing DC-mediated activation and proliferation of T cells.
Radke EE, Brown SM, Pelzek AJ, Fulmer Y, Hernandez DN, Torres VJ, Thomsen IP, Chiang WK, Miller AO, Shopsin B, Silverman GJ.
Characterization of the human serum IgG response to an array of S. aureus proteins reveals the predominant IgG response to S. aureus is to a subset of secreted factors, which is informative for better vaccine development.
Altman DR, Sullivan MJ, Chacko KI, Balasubramanian D, Pak TR, Sause WE, Kumar K, Sebra R, Deikus G, Attie O, Rose H, Lewis M, Fulmer Y, Bashir A, Kasarskis A, Schadt EE, Richardson AR, Torres VJ, Shopsin B, van Bakel H.
S. aureus strains deficient in the major virulence regulator agr acquire additional mutations to bypass the agr-defective mutation and promote virulence.
Congratulations to Daiane for receiving the Pew Latin American Fellowship!
Welcome Rotation Students: Alan & Teni!
Welcome Rotation Student: Xiao Ma!
Welcome Rotation Student: Julia Sproch!
Congratulations to Ashley on her promotion to Senior Research Scientist!
Welcome to the lab Daiane!
Welcome to the lab Amelia!
Welcome to the lab Andy!
Congratulations to Dr. Matthew Keller for successfully defending your thesis!
from the Torres Lab!
Dr. Kayan Tam on successfully defending your thesis!
Welcome to the lab Sandra!
Welcome to the lab Juliana, Exene, Rachel, Anna, and Krystal!
Dr. Kristina Boguslawski
on successfully defending your thesis!
Welcome Rotation Students
Exene Anderson and Krystal Ching!
Happy International Women in Science Day!
Victor Torres is now on Twitter!
Welcome Rotation Student Rachel Prescott!
The Torres Lab Survives 10 Years!
Congrats Victor on your "NYU Langone Outstanding Postdoc Mentor Award"!
Congrats to Dr. Ashira Lubkin on successfully defending your thesis!
Welcome Rotation Student Juliana Ilmain!