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A Potent Anti-SpuE Antibody Allosterically Inhibits Type III Secretion System and Attenuates Virulence of Pseudomonas Aeruginosa.

Zhang Y, Sun X, Qian Y, Yi H, Song K, Zhu H, Zonta F, Chen W, Ji Q, Miersch S, Sidhu SS, Wu D
J Mol Biol 431 4882-4896 (2019)
Cited: 9 times
EuropePMC logo PMID: 31682834

Abstract

Multidrug-resistant gram-negative bacteria infection is particularly severe within the designated ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), which underscores the urgent need to explore alternative therapeutic strategies. The type III secretion system (T3SS) is considered to be a key virulence factor in many gram-negative bacteria, and T3SS is in turn regulated by SpuE in P. aeruginosa, which is a spermidine binding protein from an ATP-binding cassette transporter family and highly conserved within ESKAPE pathogens. Here, we identified a potent anti-SpuE antagonistic antibody that allosterically inhibits the expression of T3SS and attenuates virulence of P. aeruginosa. X-ray crystallography and molecular dynamics simulations revealed that binding of antibody to SpuE induces a change in the dynamics of SpuE, which in turn may reduce spermidine uptake by P. aeruginosa. The antibody could serve as a template for developing novel biologics to target a broad spectrum of gram-negative bacteria.

Reviews citing this publication (5)

  1. Developing Recombinant Antibodies by Phage Display Against Infectious Diseases and Toxins for Diagnostics and Therapy. Roth KDR, Wenzel EV, Ruschig M, Steinke S, Langreder N, Heine PA, Schneider KT, Ballmann R, Fühner V, Kuhn P, Schirrmann T, Frenzel A, Dübel S, Schubert M, Moreira GMSG, Bertoglio F, Russo G, Hust M. Front Cell Infect Microbiol 11 697876 (2021)
  2. Antibodies Inhibiting the Type III Secretion System of Gram-Negative Pathogenic Bacteria. Hotinger JA, May AE. Antibodies (Basel) 9 E35 (2020)
  3. Acinetobacter Baumannii Phages: Past, Present and Future. Tu Q, Pu M, Li Y, Wang Y, Li M, Song L, Li M, An X, Fan H, Tong Y. Viruses 15 673 (2023)
  4. Phage Display-Derived Peptides and Antibodies for Bacterial Infectious Diseases Therapy and Diagnosis. Zhao H, Nie D, Hu Y, Chen Z, Hou Z, Li M, Xue X. Molecules 28 2621 (2023)
  5. Vaccines and Monoclonal Antibodies as Alternative Strategies to Antibiotics to Fight Antimicrobial Resistance. La Guidara C, Adamo R, Sala C, Micoli F. Int J Mol Sci 25 5487 (2024)

Articles citing this publication (4)



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