Faculty Collaboration Database

Mutually constructive roles of Ail and LPS in Yersinia pestis serum survival. Mol Microbiol 2020 Sep;114(3):510-520

Date

05/29/2020

Pubmed ID

32462782

Pubmed Central ID

PMC7594906

DOI

10.1111/mmi.14530

Scopus ID

2-s2.0-85087207600 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

The outer membrane is a key virulence determinant of gram-negative bacteria. In Yersinia pestis, the deadly agent that causes plague, the protein Ail and lipopolysaccharide (LPS)⁶ enhance lethality by promoting resistance to human innate immunity and antibiotics, enabling bacteria to proliferate in the human host. Their functions are highly coordinated. Here we describe how they cooperate to promote pathogenesis. Using a multidisciplinary approach, we identify mutually constructive interactions between Ail and LPS that produce an extended conformation of Ail at the membrane surface, cause thickening and rigidification of the LPS membrane, and collectively promote Y. pestis survival in human serum, antibiotic resistance, and cell envelope integrity. The results highlight the importance of the Ail-LPS assembly as an organized whole, rather than its individual components, and provide a handle for targeting Y. pestis pathogenesis.

Author List

Singh C, Lee H, Tian Y, Schesser Bartra S, Hower S, Fujimoto LM, Yao Y, Ivanov SA, Shaikhutdinova RZ, Anisimov AP, Plano GV, Im W, Marassi FM

Author

Francesca M. Marassi PhD Chair, Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Motifs
Anti-Bacterial Agents
Bacterial Outer Membrane Proteins
Drug Resistance, Bacterial
Humans
Lipopolysaccharides
Microbial Sensitivity Tests
Molecular Dynamics Simulation
Mutation
Plague
Protein Binding
Protein Conformation
Virulence Factors
Yersinia pestis