Bacterial adhesion – MAM7
The initial binding of bacteria to host cells is crucial for the delivery of virulence factors and thus a key determinant for a pathogen’s success. We have recently discovered a multivalent adhesion molecule (MAM7) that enables a wide range of Gram-negative pathogens to establish high affinity binding to host cells during the early stages of infection. MAM7 binds to the host by engaging in both protein-protein (with fibronectin) and protein-lipid (with phosphatidic acid) interactions with the host cell membrane. MAM7 expression on the outer membrane of a Gram-negative pathogen is necessary for virulence in a nematode infection model and for efficient killing of cultured mammalian host cells. Expression of MAM7 on a non-pathogenic strain resulted in a tool that could be used to impede infection by Gram-negative bacterial pathogens. Targeting or exploiting MAM7 might provide a valuable tool for combating Gram-negative bacterial infections and we are currently exploring applications of MAM7 as an antimicrobial agent.
Cultured human cells infected with Yersinia pseudotuberculosis without (left) or with (right) protection of cells with non-pathogenic bacteria expressing MAM7. Pre-treatment with the competing strain inhibits cell killing by Yersinia.
Publications on bacterial adhesion
- Hawley, C.A., Watson, C., Orth, K. & Krachler, A-M. High-affinity binding of bacterial fibronectin-binding proteins to host cells inhibits critical steps in wound healing. PloS ONE (2013) 8.11:e81216
- Krachler, A-M. & Orth, K. Made to stick: Anti-adhesion therapy for bacterial infections as an alternative to conventional antimicrobials. (2013) Microbe 8:286-290.
- Krachler, A-M. & Orth, K. Targeting the bacteria-host interface: strategies in anti-adhesion therapy (2013) Virulence 4(4): 284-94.
- Krachler AM & Orth, K. In vitro characterization of Multivalent Adhesion Molecule 7-based inhibition of multidrug-resistant bacteria isolated from wounded military personnel. Virulence (2012) 3(4):389-99. PMC3478241
- Krachler, A-M, Ham, H. & Orth, K. Turnabout is fair play: Use of the bacterial Multivalent Adhesion Molecule 7 as an antimicrobial agent. Virulence (2012) 1;3(1).
- Krachler AM & Orth, K. Functional characterization of the interaction between bacterial adhesin multivalent adhesion molecule 7 (MAM7) protein and its host cell ligands. J Biol Chem. (2011) Nov 11;286(45):38939-47.
- Krachler AM, Ham H, Orth, K. The outer membrane adhesion factor MAM7 initiates host cell binding during infection with Gram-negative pathogens. (2011) Proc Natl Acad Sci USA. 108(28):11614-9. Highlighted in Nature and Nature Reviews Microbiology.