Targeting intracellular bacteria with antimicrobial virus-like particles: a case study with a single-cell resolution  

Abstract number
207
Presentation Form
Poster Flash Talk + Poster
Corresponding Email
[email protected]
Session
Stream 6 (Frontiers): Correlative Imaging of Organelle Organization and Architecture
Authors
Dr Stephanie Rey (1), Mrs Nilofar Faruqui (1), Dr Alex Hoose (1), Miss Camilla Dondi (1), Dr Maxim G Ryadnov (1)
Affiliations
1. National Physical Laboratory
Keywords

Electron microscopy, ultramicrotomy, antimicrobial peptides, intracellular bacteria


Abstract text

The emergence of multidrug-resistant bacteria stimulates the search for antimicrobial materials capable of addressing challenges conventional antibiotics fail to address. The ability to target intracellular bacteria remains one of the most fundamental tasks for contemporary antimicrobial treatments. Here we highlight our recent progress in demonstrating this ability for engineered protein virus-like particles targeting bacteria, which are internalised in macrophages. Using single-cell electron microscopy analysis we show that these materials effectively disrupt the bacteria without affecting the host cells. 

With better antibiotics inevitably leading to fitter intracellular pathogens, there is a pressing need for antimicrobial materials that may support mechanisms which are different from those of antibioticsThis study entails a promising discovery strategy by probing a principally more challenging strategy for bacteria to overcome – antibacterial virus-like forms that destroy bacteria on contact.


References

Azevedo, M., Sousa, A., Moura de Sousa, J., Thompson, J. A., Proença, J. T., Gordo, I. (2016) Trade-offs of Escherichia coli adaptation to an intracellular lifestyle in macrophages. PLoS ONE 11: e0146123.

Baker, S. J., Payne, D. J., Rappuoli, R., De Gregorio, E. (2018) Technologies to address antimicrobial resistance. Proc Natl Acad Sci USA 115: 12887-12895

Balaban, N. Q., Helaine, S., Lewis, K., Ackermann, M., Aldridge, B., Andersson, D. I., Brynildsen, M. P., Bumann, D., Camilli, A., Collins, J. J., et al. (2019) Definitions and guidelines for research on antibiotic persistence. Nat Rev Microbiol 17: 441-448 

Brauner, A., Fridman, O., Gefen, O., Balaban, N. Q. (2016) Distinguishing between resistance, tolerance and persistence to antibiotic treatment. Nat. Rev. Microbiol. 14: 320– 330

Castelletto, V., De Santis, E., Alkassem, H., Lamarre, B., Noble, J. E., Ray, S., Bella, A., Burns, J. R., Hoogenboom, B. W., Ryadnov, M. G. (2016) Structurally plastic peptide capsules for synthetic antimicrobial viruses. Chem Sci 7: 1707-1711

Czaplewski, L. et al. (2016) Alternatives to antibiotics-a pipeline portfolio review. Lancet Infect Dis. 16: 239-251

De Santis, E., Alkassem, H., Lamarre, B., Faruqui, N., Bella, A., Noble, J. E., Micale, N., Ray, S., Burns, J., Yon, A. R. et al. (2017) Antimicrobial peptide capsids of de novo design. Nat Commun 8: 2263

Hamill, K. M., McCoy, L. S., Wexselblatt, E., Esko, J. D., Tor, Y. (2016) Polymyxins facilitate entry into mammalian cells. Chem Sci 7: 5059-5068

Kepiro, I. E., Marzuoli, I., Hammond, K., Ba, X., Lewis, H., Shaw, M., Gunnoo, S. B., De Santis, E., Łapińska, U., Pagliara, S. et al. (2020) Engineering chirally blind protein pseudo-capsids into antibacterial persisters. ACS Nano 14: 1609-1622 

Poirier, K., Faucher, S. P., Béland, M., Brousseau, R., Gannon, V., Martin, C., Harel, J., Daigle, F. (2008) Escherichia coli O157:H7 survives within human macrophages: global gene expression profile and involvement of the Shiga toxins. Infect Immun 76: 4814–4822

Rakowska, P. D., Jiang, H., Ray, S., Pyne, A., Lamarre, B., Carr, M., Judge, P. J., Ravi, J., Gerling, U., Koksch, B. et al. (2013) Nanoscale imaging reveals laterally expanding antimicrobial pores in lipid bilayers. Proc Natl Acad Sci USA 110: 8918-8923

Rey, S., Faruqui, N., Ryadnov, M. G. (2021) Ultramicrotomy analysis of peptide treated cells. Methods Mol Biol 2208: 255-264

Sainsbury, F. (2020) Emergence by design in self-assembling protein shells. ACS Nano 14: 2565-2568

Schindler, P. R., Teuber, M. (1975) Action of polymyxin B on bacterial membranes: morphological changes in the cytoplasm and in the outer membrane of Salmonella Typhimurium and Escherichia Coli B. Antimicrob Agents Chemother 8: 95– 104

Sukumaran, S. K., Shimada, H., Prasadarao, N. V. (2003) Entry and intracellular replication of Escherichia coli K1 in macrophages require expression of outer membrane protein A. Infect Immun 71: 5951–5961

Zhang, Y. (2014) Persisters, persistent infections and the Yin-Yang model. Emerg Microbes Infect 3: e3