The Burkholderia pseudomallei intracellular ‘TRANSITome’

Yun Heacock-Kang, Ian A. McMillan, Michael H. Norris, Zhenxin Sun, Jan Zarzycki-Siek, Andrew P. Bluhm, Darlene Cabanas, Robert E. Norton, Natkunam Ketheesan, Jeff F. Miller, Herbert P. Schweizer and Tung T. Hoang ()
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Yun Heacock-Kang: University of Hawaiʻi at Mānoa
Ian A. McMillan: University of Hawaiʻi at Mānoa
Michael H. Norris: University of Hawaiʻi at Mānoa
Zhenxin Sun: University of Hawaiʻi at Mānoa
Jan Zarzycki-Siek: University of Hawaiʻi at Mānoa
Andrew P. Bluhm: University of Hawaiʻi at Mānoa
Darlene Cabanas: University of Hawaiʻi at Mānoa
Robert E. Norton: Townsville Hospital
Natkunam Ketheesan: University of New England
Jeff F. Miller: University of California
Herbert P. Schweizer: Northern Arizona University
Tung T. Hoang: University of Hawaiʻi at Mānoa

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Prokaryotic cell transcriptomics has been limited to mixed or sub-population dynamics and individual cells within heterogeneous populations, which has hampered further understanding of spatiotemporal and stage-specific processes of prokaryotic cells within complex environments. Here we develop a ‘TRANSITomic’ approach to profile transcriptomes of single Burkholderia pseudomallei cells as they transit through host cell infection at defined stages, yielding pathophysiological insights. We find that B. pseudomallei transits through host cells during infection in three observable stages: vacuole entry; cytoplasmic escape and replication; and membrane protrusion, promoting cell-to-cell spread. The B. pseudomallei ‘TRANSITome’ reveals dynamic gene-expression flux during transit in host cells and identifies genes that are required for pathogenesis. We find several hypothetical proteins and assign them to virulence mechanisms, including attachment, cytoskeletal modulation, and autophagy evasion. The B. pseudomallei ‘TRANSITome’ provides prokaryotic single-cell transcriptomics information enabling high-resolution understanding of host-pathogen interactions.

Date: 2021
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DOI: 10.1038/s41467-021-22169-1

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