Distinct cell-types exist within genetically identical populations of bacteria
This holds true for many pathogens: Salmonella enterica, Neisseria gonorrhoeae, Yersina pseudoturberculosis, and Mycobacterium tuberculosis. In each of these cases, the emergence of these cell-types plays a critical role in disease or transmission.
These pathogens also lead to a wide-array of clinical manifestations during infection, from no symptoms to full-blown disease. By studying how these cell-types arise, function, and interact, we can better predict the factors that lead to serious illness and transmission.
Distinct cell-types emerge in populations of Salmonella cells
As Salmonella cells grow, virulent and avirulent cell types emerge. These two cell-types cooperate: virulent cells interact with host tissues and induce inflammation, while avirulent cells are fast-growing and remain unassociated with host tissues. The inflammation caused by the virulent cell-type enhances the growth of the avirulent type, ultimately sustaining infection.
These two cell-types are very likely distinct in ways other than virulence gene expression. The virulent cell-type grows is slow-growing, smaller, more resistant to antibiotics, has a higher proton-motive force, and responds differently to environmental stimuli. We are now working out these differences at a molecular level by combining single-cell transcriptomics and metabolomics to provide a systems-level view of Salmonella cell-types. The hope is to identify pathways specific to the virulent cell-type which could be targeted by therapeutics.
Supported by ETH SEED grant
Environmental conditions shape Salmonella cell-type behavior
By watching cells growing in a microfluidic device, we can examine how the environment impacts the behavior of individual cells. Here, we see the addition of short-chain fatty acids (SCFAs), compounds produced by gut microbes, stops cells from switching between avirulent (black) and virulent (green) types and causes virulent cells to grow more slowly.
