Activation of the ChvG-ChvI pathway promotes multiple survival strategies during cell wall stress in Agrobacterium tumefaciens

Bouchier, J. M.; Knebel, E.; Amstutz, J.; Torrens, G.; Santiago-Collazo, G.; McCurry, C.; Weisburg, A. J.; Cava, F.; Brown, P. J.

doi:10.1101/2024.12.10.627833

bioRxiv · 10.1101/2024.12.10.627833

Activation of the ChvG-ChvI pathway promotes multiple survival strategies during cell wall stress in Agrobacterium tumefaciens

Bouchier, J. M.·Knebel, E.·Amstutz, J.·Torrens, G.·Santiago-Collazo, G.·McCurry, C.·Weisburg, A. J.·Cava, F.·Brown, P. J.

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Abstract

Agrobacterium tumefaciens shifts from a free-living soil bacterium to a plant-invading state upon encountering the plant root microenvironment. The acid-induced two- component sensor system ChvG-ChvI drives this shift and triggers a complex transcriptional program that promotes host invasion and survival against host immune defenses. Remarkably, ChvG-ChvI is also activated under cell wall stress conditions suggesting that the transcriptional response may have a broader function. Here, we find that blocking cell wall synthesis either genetically or chemically leads to ChvG-ChvI activation. Mutations in key cell wall synthesis or outer membrane proteins, such as PBP1a, FtsW, and AopA1, suppress ChvG-ChvI activation suggesting that providing structural integrity is a primary function of the ChvG-ChvI regulon. Here, we investigated regulon components for this function. First, the exopolysaccharide succinoglycan confers tolerance to multiple {beta}-lactam antibiotics targeting different enzymes by forming a protective barrier around the cells. Next, a Class D {beta}-lactamase is expressed which may contribute to the high level of {beta}-lactam resistance in A. tumefaciens. Finally, outer membrane remodeling compensates for the accumulation of cell wall damage by providing structural integrity. Overall, we expand our understanding of mechanisms driving ChvG-ChvI activation and {beta}-lactam resistance in a bacterial plant pathogen. Significance Statements.O_LIActivation of the ChvG-ChvI two component system promotes survival when the bacterial cell walls are damaged by a variety of genetic or chemical approaches C_LIO_LIThe ChvG-ChvI dependent production of the exopolysaccharide succinoglycan, {beta}-lactamase Cbl activity, and outer membrane proteome remodeling all contribute to survival in the presence of {beta}-lactam antibiotics C_LIO_LIImproved understanding of bacterial stress responses that promote antibiotic tolerance and resistance has the potential to inform development of novel drug targets C_LI

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Bouchier, J. M., Knebel, E., Amstutz, J., Torrens, G., Santiago-Collazo, G., McCurry, C., Weisburg, A. J., Cava, F., Brown, P. J.. 2024-12-11. Activation of the ChvG-ChvI pathway promotes multiple survival strategies during cell wall stress in Agrobacterium tumefaciens. https://doi.org/10.1101/2024.12.10.627833

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