The CdbS PilZ domain protein, together with two PilZ-DnaK proteins, perturbs chromosome organization and accelerates cell death during heat stress in Myxococcus xanthus

ABSTRACT: C-di-GMP is a bacterial second messenger that regulates diverse processes in response to environmental or cellular cues. The nucleoid-associated protein (NAP) CdbA in Myxococcus xanthus binds DNA and c-di-GMP in a mutually exclusive manner in vitro. CdbA is essential for viability, and CdbA depletion causes defects in chromosome organization, leading to a block in cell division and, ultimately, cell death. Most NAPs are not essential; therefore, to explore the paradoxical cdbA essentiality, we isolated suppressor mutations that restored cell viability without CdbA. Most mutations mapped to cdbS, which encodes a stand-alone c-di-GMP binding PilZ domain protein, and caused loss-of-function of cdbS. Cells lacking CdbA and CdbS or only CdbS were fully viable and had no defects in chromosome organization. CdbA depletion caused post-transcriptional upregulation of CdbS accumulation, and this CdbS over-accumulation was required and sufficient to disrupt chromosome organization and, ultimately, cause cell death. CdbA depletion also caused increased accumulation of CsdK1 and CsdK2, two unusual PilZ-DnaK chaperones. During CdbA depletion, CsdK1 and CsdK2, in turn, stabilized CdbS, thereby enabling its increased accumulation and toxicity. CdbS accumulation also increased in response to heat stress at 37°C in a CsdK1- and CsdK2-dependent manner, possibly also involving an increased cellular c-di-GMP concentration, causing disrupted chromosome organization and accelerated cell death. Thus, increased CdbS accumulation caused by either CdbA depletion or heat stress results in disrupted chromosome organization and cell death. Collectively, our results suggest that the CdbA/CsdK1/CsdK2/CdbS system represents a new system for regulated cell death.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Myxococcus Xanthus Dk 1622

SUBMITTER: Timo Glatter  

LAB HEAD: Timo Glatter

PROVIDER: PXD041344 | Pride | 2023-05-24

REPOSITORIES: Pride