Multitasking of Hsp70 chaperone in the biogenesis of bacterial functional amyloids

Abstract

Biofilms are intricate communities of microorganisms embedded in a self-produced matrix of extracellular polymer, which provides microbes survival advantages in stressful environments and can cause chronic infections in humans. Curli are functional amyloids that assemble on the extracellular surface of enteric bacteria such as Escherichia coli during biofilm development and colonization. The molecular chaperone DnaK, a bacterial Hsp70 homologue, promotes curli biogenesis via unknown mechanism(s). Here we show that DnaK increases the expression of CsgA and CsgB—the major and minor structural components of curli, respectively—via a quantity and quality control of RpoS, a stationary phase-specific alternative sigma factor regulating bacterial transcription, and CsgD, the master transcriptional regulator of curli formation. DnaK also keeps CsgA and CsgB in a translocation-competent state by binding to their signal peptides prone to aggregation. Our findings suggest that DnaK controls the homoeostasis of curli biogenesis at multiple stages to organize the biofilm matrix.

Decoding the proteomic changes involved in the biofilm formation of Enterococcus faecalis SK460 to elucidate potential biofilm determinants

“…Clp proteases involved in the degradation of misfolded proteins also showed elevated expression in biofilm stages. Several studies have proved the role of chaperone DnaK in curli-dependent biofilm formation and are considered as a potential target for anti-biofilm compounds [23–25].…”

The Hsp70-Chaperone Machines in Bacteria

“…Hsp70s are important for the insertion of tail-anchored proteins into the plasma membrane ( Peschke et al, 2018 ). Hsp70s prevent formation of amyloids in the cytoplasm and assist secretion of the functional amyloid curli that is necessary for biofilm formation and cell adhesion ( Evans et al, 2011 ; Sugimoto et al, 2018 ). Hsp70s are also involved in virulence of many pathogenic bacteria [for review see ( Ghazaei, 2017 )].…”

Transposon Insertion in the purL Gene Induces Biofilm Depletion in Escherichia coli ATCC 25922

“…Specifically, DnaK was involved in the transcriptional regulation of flhDC , responsible for the flagellum biogenesis, an important organelle associated with biofilm formation, adhesion, and colonisation [ 54 ]. Moreover, a recent work by Sugimoto et al [ 55 ] showed that the DnaK protein contributes to curli formation. Via rpoS , DnaK modulates the expression of the csgDEF operon which encodes for CsgD (master transcriptional regulator of curli) acting as a positive regulator of the csgBAC operon.…”