Identification of ClpB, a molecular chaperone involved in the stress tolerance and virulence of Streptococcus agalactiae

Vet Res. 2024 May 15;55(1):60. doi: 10.1186/s13567-024-01318-6.

Abstract

Bacterial ClpB is an ATP-dependent disaggregate that belongs to the Hsp100/Clp family and facilitates bacterial survival under hostile environmental conditions. Streptococcus agalactiae, which is regarded as the major bacterial pathogen of farmed Nile tilapia (Oreochromis niloticus), is known to cause high mortality and large economic losses. Here, we report a ClpB homologue of S. agalactiae and explore its functionality. S. agalactiae with a clpB deletion mutant (∆clpB) exhibited defective tolerance against heat and acidic stress, without affecting growth or morphology under optimal conditions. Moreover, the ΔclpB mutant exhibited reduced intracellular survival in RAW264.7 cells, diminished adherence to the brain cells of tilapia, increased sensitivity to leukocytes from the head kidney of tilapia and whole blood killing, and reduced mortality and bacterial loads in a tilapia infection assay. Furthermore, the reduced virulence of the ∆clpB mutant was investigated by transcriptome analysis, which revealed that deletion of clpB altered the expression levels of multiple genes that contribute to the stress response as well as certain metabolic pathways. Collectively, our findings demonstrated that ClpB, a molecular chaperone, plays critical roles in heat and acid stress resistance and virulence in S. agalactiae. This finding provides an enhanced understanding of the functionality of this ClpB homologue in gram-positive bacteria and the survival strategy of S. agalactiae against immune clearance during infection.

Keywords: Oreochromis niloticus; Streptococcus agalactiae; ClpB; stress tolerance; virulence.

MeSH terms

  • Animals
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Cichlids
  • Fish Diseases* / microbiology
  • Mice
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • RAW 264.7 Cells
  • Streptococcal Infections* / microbiology
  • Streptococcal Infections* / veterinary
  • Streptococcus agalactiae* / genetics
  • Streptococcus agalactiae* / pathogenicity
  • Streptococcus agalactiae* / physiology
  • Stress, Physiological*
  • Virulence