Structure insight into FtsZ function maintaining under acid stress of Streptococcus mutans

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Streptococcus mutans causes dental caries by resisting acidic environments.
• FtsZ protein is essential for bacterial cell division and its function under acid stress is not fully understood.
• Previous studies indicated enhanced FtsZ activity in S. mutans under acidic conditions.

Purpose of the Study:

• To elucidate the functional structure mechanism of S. mutans FtsZ (SmFtsZ) under low pH conditions.
• To investigate the role of a unique lateral interface in SmFtsZ function.
• To assess the potential of targeting SmFtsZ for inhibiting S. mutans growth.

Main Methods:

• Determined the crystal structure of S. mutans FtsZ.
• Performed protein polymerization and GTPase activity assays.
• Conducted phenotype assays and utilized a rat caries model.
• Employed molecular dynamics simulations.

Main Results:

• Identified a unique lateral interface in the SmFtsZ crystal structure.
• Demonstrated that mutating Arg68 on this interface significantly reduces SmFtsZ activity in acidic conditions.
• Showed that Arg68 mutation inhibits S. mutans acid resistance and reduces dental caries in vivo.
• Concluded that Arg68 mutation disrupts necessary conformational changes for SmFtsZ polymerization under acid stress.

Conclusions:

• Proposed a novel mechanism for maintaining bacterial FtsZ function under acidic stress.
• Identified Arg68 as a critical residue for SmFtsZ function in acid.
• Highlighted SmFtsZ as a potential antimicrobial drug target for inhibiting S. mutans in acidic environments.