Saccharin disrupts bacterial cell envelope stability and interferes with DNA replication dynamics

Area of Science:

• Microbiology
• Biochemistry
• Antimicrobial Research

Background:

• Saccharin is a widely used artificial sweetener with known effects on the gut microbiome.
• The precise mechanisms by which saccharin affects bacteria remain largely unknown.

Purpose of the Study:

• To elucidate the mechanisms of saccharin's antimicrobial activity.
• To evaluate saccharin's potential as a broad-spectrum antimicrobial agent.

Main Methods:

• Investigated saccharin's effects on bacterial cell division, DNA synthesis, and cell envelope integrity.
• Assessed saccharin's impact on bacterial motility and biofilm formation.
• Tested saccharin's efficacy against established biofilms and its ability to re-sensitize multidrug-resistant bacteria to antibiotics.
• Incorporated saccharin into a hydrogel wound dressing for in vitro and ex vivo evaluation.

Main Results:

• Saccharin inhibits bacterial cell division, leading to filamentation and altered DNA synthesis.
• Cell lysis is triggered by bulges forming from the cell envelope.
• Saccharin inhibits growth of Gram-negative and Gram-positive bacteria, disrupting motility and biofilm formation.
• Saccharin effectively disrupts pre-formed biofilms and re-sensitizes multidrug-resistant pathogens to antibiotics.
• An effective hydrogel wound dressing incorporating saccharin was developed.

Conclusions:

• Saccharin exhibits multifaceted antimicrobial properties by targeting fundamental bacterial processes.
• Saccharin demonstrates significant potential as a versatile antimicrobial agent, including in wound care applications.