Metal chelation and inhibition of bacterial growth in tissue abscesses

Area of Science:

• Immunology
• Microbiology
• Biochemistry

Background:

• Bacterial infections commonly cause tissue abscesses, serving as key sites for host-pathogen interactions.
• The innate immune system's response within abscesses is crucial for infection control.

Purpose of the Study:

• To identify host factors within Staphylococcus aureus abscesses that influence bacterial growth.
• To investigate the role of the host protein calprotectin in the innate immune response to abscess formation.

Main Methods:

• Identification of host proteins within S. aureus abscesses.
• Assessment of calprotectin's effect on S. aureus growth in vitro and in vivo.
• Analysis of bacterial gene expression changes in response to calprotectin.
• Metal content analysis of abscesses in wild-type and calprotectin-deficient mice.

Main Results:

• Calprotectin, a neutrophil-dependent protein, is expressed within S. aureus abscesses.
• Neutrophil-derived calprotectin inhibits S. aureus growth by chelating manganese (Mn2+) and zinc (Zn2+).
• Calprotectin-mediated metal chelation leads to bacterial transcriptome reprogramming.
• Absences in calprotectin-deficient mice showed increased metal content and enhanced S. aureus proliferation.

Conclusions:

• Calprotectin is a critical innate immune factor active within abscesses.
• Metal chelation by calprotectin represents a significant antimicrobial strategy.
• Targeting metal availability is a potential therapeutic approach against abscess-forming bacterial infections.