Staphylococcus aureus cell wall structure and dynamics during host-pathogen interaction

Area of Science:

• Microbiology
• Infectious Diseases
• Biochemistry

Background:

• Peptidoglycan is vital for Staphylococcus aureus cell wall integrity and antibiotic targeting.
• Understanding peptidoglycan dynamics during infection is crucial but poorly understood.

Purpose of the Study:

• To investigate Staphylococcus aureus cell wall structure and dynamics during active infection ex vivo.
• To determine the role of peptidoglycan homeostatic mechanisms, specifically PBP4 and glucosaminidases, in pathogenesis.

Main Methods:

• Developed methods to harvest bacteria from active infections for ex vivo cell wall analysis.
• Utilized genetic manipulation of Staphylococcus aureus (e.g., PBP4, SagB knockouts) and infection models (mice, zebrafish, macrophages).

Main Results:

• Ex vivo bacterial cells exhibit smaller size, thickened cell walls, and reduced peptidoglycan crosslinking compared to in vitro growth.
• Loss of PBP4 increased S. aureus recovery from mouse livers and enhanced survival in macrophages.
• Deficiency in SagB attenuated virulence in mice and reduced survival in human macrophages.
• Loss of Atl, SagA, and ScaH caused clustering-dependent attenuation in zebrafish embryos.

Conclusions:

• Appropriate cell wall structure and dynamics are critical for Staphylococcus aureus pathogenesis.
• PBP4 and SagB play significant roles in S. aureus virulence, representing potential therapeutic targets.