EsxA is required for antibacterial toxin export by the type VIIb secretion system

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Molecular Biology

Background:

• Type VII secretion systems (T7SSb) are crucial in Bacillota for bacterial interactions and host modulation.
• These systems export effector proteins, including polymorphic LXG toxins, but the role of the conserved EsxA protein is unclear.
• The precise mechanism and hierarchy of substrate export by T7SSb remain largely unresolved.

Purpose of the Study:

• To elucidate the hierarchy and mechanistic basis of substrate export by the T7SSb of Streptococcus intermedius.
• To determine the relationship between EsxA secretion and LXG toxin export.
• To define the role of the EssC ATPase in substrate recognition and translocation.

Main Methods:

• Structural and mutational analyses of EsxA and LXG toxins.
• Biochemical assays to assess protein interactions and secretion dependency.
• Functional studies involving the EssC secretion ATPase domains.

Main Results:

• EsxA secretion is a prerequisite for LXG toxin export, demonstrating a unidirectional dependency.
• EsxA forms a homodimer with a bipartite export motif essential for its own secretion and LXG toxin export.
• Specific domains of the EssC ATPase are critical for substrate translocation and recognition, with EsxA export dependent on EssC compatibility.

Conclusions:

• EsxA acts as a conserved T7SSb substrate, essential for initiating the secretion cascade of LXG toxins.
• The findings reveal domain-specific requirements of EssC in substrate recognition and translocation, advancing our understanding of T7SSb mechanisms.
• This study establishes a clear hierarchy in T7SSb substrate export, with EsxA playing a pivotal role.