Functional and Structural Diversity of Bacterial Contact-Dependent Growth Inhibition Effectors

Bonnie J Cuthbert; Christopher S Hayes; Celia W Goulding

doi:10.3389/fmolb.2022.866854

Functional and Structural Diversity of Bacterial Contact-Dependent Growth Inhibition Effectors

Front Mol Biosci. 2022 Apr 26:9:866854. doi: 10.3389/fmolb.2022.866854. eCollection 2022.

Authors

Bonnie J Cuthbert¹, Christopher S Hayes^{2

3}, Celia W Goulding^{1

4}

Affiliations

¹ Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, United States.
² Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, United States.
³ Biomolecular Science and Engineering Program, University of California, Santa Barbara, Santa Barbara, CA, United States.
⁴ Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, United States.

Abstract

Bacteria live in complex communities and environments, competing for space and nutrients. Within their niche habitats, bacteria have developed various inter-bacterial mechanisms to compete and communicate. One such mechanism is contact-dependent growth inhibition (CDI). CDI is found in many Gram-negative bacteria, including several pathogens. These CDI⁺ bacteria encode a CdiB/CdiA two-partner secretion system that delivers inhibitory toxins into neighboring cells upon contact. Toxin translocation results in the growth inhibition of closely related strains and provides a competitive advantage to the CDI⁺ bacteria. CdiB, an outer-membrane protein, secretes CdiA onto the surface of the CDI⁺ bacteria. When CdiA interacts with specific target-cell receptors, CdiA delivers its C-terminal toxin region (CdiA-CT) into the target-cell. CdiA-CT toxin proteins display a diverse range of toxic functions, such as DNase, RNase, or pore-forming toxin activity. CDI⁺ bacteria also encode an immunity protein, CdiI, that specifically binds and neutralizes its cognate CdiA-CT, protecting the CDI⁺ bacteria from auto-inhibition. In Gram-negative bacteria, toxin/immunity (CdiA-CT/CdiI) pairs have highly variable sequences and functions, with over 130 predicted divergent toxin/immunity complex families. In this review, we will discuss biochemical and structural advances made in the characterization of CDI. This review will focus on the diverse array of CDI toxin/immunity complex structures together with their distinct toxin functions. Additionally, we will discuss the most recent studies on target-cell recognition and toxin entry, along with the discovery of a new member of the CDI loci. Finally, we will offer insights into how these diverse toxin/immunity complexes could be harnessed to fight human diseases.

Keywords: contact-dependent growth inhibition; structure; toxin function; toxin/immunity complex; type V secretion system.

Publication types

Review

Abstract

Publication types

Grants and funding