The Role of ClpB in Bacterial Stress Responses and Virulence

Abstract

Bacterial survival within a mammalian host is contingent upon sensing environmental perturbations and initiating an appropriate counter-response. To achieve this, sophisticated molecular machineries are used, where bacterial chaperone systems play key roles. The chaperones are a prerequisite for bacterial survival during normal physiological conditions as well as under stressful situations, e.g., infection or inflammation. Specific stress factors include, but are not limited to, high temperature, osmolarity, pH, reactive oxidative species, or bactericidal molecules. ClpB, a member of class 1 AAA⁺ proteins, is a key chaperone that via its disaggregase activity plays a crucial role for bacterial survival under various forms of stress, in particular heat shock. Recently, it has been reported that ClpB also regulates secretion of bacterial effector molecules related to type VI secretion systems. In this review, the roles of ClpB in stress responses and the mechanisms by which it promotes survival of pathogenic bacteria are discussed.

Keywords: ClpB chaperone; ClpB inhibitor; heat shock; stress response; type VI secretion.

FIGURE 1

A summary of ClpB’s so-far established roles in pathogenic bacteria, including T6S (Francisella only). Schematic figure illustrating the importance of ClpB in various stress responses, T6S and virulence. Model of the T6S in extended (left), contracted (central), and disassembled (right) forms of canonical and Francisella T6S is shown, where ClpB acts as an energizer. Canonical T6S subunits from Escherichia coli are labeled in black and Francisella T6S subunits, which are encoded within the Francisella Pathogenicity Island (FPI), are labeled in blue.