ClpB chaperone as a promising target for antimicrobial therapy: A narrative review

Abstract

The Clp/Hsp100 family, part of the ATPase associated with various cellular activities (AAA+) superfamily, includes caseinolytic peptidase B (ClpB), a highly conserved protein found in bacteria, fungi, protozoa, and plants. Notably, ClpB is present in all ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. ClpB plays a crucial role in reactivating and disaggregating proteins, enabling pathogens to survive under host-induced stress and conferring thermotolerance to bacterial cells. Infections caused by ESKAPE pathogens are particularly challenging due to their resistance to broad-spectrum antibiotics and biofilm formation, posing a significant global health threat as they are often multidrug-resistant, extensively drug-resistant, and pan-drug-resistant. Given its absence in human cells and its essential role in bacterial survival under stress, ClpB is a promising target for antimicrobial therapy. Targeting Hsp100 family proteins could lead to the development of novel antifungal and antiprotozoal treatments. This review explores the function of ClpB in the survival of ESKAPE pathogens and the protozoan Plasmodium falciparum. Relevant research findings were compiled using academic databases, and data analysis was performed using Clustal Omega Multiple Sequence Alignment and Boxshade tools.

Keywords

Molecular chaperone / ClpB / ESKAPE pathogens / Thermotolerance / Heat shock proteins / Plasmodium falciparum

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

The study received no extramural funding.

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

CBR conceptualized the framework of the review and supervised the project design along with RMN and UR. SJU and SS conducted the literature search, compiled studies for data acquisition, and prepared the initial draft. SJU and RMN created and refined the visual materials.

RMN, UR, NNS, and CBR handled the definition of intellectual content, provided insights, and verified references. NNS assessed data accuracy, provided feedback, and suggested additional literature. RMN, UR, and NNS guided the manuscript’s direction, ensuring scientific rigor and addressing key theoretical aspects.

CBR conducted the final critical revision of manuscript editing and review and approved the submission as the guarantor. All contributors aided in writing the manuscript, participated in discussions, and addressed reviewer comments.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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