Mechanisms of tigecycline resistance in Gram-negative bacteria: A narrative review

Abstract

Tigecycline serves as a critical “final-resort” antibiotic for treating bacterial infections caused by multidrug-resistant bacteria for which treatment options are severely limited. The increasing prevalence of tigecycline resistance, particularly among Gram-negative bacteria, is a major concern. Various mechanisms have been identified as contributors to tigecycline resistance, including upregulation of nonspecific Resistance Nodulation Division (RND) efflux pumps due to mutations in transcriptional regulators, enzymatic modification of tigecycline by monooxygenase enzymes, and mutations affecting tigecycline binding sites. This review aims to consolidate our understanding of tigecycline resistance mechanisms in Gram-negative bacteria and offer insights and perspectives for further drug development.

Keywords

Gram-negative bacteria / Tigecycline / Tigecycline resistance / Resistance mechanisms / RND efflux pump

Funding

This work was supported by the National Key Research and De- velopment Program of China [grant number 2022YFE0199800], Key R&D Program of Shandong Province [grant number 2020CXGC011305], Shandong Provincial Natural Science Foundation [grant number ZR2020MH308], and the National Natural Science Foundation of China [grant number 82,271,658].

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

CRediT authorship contribution statement

Wenya Su: Writing - original draft, Visualization, Investigation. Wenjia Wang: Writing - review & editing, Investigation. Ling Li: Writing - review & editing, Investigation. Mengge Zhang: Writing - review & editing, Investigation. Hai Xu: Writing - review & editing, Conceptualization. Chengzhang Fu: Writing - review & editing. Xiuhua Pang: Writing - review & editing, Supervision, Project administration, Conceptualization. Mingyu Wang: Writing - review & editing, Visualization, Supervision, Project administration, Investigation, Funding acquisition, Conceptualization.

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