Role of AlgC and GalU in the Intrinsic Antibiotic Resistance of

Overview

Journal Infect Drug Resist

Publisher Dove Medical Press

Date 2023 Apr 5

PMID 37016632

Authors

Shunhang Feng

Jiansheng Lin

Xiaoyan Zhang

Xin Hong

Wanyin Xu

Yancheng Wen

Feifei She

Affiliations

Soon will be listed here.

Abstract

Purpose: is associated with the development of gastrointestinal diseases. However, its eradication is challenged by an increased rate of drug resistance. AlgC and GalU are important for the synthesis of UDP-glucose, which is a substrate for the synthesis of lipopolysaccharide (LPS) in . In this study, we investigated the role of UDP-glucose in the intrinsic drug resistance in .

Methods: Gene knockout strains or complementation strains, including Δ, Δ, Δ, Δ, Δ/* and Δ/* were constructed in ; and Δ and Δ were also constructed in two clinical drug-resistant strains, and . The minimum inhibitory concentrations (MIC) of to amoxicillin (AMO), tetracycline (TET), clarithromycin (CLA), metronidazole (MNZ), levofloxacin (LEV), and rifampicin (RIF) were measured using MIC Test Strips. Silver staining was performed to examine the role of AlgC and GalU in LPS synthesis. Ethidium bromide (EB) accumulation assay was performed to assess the outer membrane permeability of strains.

Results: Knockout of and in resulted in increased drug sensitivity to AMO, MNZ, CLA, LEV, and RIF; whereas knockout of and , which are involved in GDP-fucose and UDP-galactose synthesis, respectively, did not significantly alter the drug sensitivity of . Knockout of and in clinically drug-resistant strains resulted in significantly increased drug sensitivity to all the antibiotics, except MNZ. The lipid A-core structure was altered in Δ and Δ when their EB accumulation was higher than that in the wild type and complementation strains.

Conclusion: UDP-glucose may play an important role in increasing drug resistance to AMO, MNZ, CLA, LEV, TET, and RIF by maintaining the lipid A-core structure and decreasing membrane permeability. AlgC and GalU may serve as potential drug targets for decreasing antibiotic resistance in clinical isolates.

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