Glnk Mediates Carbapenem Resistance Through the NtrB/NtrC-OprD Regulatory Pathway in Pseudomonas aeruginosa

Sun, Xiaomeng; Li, Yiming; Gong, Xuetao; Du, Qitong; Jin, Yongxin; Cheng, Zhihui; Jin, Shouguang; Wu, Weihui

doi:10.3390/pathogens15030289

Open AccessArticle

Glnk Mediates Carbapenem Resistance Through the NtrB/NtrC-OprD Regulatory Pathway in Pseudomonas aeruginosa

by

Xiaomeng Sun

,

Yiming Li

,

Xuetao Gong

,

Qitong Du

,

Yongxin Jin

,

Zhihui Cheng

,

Shouguang Jin

and

Weihui Wu

^*

State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China

^*

Author to whom correspondence should be addressed.

Pathogens 2026, 15(3), 289; https://doi.org/10.3390/pathogens15030289

Submission received: 8 February 2026 / Revised: 4 March 2026 / Accepted: 4 March 2026 / Published: 6 March 2026

(This article belongs to the Special Issue Pathogenesis, Antibiotic Resistance, and Host Immune Responses to Bacterial Infections)

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Abstract

Pseudomonas aeruginosa is a major causative agent of nosocomial infections worldwide. Carbapenems are the first-line agents for combating severe P. aeruginosa infections. However, the increasing prevalence of carbapenem-resistant P. aeruginosa (CRPA) has developed as a critical threat to global healthcare systems. In this study, we demonstrated that a mutation in the core nitrogen metabolism regulatory gene glnK decreases carbapenem resistance in P. aeruginosa. OprD, the major porin for carbapenem uptake, is upregulated in the glnK mutant, resulting in decreased resistance. We further found that the NtrB/NtrC two-component regulatory system is upregulated in the glnK mutant. An electrophoretic mobility shift assay (EMSA) and genetic studies revealed a direct regulatory role of NtrC on the expression of oprD. Deletion of ntrB, ntrC, or oprD in the glnK mutant restored the bacterial resistance to carbapenems. These results reveal that a GlnK-NtrB/NtrC-OprD regulatory pathway affects carbapenem resistance, shedding light on the regulatory relationship between nitrogen metabolism and carbapenem resistance in P. aeruginosa.

Keywords: Pseudomonas aeruginosa; GlnK; NtrB/NtrC; oprD; carbapenem antibiotics

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MDPI and ACS Style

Sun, X.; Li, Y.; Gong, X.; Du, Q.; Jin, Y.; Cheng, Z.; Jin, S.; Wu, W. Glnk Mediates Carbapenem Resistance Through the NtrB/NtrC-OprD Regulatory Pathway in Pseudomonas aeruginosa. Pathogens 2026, 15, 289. https://doi.org/10.3390/pathogens15030289

AMA Style

Sun X, Li Y, Gong X, Du Q, Jin Y, Cheng Z, Jin S, Wu W. Glnk Mediates Carbapenem Resistance Through the NtrB/NtrC-OprD Regulatory Pathway in Pseudomonas aeruginosa. Pathogens. 2026; 15(3):289. https://doi.org/10.3390/pathogens15030289

Chicago/Turabian Style

Sun, Xiaomeng, Yiming Li, Xuetao Gong, Qitong Du, Yongxin Jin, Zhihui Cheng, Shouguang Jin, and Weihui Wu. 2026. "Glnk Mediates Carbapenem Resistance Through the NtrB/NtrC-OprD Regulatory Pathway in Pseudomonas aeruginosa" Pathogens 15, no. 3: 289. https://doi.org/10.3390/pathogens15030289

APA Style

Sun, X., Li, Y., Gong, X., Du, Q., Jin, Y., Cheng, Z., Jin, S., & Wu, W. (2026). Glnk Mediates Carbapenem Resistance Through the NtrB/NtrC-OprD Regulatory Pathway in Pseudomonas aeruginosa. Pathogens, 15(3), 289. https://doi.org/10.3390/pathogens15030289

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Glnk Mediates Carbapenem Resistance Through the NtrB/NtrC-OprD Regulatory Pathway in Pseudomonas aeruginosa

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