On January 3, 2022, Professor Gu Bing's team from the Clinical Laboratory Department of Guangdong Provincial People's Hospital and Professor Wang Chengbin's team from the Chinese PLA General Hospital published an article entitled “Proteomic and Transcriptomic Analyses Indicate Reduced Biofilm-Forming Abilities in Cefiderocol-Resistant Klebsiella pneumoniae” (DOI: 10.3389 / fmicb. 2021.778190) in Frontiers in Microbiology.

The paper used proteomics and transcriptomics to investigate the molecular features of selected cefiderocol-resistance of K. pneumoniae and found that the resistance of K. pneumoniae to cefiderocol was significantly related to the ability of biofilm formation. Downregulation of genes involved in biofilm formation including hdeB, stpA, yhjQ, fba, bcsZ, uvrY, bcsE, bcsC, and ibpB were the main factors that reduced the biofilm formation ability. In addition, downregulation of siderophore transporter proteins including the iron uptake system component efeO, the TonB-dependent receptor fecA, and ferric iron ABC transporter fbpA may be among the determining factors leading to cefiderocol resistance and promoting the reduction of biofilm formation ability of K. pneumoniae.

Figure 1 Proposed model based on the positive feedback effect between the reduction of biofilm formation ability and siderophore transporters proteins.

In this study, wild type (WT) strain K. pneumoniae NTUH-K2044 was cultured by using medium containing cefiderocol, and cefiderocol-resistant strains were isolated after 36 days. Through curve analysis, in vitro competition experiment, transmission electron microscopy analysis, biofilm formation ability test and carbon metabolism analysis, combined with the physical, chemical and biological properties of WT strain and cefiderocol-treated strain, and transcriptome and proteomic analysis, the adaptation mechanisms of K. pneumoniae to cefiderocol was found.

Figure 2 The cell wall thickness of cefiderocol-treated strain decreased significantly

Figure 3 The biofilm formation ability of cefiderocol-treated strain reduced significantly

Figure 4 Heatmap of the relative abundances of the DEGs shared by proteome and transcriptome

Figure 5 Interaction network of cefiderocol-treated strain’s proteins at protein level and transcription level

Professor Gu Bing and Professor Wang Chengbin are the co-corresponding authors of the paper. The research has been supported by the National Natural Science Foundation of China (81871734 and 81471994), the key R&D plan of Jiangsu Province (BE2020646), the medical talents fund of Jiangsu Province (ZDRCA2016053), the six categories of talents plan of Jiangsu Province (WSN-135), the senior health talents fund of the "Liuyi Project" of Jiangsu Province (LGY2016042), and the special fund for "Peak Climbing Plan" scientific researches (2021DFJH0008).

Team Introduction

Professor Gu Bing, imported talents of Guangdong Provincial People's Hospital in 2021, director of Clinical Laboratory Department, vice chairman of the Youth Committee of the Chinese Society of Laboratory Medicine of Chinese Medical Association, vice president of the Society of Laboratory Medicine of China Association of Medical Equipment, and the key medical talent of "strengthening health through science and education" project, "333 project", "six categories of talents plan" and "Liuyi Project" of Jiangsu Province. He has presided over 4 National Natural Science Foundation projects and 8 provincial and ministerial projects; participated in one key R&D plan supported by the Ministry of Science and Technology; and published more than 80 SCI papers as the first or communication author, with a cumulative impact factor of more than 260 points.

Professor Wang Chengbin, chief physician of the Chinese PLA General Hospital, chairman of the Chinese Society of Laboratory Medicine of Chinese Medical Association, member of the Standing Committee and former chairman of the Society of Laboratory Medicine of the CMA Beijing Branch, members of the board of the International Society for Laboratory Hematology (ISLH), and editorial board member of the National Medical Journal of China. He has undertaken researches supported by national key R&D special projects, national major instrument special projects, National Science and Technology Support Program, and National Natural Science Foundation, and published more than 300 academic papers in domestic and foreign journals, more than 100 of which are SCI papers. Prof. Wang has edited or translated 7 monographs.

Text: Zhao Yunhu, Photo: Hu Xuejiao