Inosine and D-Mannose Secreted by Drug-Resistant Klebsiella pneumoniae Affect Viability of Lung Epithelial Cells

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 9; p. 2994
• Main Authors: Zhang, Yuhan, Zhou, Ziwei, Xiao, Wenxuan, Tang, Yuting, Guan, Wei, Wang, Jiang, Shu, Farui, Shen, Jiaqi, Gu, Shaoyan, Zhang, Lu, Wang, Qingzhong, Xie, Lixin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.05.2022; MDPI
• Subjects: A549; Actin; Adenosine; Antibiotic resistance; Antibiotics; Antimicrobial agents; Bacteria; Biofilms; Biomarkers; Capsular polysaccharides; Cholecystokinin; Cytoskeleton; Cytotoxicity; D-mannose; Discriminant analysis; Drug resistance; Epithelial cells; Epithelium; Genotype & phenotype; Immunofluorescence; Infections; inosine; Klebsiella; Klebsiella pneumoniae; Mannose; Metabolism; Metabolites; metabolomics; Morphology; Pathogenicity; Pathogens; Pneumonia; Polysaccharides; Proteins; Scanning electron microscopy; Tight junctions; Viability; inosine; drug resistance; D-mannose; metabolomics; Klebsiella pneumoniae; A549
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27092994

The antibiotic resistance rates of have been steadily increasing in recent years. Nevertheless, the metabolic features of the drug-resistant and its associated benefits for bacterial pathogenicity are far from expounded. This study aims to unravel the unique physiological and metabolic properties specific to drug-resistant . Using scanning electron microscopy (SEM), we observed a thicker extracellular mucus layer around a drug-resistant strain (Kp-R) than a drug-sensitive strain (Kp-S). Kp-R also produced more capsular polysaccharide (CPS) and biofilm, and appeared to have a significant competitive advantage when co-cultured with Kp-S. Moreover, Kp-R was easier to adhere to and invade A549 epithelial cells than Kp-S but caused less cell-viability damage according to cell counting kit-8 (CCK-8) tests. Immunofluorescence revealed that both Kp-R and Kp-S infection destroyed the tight junctions and F-actin of epithelial cells, while the damage caused by Kp-S was more severe than Kp-R. We detected the extracellular metabolites secreted by the two strains with UHPLC-Q-TOF MS to explore the critical secretion products. We identified 16 predominant compounds that were differentially expressed. Among them, inosine increased the viability of epithelial cells in a dose-dependent manner, and an A R antagonist can abolish such enhancement. D-mannose, which was secreted less in Kp-R, inhibited the viability of A549 cells in the range of low doses. These findings provide potential targets and research strategies for preventing and treating drug-resistant infections.