Exogenous amino acids and saccharides mediate the sensitivity of Klebsiella pneumoniae phage.

UNLABELLED: Klebsiella pneumoniae is a major opportunistic pathogen responsible for severe infections, particularly in nosocomial settings. The increasing prevalence of multidrug-resistant strains has greatly limited the effectiveness of conventional antibiotics, highlighting the urgent need for alternative therapeutic strategies. Phage therapy has emerged as a promising approach; however, its efficacy is often influenced by bacterial physiological states, leading to variability in phage susceptibility. Amino acids and saccharides, as essential nutritional components, play important roles in bacterial growth and metabolism. Nevertheless, the mechanisms by which these nutrients affect bacterial physiological states and subsequently modulate susceptibility to phage infection remain poorly understood. In this study, the effects of 18 exogenous amino acids and eight saccharides on the growth of K. pneumoniae were assessed, and the variations in phage adsorption sensitivity of the treated bacteria were analyzed. Additionally, the impact of exogenous carbon sources on bacterial characteristics was further investigated through minimum inhibitory concentration (MIC) and biofilm formation assays. Compared with the control group, phage adsorption efficiency was significantly reduced after carbon source treatment. Furthermore, MIC values and biofilm formation capacity were altered to varying degrees, indicating that environmental nutrient conditions may influence the efficacy of phage therapy against drug-resistant K. pneumoniae infection. IMPORTANCE: The success of phage therapy depends not only on phage properties but also on the physiological state of the bacterial host. Although nutrients are fundamental determinants of bacterial metabolism and growth, their effects on phage susceptibility remain poorly characterized. Here, we systematically evaluated the influence of multiple amino acids and saccharides on K. pneumoniae and demonstrated that nutrient availability can markedly alter bacterial susceptibility to phage adsorption. In addition, nutrient-induced changes were associated with variations in antimicrobial susceptibility and biofilm formation. These findings highlight the importance of environmental nutritional conditions in shaping phage-host interactions and suggest that nutrient availability should be considered when optimizing phage-based strategies against multidrug-resistant bacterial infections.