Due to the increasing bacterial resistance to antibiotics, phage therapy represents a promising alternative for the treatment of chronic bacterial infections, among which infections caused by bacteria of the genus Staphylococcus are common. Bacteria in natural and clinical environments differ significantly in their metabolic state from those typically studied under laboratory conditions, where growth conditions are generally optimal and do not reflect the real environments. Therefore, to reliably predict the effectiveness of phage therapy, it is essential to study the action of bacteriophages in bacteria found in nutrient-limited environments. In this study, we investigated the influence of the physiological state of Staphylococcus capitis bacteria on phage infection and the replication of the lytic bacteriophage K. The bacterium was cultivated in a chemostat at different dilution rates (D), which allowed precise control of its specific growth rate (µ) and thus its metabolic state. Phage infection efficiency was evaluated by determining phage growth parameters that describe the progression of the lytic cycle and the success of phage multiplication. Phage parameter values obtained for bacteria with reduced metabolic activity were compared with those measured in exponentially growing bacteria. We found that in metabolically weakened bacterial cells, the latent period (LP) was longer, while the burst size (BS) decreased linearly with decreasing bacterial growth rate. The adsorption constant (ka) reached its highest values in extremely slow-growing bacteria, which we attribute to a weakened cell wall structure. At the same time, the adsorption constant was also high in exponentially growing bacteria. Based on the phage parameters, we calculated phage fitness (FF) as an overall indicator of phage infection efficiency. Phage therapy was most effective in exponentially growing bacteria, where active host metabolism supports rapid phage replication and efficient lysis. In contrast, phage fitness markedly decreased at low bacterial growth rates. Although phage therapy is limited in slowly growing bacteria, it is not completely ineffective, as phage fitness remains positive despite reduced host metabolic activity. Phage production and lysis still occur, but with reduced efficiency. The dependence of phage parameters and phage fitness on the host’s physiological state was described using mathematical models.
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