Site-level cutaneous phenotyping framework for anti-MDA5-positive dermatomyositis: exploratory associations with systemic immune reference markers.

subsp. serovar Pullorum ( Pullorum) is a pathogen that exclusively infects poultry, causing acute septicemia in chicks and chronic asymptomatic infections in adult birds, along with impairment of the reproductive system [–]. It can induce extremely high mortality, potentially close to 100%, in young chickens and turkeys during the first 2–3 weeks post-hatch [], and the disease is particularly prevalent in Asia, where it causes substantial economic losses []. Nowadays, the rise of antimicrobial resistance (AMR) has been recognized as an emerging threat to public health [], and phages are considered an effective weapon against these drug-resistant strains [], including . Pullorum []. However, the rapid development of phage resistance still limits their therapeutic efficacy []. Although the emergence of phage-resistant bacteria is inevitable, there is growing evidence showing that phage-imposed selection drives mutations, enabling bacteria to evade infection but with a fitness cost []. There is a growing body of literature showing that the fitness trade-off in phage-resistant bacteria includes growth defects [], inability to form biofilm [, ], attenuated virulence [–], enhanced clearance by immune cells [], host colonization defects [], and increased sensitivity to antibiotics [, -]. Therefore, strategically exploiting the fitness costs inherent to phage resistance represents a promising approach for improving the clinical therapeutic success of phage therapy. Typically, for successful phage therapy, the phage must complete its entire lytic cycle of receptor adsorption, genome injection, virion assembly, and release []. In many instances, lytic phages must first recognize and adsorb to receptors on the bacterial surface []. Given that evolved phage resistance often involves mutations in bacterial cell surface receptors that are important for cellular stability and function [], and '“steering” survivors towards deleterious surface mutations can potentially improve treatment outcomes [], it is clear that taking advantage of these receptor changes to create a combinatorial phage cocktail will be the first important step in enhancing the cocktail’s efficacy.