The global challenge of antibiotic resistance has intensified the need for innovative approaches to combat infectious diseases, especially those caused by multi-drug resistant (MDR) bacteria. Additionally, pathogens such as Group A and B Streptococci, Clostridioides difficile, and a broad range of Gram-negative bacteria continue to present significant threats to public health, fueling outbreaks and complicating clinical management regardless of their antibiotic resistance profile. Recent advances have opened new avenues for targeted intervention through biologics—including vaccines, bacteriophages, lysins, monoclonal antibodies and in vivo expressed biologics —with the potential to disrupt bacterial pathogenesis more precisely and sustainably than traditional antibiotics.

This article collection focuses on combatting serious bacterial infections through the development of next-generation biologics targeting MDR bacteria and other clinically significant pathogens. We aim to highlight innovative research that explores novel bacterial elements as preventive or therapeutic targets, and evaluates the efficacy and underlying mechanisms of biologics in disrupting key processes essential for bacterial survival and pathogenicity. Special emphasis is placed on the interaction between these modern biologics and targeted pathogens, underscoring the translational potential of these interventions to prevent and control bacterial diseases.

The collection welcomes articles related but not limited to the following areas.

• Mechanisms of action for vaccines, phages, lysins, and antibodies against bacteria

• Studies identifying bacterial elements that serve as promising targets for biologic therapies

• Preclinical and clinical evaluation of monoclonal antibodies for inhibition of bacterial infections

• Novel vaccine designs targeting bacterial antigens

• The role of bacteriophages and phage-derived enzymes in overcoming antibiotic resistance

• Efficacy of in vivo expressed antibodies in the prevention and treatment of bacterial infections

• Combination therapy studies using biologics alongside traditional antimicrobials

• Insights into bacterial resistance mechanisms against biologics and strategies to mitigate them

• Advances in delivery systems to enhance the stability and bioavailability of lysins and antibodies in vivo

Topic editors Valeria Szijarto and Christine Tkaczyk are employed by AstraZeneca, Adriana Badarau is employed by BioNTech, and Gabor Nagy is employed by Cebina GMBH. All Topic Editors declare no competing interests with regards to the Research Topic subject.

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Innovative Biologics in the Battle Against Bacterial Pathogens: Disrupting Pathogenesis with Precision