Growing antimicrobial resistance and the resilience of biofilm infections have led researchers to study the potential of antimicrobial combinations, including those incorporating enzymes with biofilm-disrupting abilities. This work aimed to evaluate the journey of antimicrobial-enzyme combination research and to gain insights into its current status and most promising leads. Expert curators annotated and analysed all published experimental data on enzyme-containing combinations for two major biofilm-forming pathogens, namely Pseudomonas aeruginosa and Staphylococcus aureus. This entailed the construction of the first publicly accessible online database on antimicrobial-enzyme combinations, the Antimicrobial Enzyme Combinations Database (https://www.ceb.uminho.pt/aecd). Gathered data were also reconstructed as knowledge networks to help analyse and visualise annotated entities (e.g. enzymes, methods, strains, combination outputs). The database currently holds 122 and 206 annotated combinations for P. aeruginosa and S. aureus, respectively, and their analysis allowed a systematic review of the available evidence on enzyme combinations, reliably illustrating the studies being performed. The most tested enzymes (e.g. lysozyme, DNase, lysostaphin) were scrutinised and the rationale behind each combination was explained. This research area is still growing although current research gaps/opportunities were identified, such as lack of biofilm testing and studies on polymicrobial scenarios. Hopefully, this work will shed light on the synergistic potential of enzyme combinations and alleviate some of the time- and resource-consuming tasks related to enzyme combination research by helping the selection and design of new enzyme-related therapeutic options for P. aeruginosa and S. aureus infections.
Keywords: Antimicrobial combinations; Database; Enzymes; Pseudomonas aeruginosa; Staphylococcus aureus.
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