Molecular Mechanisms Knowledge and Phenotypic Screening Should be Complementary Approaches for Effective Not Risky Antibiofilm Research

Biofilms (BFs) bacteria are dramatically intensifying tolerance to conventional antibiotics, no longer effective. Therefore, the research for new antibiofilm (ABF) compounds are noticeably in-creasing the studies proliferation rate. In this regard, intriguing questions raise to be debated and here the tension “between efficacy and understanding” has been afforded. Questions could include: i) are BF mechanistic studies indispensable and strictly required, especially at Academic levels, where economic support is scarce? ii) When may a purely phenotypic approach still hold interest for relevant journals requirements? iii) Could be empirical efficacy alone, sufficient for the relevance of the study in effective ABF research? iv) Do high costs, long times mechanistic insights, also associated with environmental issues, represent the necessary key to defeating BFs and the benchmark that determines the scientific appreciation and impact of a study? To capture also attention of readers not so expert in the field, the state of the art of global challenge against BF, responsible for difficult-to-treat and even lethal chronic infection, has been provided. The available armamentarium of functioning antibiotics/combinations against BF has been discussed, modern ABF compounds classification has been reported, while the relevant investigations to be performed to indagate ABF mechanisms has been clarified. 126 studies on the ABF activity were considered and distributed in Tables and discussed. Unexpectedly, experimentally validated causal molecular mechanisms have been found in only 34 ones. 92 out of 126 papers, stopped research at phenotypic screenings or descriptive clues and are in the literature. Such approach represents the main trend of most recent literature, as a mirror of limited resources of most part of Academic laboratories and progressive publication growth over time. Anyway, despite mere phenotypic studies are the most abundant in literature, mechanistic insights should be comple-mentary for an efficacious ABF research and to avoid risks including poor rational lead optimization, risk of false positive phenotypic results, limited inter study reproducibility and major translational barriers.