Editorial: Novel Strategies to Target Biofilm Formation in ESKAPE Pathogens for Combating Antimicrobial Resistance

Vinothkannan Ravichandran^1*Aiying Li^2*Satish Kumar Rajasekharan^3*

• ¹Amity University, Mumbai, Mumbai, India
• ²Shandong University, Jinan, China
• ³SRM Institute of Science and Technology (Deemed to be University) Research Kattankulathur, Kattankulathur, India

that combining phytocompounds with antibiotics can improve antibiofilm and bactericidal effectiveness against S. aureus, underscoring their promise in combinatorial therapy.The interaction between Staphylococcus aureus and Pseudomonas aeruginosa is known to enhance virulence, increase antimicrobial resistance, and slow wound healing, particularly in foot ulcers. Hilliard et al. (2024) investigated the application of Manuka honey, a known antibacterial and wound healing agent, integrated into PCL-gelatin scaffolds. Although soluble manuka honey was effective in inhibiting both planktonic and biofilm growth in co-cultures, the scaffoldembedded version did not directly inhibit or kill bacteria; rather, it promoted agrA expression in S. aureus. This study provides a detailed view of how honey-based wound care methods might affect biofilm dynamics, potentially reducing microbial persistence and complications related to wounds in ESKAPE infections. 2024) discovered that gallium nitrate [Ga(NO3)3] can effectively disrupt bacterial iron metabolism by acting like a "Trojan horse." Because Ga3+ shares the same ionic radius as Fe3+, it is easily absorbed by bacterial iron-acquisition systems but cannot be biochemically reduced, thus hindering crucial iron-dependent functions such as DNA synthesis and electron transport. This study highlights the importance of the environmental pH in determining the effectiveness of this transition metal. Acidic conditions greatly enhanced the vulnerability of P. aeruginosa to [Ga(NO3)3]. By identifying pH as a key factor in Ga bioavailability, they introduced a costeffective and scalable pharmacological approach that supports our aim of developing unconventional treatments to tackle antimicrobial-resistant pathogens.The widespread occurrence of dental caries continues to be a significant chronic health issue worldwide, impacting billions of people and becoming more complex due to the rise of methicillin- 2025) introduced a groundbreaking approach using the novel lytic phage vB_EfaS-1017, which is the first demonstration of the dose-independent eradication of VRE biofilms. When combined with levofloxacin, this offers an enhanced therapeutic strategy.Analysis of the phage genome confirmed the absence of virulence or resistance genes, thereby ensuring its safety for clinical use. In vitro studies showed that vB_EfaS-1017 eliminated 95% of cells within an hour. Importantly, in mouse bacteremia models, phage therapy alone saved 60% of the mice, levofloxacin alone saved 40%, and the combination therapy saved 80%, while reducing phage resistance to 30%, bacterial load, and inflammation. This treatment uniquely restores beneficial gut microbiota, such as Lactobacillus and Alloprevotella, and provides prophylactic treatment windows, establishing phage-antibiotic synergy as the new gold standard for treating multidrug-resistant enterococcal infections.Klebsiella pneumoniae, a carbapenem-resistant "superbug" and part of the ESKAPE group of pathogens, is responsible for severe hospital-acquired infections in patients with weakened immune systems owing to its biofilm-driven multidrug resistance.