**7. Conclusion**

Outer membrane targeting is a revolutionary strategy for antibiotic discovery. Gram-negative pathogens will become sensitive to the range of clinically approved Gram-positive active antibiotics when their OM is perturbed. In this way, chemical space compatible with novel antimicrobial peptides would be expanded. However, there are many obstacles before performing this approach in the clinic successfully. The success or failure of this approach depends on the correct selection or development of the outer membrane perturbant and antibiotic adjutant combination. In comparison to monotherapy approaches as other combination therapies, dosage optimizing for adequate overlap in bioavailability approves difficulty and needs

more complicated clinical trials [77]. Spontaneous resistance development, horizontally acquired resistance genes, and biofilm formations are all significant barriers to successful antibiotic treatment. The capacity for OM disruption to overcome many of these challenges, uniquely positioning this approach among discovery efforts in the Gram-negative resistance crisis [19].
