An Explorative Review on Advanced Approaches to Overcome Bacterial Resistance by Curbing Bacterial Biofilm Formation

Abstract

The continuous emergence of multidrug-resistant pathogens evoked the development of innovative approaches targeting virulence factors unique to their pathogenic cascade. These approaches aimed to explore anti-virulence or anti-infective therapies. There are evident concerns regarding the bacterial ability to create a superstructure, the biofilm. Biofilm formation is a crucial virulence factor causing difficult-to-treat, localized, and systemic infections. The microenvironments of bacterial biofilm reduce the efficacy of antibiotics and evade the host’s immunity. Producing a biofilm is not limited to a specific group of bacteria; however, Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus biofilms are exemplary models. This review discusses biofilm formation as a virulence factor and the link to antimicrobial resistance. In addition, it explores insights into innovative multi-targeted approaches and their physiological mechanisms to combat biofilms, including natural compounds, phages, antimicrobial photodynamic therapy (aPDT), CRISPR-Cas gene editing, and nano-mediated techniques.

Keywords:

• bacterial biofilms
• natural compounds
• phages
• aPDT
• CRISPR
• nanotechnology

Abbreviation

agr, accessory gene regulator genes; AHL, N-acyl homoserine lactones; AI, autoinducers; aPDT, antimicrobial photodynamic therapy; Cas, complex sensing systems; CRISPR, Clustered Regulatory Interspaced Short Palindromic Repeats; ECM, extracellular matrix; eDNA, extracellular DNA; EPS, extracellular polymeric substances; HAI, hospital-acquired infection; MBIC, minimum biofilm inhibitory concentration; MDR, multi-drug resistance; NP/NPs, nanoparticle; PS, photosensitizer; QQ systems, quorum quenching systems; QS systems, quorum sensing systems.

Acknowledgment

This work was supported by a grant from King Abdullah International Research Center, National Guard Health Affairs, Riyadh, Saudi Arabia (Grant No. RC20/109/R). The funding agency had no role in the decision to publish or prepare the manuscript. Figures were created with BioRender.com.

Disclosure

The authors report no conflicts of interest in this work.