Light Triggered Enhancement of Antibiotic Efficacy in Biofilm Elimination Mediated by Gold-Silver Alloy Nanoparticles

Abstract

Bacterial biofilm is a tri-dimensional complex community of cells at different metabolic stages involved in a matrix of self-produced extracellular polymeric substances. Biofilm formation is part of a defense mechanism that allows the bacteria to survive in hostile environments, such as increasing resistance or tolerance to antimicrobial agents, causing persistent infections hard to treat and impair disease eradication. One such example is bovine mastitis associated with Streptococcus dysgalactiae subsp. dysgalactiae (SDSD), whose worldwide health and economic impact is on the surge. As such, non-conventional nanobased approaches have been proposed as an alternative to tackle biofilm formation and to which pathogenic bacteria fail to adapt. Among these, metallic nanoparticles have gained significant attention, particularly gold and silver nanoparticles, due to their ease of synthesis and impact against microorganism growth. This study provides a proof-of-concept investigation into the use of gold-silver alloy nanoparticles (AuAgNPs) toward eradication of bacterial biofilms. Upon visible light irradiation of AuAgNPs there was considerable disturbance of the biofilms’ matrix. The hindering of structural integrity of the biofilm matrix resulted in an increased permeability for entry of antibiotics, which then cause the eradication of biofilm and inhibit subsequent biofilm formation. Additionally, our results that AuAgNPs inhibited the formation of SDSD biofilms via distinct stress pathways that lead to the downregulation of two genes critical for biofilm production, namely, brpA-like encoding biofilm regulatory protein and fbpA fibronectin-binding protein A. This study provides useful information to assist the development of nanoparticle-based strategies for the active treatment of biofilm-related infections triggered by photoirradiation in the visible.

Assessing in vivo and in vitro biofilm development by Streptococcus dysgalactiae subsp. dysgalactiae using a murine model of catheter-associated biofilm and human keratinocyte cell

“…In fact, in recent years, the association of SDSD with human infections such as cellulitis has been reported ( Chennapragada et al., 2018 ; Nathan et al., 2021 ), and one case of cellulitis rapidly progressed to septic shock ( Nathan et al., 2021 ). Indeed, we have recently reported for the first time the resistance to conventional antibiotics associated with biofilm formation by SDSD ( Alves-Barroco et al., 2022 ), which may complicate the treatment of some infections associated with this subspecies.…”

Recent advances in nanoantibiotics against multidrug-resistant bacteria

“…84 In the case of Pseudomonas aeruginosa and Pseudomonas baumannii , 34 many strains can acquire MDR genes through HGT, which can reduce the effectiveness of β-lactam 81 antibiotics. 85 Overuse and misuse of antibiotics have created a strong selective pressure on bacteria, at the same time, HGT provides a rapid pathway for bacteria to develop antibiotic resistance. 84 So, proper use of antibiotics and strict control of infectious diseases are essential in preventing the spread of antibiotic resistance in different pathogens.…”

“…Thus, HGT can help bacteria acquire new resistance genes and adapt to changing environments. 85 Pseudomonas aeruginosa (Gram-negative bacteria) formed biofilms in the lungs of cystic fibrosis and developed resistance to tobramycin, while Staphylococcus aureus (Gram-positive bacteria) formed biofilms on medical devices and developed resistance to β-lactam antibiotics. 87 NMs have been suggested as a potential solution to overcome biofilm resistance.…”