Bacteria‐Responsive Multidrug Delivery Nanosystem for Combating Long‐Term Biofilm‐Associated Infections

Abstract

Microbial biofilm formation on implantable devices causes chronic infections that cannot be treated with existing antimicrobials. Quorum sensing inhibitors (QSIs) have recently emerged as novel antimicrobials for the prevention of biofilm formation. But blocking QS alone is insufficient to inhibit biofilmassociated chronic infections. Herein, chitosan hollow nanospheres are capped by bacteria-responsive β-casein to form a synergistic antifouling nanosystem consisting of a QSI and bactericide. β-casein is degraded by protease in a bacteria-colonized microenvironment in situ thus, QSI and bactericide are released sequentially. The release of QSI sensitises bacteria effectively through reduction of surface hydrophobicity, eDNA content, and lipopolysaccharide production in biofilms, amplifying the chemotherapeutic action of the bactericide. Compared to the uncoated surface, the coated surface inhibits biofilm formation and removes preformed biofilms of Pseudomonas aeruginosa PAO1 and methicillin-resistant Staphylococcus aureus by 1.8 logs and 1.9 logs of biomass inhibition, respectively. The coated catheters are found to stay clean for 30 days under artificial urine flow, while the uncoated catheters are clogged by bacterial biofilms within 5 days. Finally, the long term antifouling activity in vivo is confirmed. Overall, the nanosystem is devoted to making urinary catheters resistant to bacterial biofilm formation for the long term.

Roles of transcriptional factor PsrA in the regulation of quorum sensing in Pseudomonas aeruginosa PAO1

“…Another example of a natural quorum-sensing inhibitor is curcumin. When coupled with or coated onto different nanoparticles, these inhibitors exhibit a synergistic antifouling effect, eradicating biofilm formation from P. aeruginosa on urinary catheter surfaces ( Prateeksha et al, 2019 , 2021 , 2023 ; Kumar et al, 2022 ). These promising approaches represent potential alternatives for the development of new antimicrobial strategies.…”

Multifunctional Casein-Based Wound Dressing Capable of Monitoring and Moderating the Proteolytic Activity of Chronic Wounds

“…27 Zhu and colleagues developed a photocurable casein-based hydrogel with the perspective application in emergency wounds. 28 The susceptibility of casein to proteolysis has been exploited in protease assays 29 and for developing systems that respond to bacterial proteases 30 or the proteolytic milieu of tumor tissues. 31 The present research aimed to develop a casein-based substrate that responds to a variety of proteases offers insight into the overall proteolytic activity rather than just the activity of one or two specific proteases, and does this without depending on a special instrument, kit, or even skill.…”

“… 27 Zhu and colleagues developed a photocurable casein-based hydrogel with the perspective application in emergency wounds. 28 The susceptibility of casein to proteolysis has been exploited in protease assays 29 and for developing systems that respond to bacterial proteases 30 or the proteolytic milieu of tumor tissues. 31 …”

Table_2.DOCX

“…Another example of a natural quorum-sensing inhibitor is curcumin. When coupled with or coated onto different nanoparticles, these inhibitors exhibit a synergistic antifouling effect, eradicating biofilm formation from P. aeruginosa on urinary catheter surfaces (Prateeksha al., 2019(Prateeksha al., , 2021(Prateeksha al., , 2023Kumar et al, 2022). These promising approaches represent potential alternatives for the development of new antimicrobial strategies.…”