Vancomycin is a crucial last-resort antibiotic for tackling Gram-positive bacterial infections. However, its potency fails against the more difficult-to-treat Gram-negative bacteria (GNB). Vancomycin derivatives have shown promise as broad-spectrum antibacterials, but are still underexplored.
View Article and Find Full Text PDFThe rise in antimicrobial resistance, the increasing occurrence of bacterial, and fungal infections, and the challenges posed by polymicrobial biofilms necessitate the exploration of innovative therapeutic strategies. Silver-based antimicrobials have garnered attention for their broad-spectrum activity and multimodal mechanisms of action. However, their effectiveness against single-species or polymicrobial biofilms remains limited.
View Article and Find Full Text PDFBiofilm-mediated wound infections pose a significant challenge due to the limitations of conventional antibiotics, which often exhibit narrow-spectrum activity, fail to eliminate recurrent bacterial contamination, and are unable to penetrate the biofilm matrix. While the search for alternatives has explored the use of metal nanoparticles and synthetic biocides, these solutions often suffer from unintended toxicity to surrounding tissues and lack controlled administration and release. In this study, we engineered a pH-responsive release-active dressing film based on carboxymethyl cellulose, incorporating a synthetic antibacterial molecule (SAM-17).
View Article and Find Full Text PDFThe increasing prevalence of drug-resistant infections caused by Gram-positive bacteria poses a significant threat to public healthcare. These pathogens exhibit not only smart resistance mechanisms but also form impenetrable biofilms on various surfaces, rendering them resilient to conventional therapies. In this study, we present the potent antibacterial activity of a synthetic ion transporter T against multi-drug resistant (MDR) Gram-positive pathogens, with minimum inhibitory concentration (MIC) values ranging from 0.
View Article and Find Full Text PDFManagement of infections at ocular injury often requires prolonged and high dose of antibiotic, which is associated with challenges of antibiotic resistance and bacterial biofilm formation. Tissue glues are commonly used for repairing ocular tissue defects and tissue regeneration, but they are ineffective in curing infection. There is a critical need for antibacterial ocular bio-adhesives capable of both curing infection and aiding wound closure.
View Article and Find Full Text PDFCatheter-associated urinary tract infections (CAUTIs) pose a significant challenge in hospital settings. Current solutions available on the market involve incorporating antimicrobials and antiseptics into catheters. However, challenges such as uncontrolled release leading to undesirable toxicity, as well as the prevalence of antimicrobial resistance reduce the effectiveness of these solutions.
View Article and Find Full Text PDFThe rise of multidrug-resistant bacterial infections and the dwindling supply of newly approved antibiotics have emerged as a grave threat to public health. Toward the ever-growing necessity of the development of novel antimicrobial agents, herein, we synthesized a series of cationic amphiphilic biocides featuring two cationic headgroups separated by different hydrophobic spacers, accompanied by the inclusion of two lipophilic tails through cleavable ester functionality. The detailed aggregation properties offered by these biocides were investigated by small-angle neutron scattering (SANS) and conductivity.
View Article and Find Full Text PDFDespite advancements in preventive measures and hospital protocols, surgical site infections (SSIs) remain a significant concern following surgeries. Sutures, commonly used for wound closure, can serve as a platform for microbial adherence and contamination, leading to extensive debridement and recurrent antibiotic therapy. The emergence of drug resistance and the formation of biofilms on sutures have further complicated the management of SSIs.
View Article and Find Full Text PDFThe emergence of antimicrobial resistance (AMR) in pathogenic bacteria, expedited by the overuse and misuse of antibiotics, necessitates the development of a rapid and pan-territorially accessible diagnostic protocol for resistant bacterial infections, which would not only enable judicious prescription of drugs, leading to infection control but also augment AMR surveillance. In this study, we introduce for the first time a "" terbium (Tb) photoluminescence assay supported on a paper-based platform for rapid point-of-care (POC) detection of β-lactamase (BL)-producing bacteria. We strategically conjugated biphenyl-4-carboxylic acid (), a potent Tb sensitizer, with cephalosporin to engineer a BL substrate , where the energy transfer to terbium is arrested.
View Article and Find Full Text PDFGram-negative bacterial infections pose a significant challenge due to two major resistance elements, including the impermeability of the outer membrane and the overexpression of efflux pumps, which contribute to antibiotic resistance. Additionally, the coexistence of multispecies superbugs in mixed species biofilms further complicates treatment, as these infections are refractory to most antibiotics. To address this issue, combining obsolete antibiotics with non-antibiotic adjuvants that target bacterial membranes has shown promise in combating antibacterial resistance.
View Article and Find Full Text PDFACS Appl Bio Mater
November 2023
Wound dressings play a crucial role in facilitating optimal wound healing and protecting against microbial infections. However, existing commercial options often fall short in addressing chronic infections due to antibiotic resistance and the limited spectrum of activity against both Gram-positive and Gram-negative bacteria frequently encountered at wound sites. Additionally, complex fabrication processes and cumbersome administration strategies pose challenges for cost-effective wound dressing development.
View Article and Find Full Text PDFThe emergence of antimicrobial resistance, coupled with the occurrence of persistent systemic infections, has already complicated clinical therapy efforts. Moreover, infections are also accompanied by strong inflammatory responses, generated by the host's innate and adaptive immune systems. The closely intertwined relationship between bacterial infection and inflammation has multiple implications on the ability of antibacterial therapeutics to tackle infection and inflammation.
View Article and Find Full Text PDFGuest editors Jayanta Haldar, Sylvie Garneau-Tsodikova and Micha Fridman introduce the themed collection on 'Antibiotic microbial resistance'.
View Article and Find Full Text PDFMicrobial colonization on urinary and intravascular catheter surfaces results in steeply rising cases of catheter-associated infections as well as blood stream infections. Currently marketed efforts include impregnation and loading of antimicrobials and antiseptics that leach out into the local environment and inactivate microbes. However, they suffer from uncontrolled release, induction of resistance, and undesired toxicity.
View Article and Find Full Text PDFPeptidomimetic antimicrobials exhibit a selective interaction with bacterial cells over mammalian cells once they have achieved an optimum amphiphilic balance (hydrophobicity/hydrophilicity) in the molecular architecture. To date, hydrophobicity and cationic charge have been considered the crucial parameters to attain such amphiphilic balance. However, optimization of these properties is not enough to circumvent unwanted toxicity towards mammalian cells.
View Article and Find Full Text PDFThe problem of antibiotic resistance is on the rise, with multidrug-resistant strains emerging even to the last resort antibiotics. The drug discovery process is often stalled by stringent cut-offs required for effective drug design. In such a scenario, it is prudent to delve into the varying mechanisms of resistance to existing antibiotics and target them to improve antibiotic efficacy.
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