Articles

Synergistic Antimicrobial Mechanisms of Antimicrobial Peptide-Coated Silver Nanoparticles for the Targeted Treatment of Multidrug-Resistant (MDR) Infections

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The emergence of multidrug-resistant (MDR) pathogens poses a critical challenge to global health, necessitating innovative antimicrobial solutions. This study focuses on the synthesis, characterization, and evaluation of antimicrobial peptides (AMP)-coated silver nanoparticles (AgNPs) as a novel approach to combating MDR infections. AMPs, known for their broad-spectrum activity and unique mechanisms, were isolated from Lacticaseibacillus casei and successfully precipitated using ammonium sulfate precipitation. The AMPs were conjugated with AgNPs to improve their stability, bioavailability, and antimicrobial efficacy.

AMP-coated AgNPs were synthesized and characterized using UV‒visible spectrophotometry, confirming the successful formation of nanoparticles. Antimicrobial and antifungal activities were assessed against a broad range of pathogens using the agar well diffusion method. The AMP-coated AgNPs exhibited enhanced activity compared to AMP alone, with significant inhibition zones observed for both bacterial and fungal strains. Synergy studies revealed that the combination of AMP-coated AgNPs with conventional antibiotics improved therapeutic efficacy, even at reduced dosages. Hemolysis assay evaluated the biocompatibility of the nanoparticles, indicating potential cytotoxicity of the silver nanoparticles at higher concentrations.

These findings underscore the promise of AMP-coated AgNPs as potent, broad-spectrum antimicrobial agents. However, the cytotoxic effects highlight the need for further research into optimizing biocompatibility. This study paves the way for developing advanced therapeutic strategies targeting MDR pathogens, offering an effective alternative to conventional antibiotics in critical healthcare applications.

Extended Spectrum β-Lactamase: Tackling Antibiotic Resistance and Overcoming Treatment Challenges

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Antibiotics, also known as antibacterials, kill or inhibit bacterial growth but are ineffective against viruses, fungi, or parasites, often leading to misuse. They are categorized by molecular structure, mode of action, and spectrum of activity. Antimicrobial Resistance (AMR) occurs when pathogens no longer respond to antimicrobial drugs, arising naturally or through acquisition. Resistance mechanisms include enzymatic (most common), genetic and physical. Bacteria produce various β-lactamases, such as Extended Spectrum β-lactamases (ESBLs), AmpC enzymes, and carbapenemase to exert resistance to Beta-Lactam (βL) class of antibiotics. ESBL families include TEM, SHV, and CTX-M, with E. coli being the most prevalent host. Any Gram-Negative Bacteria (GNB) can be an ESBL producer, but most common ones are the Enterobacteriaceae including Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca and Proteus mirabilis. ESBL-producing Enterobacteriaceae (ESBL-E) resist penicillin, aztreonam, and cephalosporins except cephamycins and carbapenems, posing a significant public health risk. Genetic resistance mechanisms involve random mutations and horizontal gene transfer through either of the following processes namely conjugation, transformation, transduction. Physical mechanisms include efflux pump production and decreased porin channels. In some microbiological laboratories, ESBL production are often not determined, rather resistance based on MIC values to third generation Cephalosporins are considered as resistance due to ESBL production. Antibiotic use in agriculture and medicine has increased Multi-drug resistant (MDR) ESBL-producing E. coli and evidenced in retail meat and among meat shop employees. Community-acquired ESBL-E infections are a growing concern, with hospital transmission primarily occurring among patients sharing rooms with ESBL carriers. Empirical and definitive therapies for ESBL-E infections must be adjusted based on Antibiotic Susceptibility Testing (AST). The MERINO trial identified urinary tract infections as the most common source of ESBL-E bacteremia, with E. coli being predominant. For critically ill patients with non-urinary tract infections, Meropenem or Imipenem-cilastatin are recommended. For uncomplicated UTIs, Nitrofurantoin, Cotrimoxazole, and Piperacillin-Tazobactam (Pip-Taz) are effective, while Cotrimoxazole, Fluoroquinolones, and Ceftolozane-tazobactam are suitable for complicated UTIs. New β-lactamase inhibitors like avibactam, vaborbactam, and relebactam are promising for treatment. Misuse of antibiotics, such as inappropriate dosing and duration, contributes to AMR, a growing global challenge. Deaths from AMR, estimated at 1.27 million in 2019, could reach 10 million by 2050. ESBLs drive the use of broad-spectrum antibiotics, accelerating resistance development. Inadequate therapy exacerbates infections, leading to prolonged hospital stays, complications, and increased mortality. Balancing new drug development with resistance emergence is crucial to combat AMR.