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Abstract Antimicrobial resistance (AMR) leads to a decrease in the adequacy of antimicrobial agents and an increase in the rate of adverse effects and mortality. The main objective of this project is to investigate the synergistic effect of BiAu@NCLin-T1 and its substructures as an antimicrobial photodynamic therapy (aPDT) agent to combat microbial resistance. In addition, the effect of photothermal therapy (PTT) on some of the designed nanostructures at a temperature of 40 °C was also tested. The antimicrobial test was carried out using the growth curve method against Escherichia coli and Staphylococcus aureus. Computational methods were used to investigate the stability and entropy of oligonucleotide sequence structures. Various analyses were performed to identify the nanostructures, including Ultraviolet–visible (UV–vis) spectroscopy, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDS) and fluorescence analysis. The BiAu@NCLin-T1 appeared the significant aPDT impact against the gram-negative E.coli strain at two distinctive oligonucleotide concentrations (1, and 1.5 micromolar (µM)). Based on the results, the outlined nanostructures can act as a photosensitizer (PS), a photothermal treatment (PTT) agent, and an antimicrobial agent to combat resistant bacteria.

Abstract The use of antimicrobial drugs in food-producing animals contributes to the selection pressure on pathogenic and commensal bacteria to become resistant. This study aims to evaluate the existence of trade-offs between treatment effectiveness, cost, and the dynamics of resistance in gut commensal bacteria. We developed a within-host ordinary differential equation model to track the dynamics of antimicrobial drug concentrations and bacterial populations in the site of infection (lung) and the gut. The model was parameterized to represent enrofloxacin treatment for bovine respiratory disease (BRD) caused by Pastereulla multocida in cattle. Three approved enrofloxacin dosing regimens were compared for their effects on resistance on P. multocida and commensal E. coli: 12.5 mg/kg and 7.5 mg/kg as a single dose, and 5 mg/kg as three doses. Additionally, we explored non-FDA-approved regimes. Our results indicated that both 12.5 mg/kg and 7.5 mg/kg as a single dose scenario increased the most the treatment costs and prevalence of P. multocida resistance in the lungs, while 5 mg/kg as three doses increased resistance in commensal E. coli bacteria in the gut the most out of the approved scenarios. A proposed non-FDA-approved scenario (7.5 mg/kg, two doses 24 h apart) showed low economic costs, minimal P. multocida, and moderate effects on resistant E. coli. Overall, the scenarios that decrease P. multocida, including resistant P. multocida did not coincide with those that decrease resistant E. coli the most, suggesting a trade-off between both outcomes. The sensitivity analysis suggests that bacterial populations were the most sensitive to drug conversion factors into plasma ( $${\beta}$$ β ), elimination of the drug from the colon ( $$\vartheta$$ ϑ ), fifty percent sensitive bacteria (P. multocida) killing effect ( $${\text{L}}_{\text{s50}}$$ L s50 ), fifty percent of bacteria (E. coli) above ECOFF killing effect ( $${\text{C}}_{\text{r50}}$$ C r50 ), and net drug transfer rate in the lung ( $$\gamma$$ γ ) parameters.

Antimicrobial resistance (AMR) leads to a decrease in the adequacy of antimicrobial agents and an increase in the rate of adverse effects and mortality. The main objective of this project is to investigate the synergistic effect of BiAu@NCLin-T1 and its substructures as an antimicrobial photodynamic therapy (aPDT) agent to combat microbial resistance. In addition, the effect of photothermal therapy (PTT) on some of the designed nanostructures at a temperature of 40 °C was also tested. The antimicrobial test was carried out using the growth curve method against Escherichia coli and Staphylococcus aureus. Computational methods were used to investigate the stability and entropy of oligonucleotide sequence structures. Various analyses were performed to identify the nanostructures, including Ultraviolet–visible (UV–vis) spectroscopy, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDS) and fluorescence analysis. The BiAu@NCLin-T1 appeared the significant aPDT impact against the gram-negative E.coli strain at two distinctive oligonucleotide concentrations (1, and 1.5 micromolar (µM)). Based on the results, the outlined nanostructures can act as a photosensitizer (PS), a photothermal treatment (PTT) agent, and an antimicrobial agent to combat resistant bacteria. [ABSTRACT FROM AUTHOR]

The use of antimicrobial drugs in food-producing animals contributes to the selection pressure on pathogenic and commensal bacteria to become resistant. This study aims to evaluate the existence of trade-offs between treatment effectiveness, cost, and the dynamics of resistance in gut commensal bacteria. We developed a within-host ordinary differential equation model to track the dynamics of antimicrobial drug concentrations and bacterial populations in the site of infection (lung) and the gut. The model was parameterized to represent enrofloxacin treatment for bovine respiratory disease (BRD) caused by Pastereulla multocida in cattle. Three approved enrofloxacin dosing regimens were compared for their effects on resistance on P. multocida and commensal E. coli: 12.5 mg/kg and 7.5 mg/kg as a single dose, and 5 mg/kg as three doses. Additionally, we explored non-FDA-approved regimes. Our results indicated that both 12.5 mg/kg and 7.5 mg/kg as a single dose scenario increased the most the treatment costs and prevalence of P. multocida resistance in the lungs, while 5 mg/kg as three doses increased resistance in commensal E. coli bacteria in the gut the most out of the approved scenarios. A proposed non-FDA-approved scenario (7.5 mg/kg, two doses 24 h apart) showed low economic costs, minimal P. multocida, and moderate effects on resistant E. coli. Overall, the scenarios that decrease P. multocida, including resistant P. multocida did not coincide with those that decrease resistant E. coli the most, suggesting a trade-off between both outcomes. The sensitivity analysis suggests that bacterial populations were the most sensitive to drug conversion factors into plasma (β ), elimination of the drug from the colon (ϑ ), fifty percent sensitive bacteria (P. multocida) killing effect ( L s50 ), fifty percent of bacteria (E. coli) above ECOFF killing effect ( C r50 ), and net drug transfer rate in the lung (γ ) parameters. [ABSTRACT FROM AUTHOR]

Abstract The emergence of drug-resistant Mycobacterium tuberculosis strains is a threat to global health necessitating the discovery of novel chemotherapeutic agents. Natural products drug discovery, which previously led to the discovery of rifamycins, is a valuable approach in this endeavor. Against this backdrop, we set out to investigate the in vitro antimycobacterial properties of medicinal plants from Ghana and South Africa, evaluating 36 extracts and their 252 corresponding solid phase extraction (SPE) generated fractions primarily against the non-pathogenic Mycobacterium smegmatis and Mycobacterium aurum species. The most potent fraction was further evaluated in vitro against infectious M. tuberculosis strain. Crinum asiaticum (bulb) (Amaryllidaceae) emerged as the most potent plant species with specific fractions showing exceptional, near equipotent activity against the non-pathogenic Mycobacterium species (0.39 µg/ml ≤ MIC ≤ 25 µg/ml) with one fraction being moderately active (MIC = 32.6 µg/ml) against M. tuberculosis. Metabolomic analysis led to the identification of eight compounds predicted to be active against M. smegmatis and M. aurum. In conclusion, from our comprehensive study, we generated data which provided an insight into the antimycobacterial properties of Ghanaian and South African plants. Future work will be focused on the isolation and evaluation of the compounds predicted to be active.