Zinc oxide nanoparticles prevent multidrug resistant Staphylococcus-induced footpad dermatitis in broilers.

The current experiment was designed to evaluate the effects of dietary supplementations of zinc oxide nanoparticles (ZONPs) on some behavioural, performance, welfare and histopathological changes in broilers exposed to multidrug resistant Staphylococcus aureus (MRSA)-induced footpad dermatitis (FPD). Eighty-four male Indian River (IR) broilers were randomly allotted to six different dietary treatments as follows: C-ve, C+ve, 10, 20, 30 and 40 ppm ZONPs from 7 to 49d of age. At day 28, broilers (n = 70) were sub-cutaneously injected with 0.5 ml of saline containing 5.3 × 107 CFU/ml of S. aureus (MRSA) in each metatarsal foot pad. Control (non-infected) broilers were given 0.5 ml of saline (n = 14). Results clarified that non-infected birds and ZONPs-fed birds had significantly higher standing and feeding activities and lower resting activities in comparison with the infected group. Also, the S. aureus infected group had significantly lower body weight gain (BWG) and higher feed conversion ratio (FCR) than the non-infected group. In addition, the non-infected birds and ZONPs groups had significantly lower object crossing and tonic immobility times (TI) and gait scores (GS) in comparison with the S. aureus group. Only ZONPs 30, 40 ppm and non-infected groups had a significantly higher latency to lie time (LLT) and lower serum cortisol level in comparison with the S. aureus group. Moreover, there were significant changes in the gross lesion score and histopathological lesions between the different groups. In conclusion, the dietary supplementation of ZONPs can reduce S. aureus-induced negative effects of FPD in broilers.

Repurposing auranofin for the treatment of cutaneous staphylococcal infections.

The scourge of multidrug-resistant bacterial infections necessitates the urgent development of novel antimicrobials to address this public health challenge. Drug repurposing is a proven strategy to discover new antimicrobial agents; given that these agents have undergone extensive toxicological and pharmacological analysis, repurposing is an effective method to reduce the time, cost and risk associated with traditional antibiotic innovation. In this study, the in vitro and in vivo antibacterial activities of an antirheumatic drug, auranofin, was investigated against multidrug-resistant Staphylococcus aureus. The results indicated that auranofin possesses potent antibacterial activity against all tested strains of S. aureus, including meticillin-resistant S. aureus (MRSA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA), with minimum inhibitory concentrations (MICs) ranging from 0.0625µg/mL to 0.125µg/mL. In vivo, topical auranofin proved superior to conventional antimicrobials, including fusidic acid and mupirocin, in reducing the mean bacterial load in infected wounds in a murine model of MRSA skin infection. In addition to reducing the bacterial load, topical treatment of auranofin greatly reduced the production of inflammatory cytokines, including tumour necrosis factor-α (TNFα), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß) and monocyte chemoattractant protein-1 (MCP-1), in infected skin lesions. Moreover, auranofin significantly disrupted established in vitro biofilms of S. aureus and Staphylococcus epidermidis, more so than the traditional antimicrobials linezolid and vancomycin. Taken together, these results support that auranofin has potential to be repurposed as a topical antimicrobial agent for the treatment of staphylococcal skin and wound infections.

Impact of different cell penetrating peptides on the efficacy of antisense therapeutics for targeting intracellular pathogens.

There is a pressing need for novel and innovative therapeutic strategies to address infections caused by intracellular pathogens. Peptide nucleic acids (PNAs) present a novel method to target intracellular pathogens due to their unique mechanism of action and their ability to be conjugated to cell penetrating peptides (CPP) to overcome challenging delivery barriers. In this study, we targeted the RNA polymerase α subunit (rpoA) using a PNA that was covalently conjugated to five different CPPs. Changing the conjugated CPP resulted in a pronounced improvement in the antibacterial activity observed against Listeria monocytogenes in vitro, in cell culture, and in a Caenorhabditis elegans (C. elegans) infection model. Additionally, a time-kill assay revealed three conjugated CPPs rapidly kill Listeria within 20 minutes without disrupting the bacterial cell membrane. Moreover, rpoA gene silencing resulted in suppression of its message as well as reduced expression of other critical virulence genes (Listeriolysin O, and two phospholipases plcA and plcB) in a concentration-dependent manner. Furthermore, PNA-inhibition of bacterial protein synthesis was selective and did not adversely affect mitochondrial protein synthesis. This study provides a foundation for improving and developing PNAs conjugated to CPPs to better target intracellular pathogens.