Antimicrobial resistance represents a public health problem with a major negative impact on health and socioeconomic development, and is one of the biggest threats in the modern era. This requires the discovery of new approaches to control microbial infections. Nanomedicine could be one of the promising strategies to improve the treatment of microbial infections. Polymer nanoparticles (PNPs) were reported to overcome the efflux-resistant mechanism toward chemotherapeutic agents. However, to the best of our knowledge, no studies were performed to explore their ability to overcome the efflux-resistant mechanism in bacteria. In the current study, azithromycin (AZI), a macrolide antibiotic, was encapsulated into a biocompatible polymer, poly (lactic-co-glycolic acid) (PLGA) using the nano-precipitation method. The effect of the drug to polymer ratio, surfactant, and pH of the aqueous medium on particle size and drug loading percentage (DL%) were investigated in order to maximize the DL% and control the size of NPs to be around 100 nm. The antibacterial activity of AZI-PLGA NPs was investigated against AZI-resistant bacteria; Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis (E. faecalis), where the efflux mechanism was demonstrated to be one of the resistant mechanisms. AZI-PLGA NPs were safer than free AZI, as revealed from the cytotoxicity test, and were able to overcome the efflux-resistant mechanism, as revealed by decreasing the MIC of AZI-PLGA NPs by four times than free AZI. The MIC value reduced from 256 to 64 µg/mL and from >1000 to 256 µg/mL for MRSA and E. faecalis, respectively. Therefore, encapsulation of AZI into PNPs was shown to be a promising strategy to overcome the efflux-resistant mechanism towards AZI and improve its antibacterial effect. However, future investigations are necessary to explore the effect (if any) of particle size, surface charge, and material composition of PNPs on antibacterial activity. Moreover, it is essential to ascertain the safety profiles of these PNPs, the possibility of their large-scale manufacture, and if this concept could be extended to other antibiotics.

COVID-19 is a pandemic disease caused by the SARS-CoV-2, which continues to cause global health and economic problems since emerging in China in late 2019. Until now, there are no standard antiviral treatments. Thus, several strategies were adopted to minimize virus transmission, such as social distancing, face covering protection and hand hygiene. Rhamnolipids are glycolipids produced formally by Pseudomonas aeruginosa and as biosurfactants, they were shown to have broad antimicrobial activity. In this study, we investigated the antimicrobial activity of rhamnolipids against selected multidrug resistant bacteria and SARS-CoV-2. Rhamnolipids were produced by growing Pseudomonas aeruginosa strain LeS3 in a new medium formulated from chicken carcass soup. The isolated rhamnolipids were characterized for their molecular composition, formulated into nano-micelles, and the antibacterial activity of the nano-micelles was demonstrated in vitro against both Gram-negative and Gram-positive drug resistant bacteria. In silico studies docking rhamnolipids to structural and non-structural proteins of SARS-CoV-2 was also performed. We demonstrated the efficient and specific interaction of rhamnolipids with the active sites of these proteins. Additionally, the computational studies suggested that rhamnolipids have membrane permeability activity. Thus, the obtained results indicate that SARS-CoV-2 could be another target of rhamnolipids and could find utility in the fight against COVID-19, a future perspective to be considered.

Hospital-acquired infections (HAIs) are considered to be a major global healthcare challenge, in large part because of the development of microbial resistance to currently approved antimicrobial drugs. HAIs are frequently preventable through infection prevention and control measures, with hand hygiene as a key activity. Improving hand hygiene was reported to reduce the transmission of healthcare-associated pathogens and HAIs. Alcohol-based hand sanitizers are commonly used due to their rapid action and broad spectrum of microbicidal activity, offering protection against bacteria and viruses. However, their frequent administration has been reported to be associated with many side effects, such as skin sensitivity, skin drying, and cracks, which promote further skin infections. Thus, there is an essential need to find alternative approaches to hand sanitation. Rhamnolipids are glycolipids produced by Pseudomonas aeruginosa, and were shown to have broad antimicrobial activity as biosurfactants. We have previously demonstrated the antimicrobial activity of rhamnolipid nano-micelles against selected drug-resistant Gram-negative (Salmonella Montevideo and Salmonella Typhimurium) and Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae). To the best of our knowledge, the antimicrobial activity of rhamnolipid nano-micelles in comparison to alcohol-based hand sanitizers against microorganisms commonly causing HAIs in Egypt—such as Acinetobacter baumannii and Staphylococcus aureus—has not yet been studied. In the present work, a comparative study of the antibacterial activity of rhamnolipid nano-micelles versus alcohol-based hand sanitizers was performed, and their safety profiles were also assessed. It was demonstrated that rhamnolipid nano-micelles had a comparable antibacterial activity to alcohol-based hand sanitizer, with a better safety profile, i.e., rhamnolipid nano-micelles are unlikely to cause any harmful effects on the skin. Thus, rhamnolipid nano-micelles could be recommended to replace alcohol-based hand sanitizers; however, they must still be tested by healthcare workers in healthcare settings to ascertain their antimicrobial activity and safety.