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Metal and metal oxide nanoparticles (NPs) have been increasingly utilized in many industries to harness their documented antibacterial properties. However, the mechanism(s) of action is still debated in the literature. The aim of this study is to understand how changes in outer membrane charge of a test bacteria Haemophilus influenzae alter the antibacterial activity of ZnO NPs of average sizes of 20 nM and 60 nM. H. influenzae outer membrane charge was altered through use of the wild strain (Rd) and mutant lines H543 and H446. Results indicate that antibacterial effects are both concentration and size dependent, with smaller NPs causing increased antibacterial response. Most critically, antibacterial assays and collected TEM images demonstrate that increasing negative charge on the outer membrane of bacteria decreased the antibacterial activity of the ZnO NPs. Finally, this work demonstrates the possibility of using ZnO NPs to treat H. influenzae infection in clinical settings.

At present, including failed attempts, it takes about 15 years and costs totaling up to $2.6 billion to take a promising new compound from laboratory to the market. Increasing drug resistance among microbial pathogens has led to a growing interest in exploring novel methods to enhance the efficacy of existing drugs. Combination therapies involving two or more known antimicrobial methods, particularly those involving nanoparticles for combating the clinical problems associated with antibiotic resistance, have been garnering interest. In the current study, we determined whether a combination therapy involving silver nanoparticles, which are known for their antimicrobial activity, and the widely used antibiotic ampicillin can be effective against methicillin-resistant Staphylococcus aureus (MRSA). In the presence of sub-lethal dose of silver nanoparticles, ampicillin was found to be effective against MRSA. Indeed, the results show that silver nanoparticles and ampicillin act synergistically, with the effect being more pronounced when a lower concentration of ampicillin is present. When present at a higher concentration, ampicillin coats the silver nanoparticle, preventing the direct interaction of nanoparticles and bacteria. This study discusses the possible applications of combination antimicrobial therapies involving silver nanoparticles for therapeutic treatments.