Infectious diseases are the leadingcauses of death worldwide, with bacterialinfections giving substantially to thehigh rate of mortality. With the first case in theUnited States, a person carrying a ‘superbug’, an E. coli bacteria strainresistant to antibiotics of last resort, it becomes apparent that alternative strategies are urgently needed to combat bacterial infections.Bactericidal nano-particles can give a viable alternative to current antibiotictherapies. The development of bactericidal nano-particles need rational designof the particle, an efficient synthetic approach, and understanding oftheir biocompatibility and toxicity.

Understandingbacterial pathogenesis give another key to bacterial inhibition withoutaltering gut microbiome or making undesirable bacterial resistance214. Among the emerging antibacterial particles,NDs have been tested in combination with carbohydrates, proteins, andantibiotics, with very recent exciting application of ND-Gutta percha-amoxicillin composite as a tooth rootcanal filler that is in clinical trials now. Different protocolsto modify the ND surface followed by grafting of antimicrobial therapeuticshave been studied.

However, the use of ND is not limited toits role as acarrier of antibacterial therapeutics. Surprisingly, ND itself may inducebacterial death. Below we examine the ND potential in protecting bacterialinfections with emphasis on uropathogenic infections. In spite of extensive in vivo and invitro studies conductedwith ND derivatives using eukaryotic cells, only a handful of studies have beenpublished on ND toxicity toward prokaryotic cells. On the contrary, interactions of other carbonaceous materialswith bacteria have been extensively studied. Crucial characteristics ofgraphene-based materials, CNT, and fullerenes, such as dispersibility, size,and oxidation capability have been estimatedwith regard to bacterial toxicity215. ND arise as a toxic nanomaterial towardGram-negative Escherichia coli and Gram-positive Bacillus subtilis strains. The authors proposedthat the antibacterial ND activity is likely connected to the reactive oxygen-containing groups on the ND surface,although more studies are required to support this proposition.

It is likelythe ND antibacterial properties, similarly to other carbon materials, are related to: (i) direct attachment to the bacterial wall throughthe surface groups (i.e. charge interaction, hydrogen bonds), (ii) membrane stress (physical damage of the membrane), (iii) inhibition of metabolic processes (i.e.

inability to produce antioxidants in response tooxidative stress).Uropathogenic E. coli(UPEC) Gram-negative bacteria is responsible for 90% ofurinary tract infections (UTIs). In spite of numerous defensive mechanisms ofthe innate immune system (production of antimicrobial factors, cytokinetriggered recruitment of neutrophils followed by exfoliation of superficial infected tissue), some bacteria last undeterred even after antibiotic treatment hidden in inter-cellularreservoirs of bladder epithelial cells (BECs)216. Nanodiamond may provide an interesting opportunityto rupture BEC membranes followed by their exfoliation due to its superiorhardness and large number of sharp edges (HPHTND), which was described to facilitate its transportthrough cell membrane with subsequent fast endosomalescape217. UPEC foundation in the bladder heavily reliesupon type I pili virulence factor, FimH, which binds to uroplakin mannosylated proteins on the surfaceof BECs. Thus, a possible line of defenseis focused on protecting UPEC adherence to the bladder cells.

Mannose moleculesvery strongly adhere to FimH lectin. Although monosaccharides possess low affinity to FimH, multivalent mannoseligands provide high strength of binding for FimH lectin. However,synthetic protocols toward multi-valent mannose ligands are sometimes tooelaborative.

Recently, a new way of integration of polymannose ligands onto the ND surface has been proposed viaphotoactivation of ND-tetrafluoroazide leading to aND-nitrene radical that reacts withsugar molecules through C-H insertion. Preserved activity of sugar units afterthe reaction with nitrenes was demonstrated by effective binding of ND-glycansto plant fluorescent lectins218


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