An Antibacterial Nanorobotic Approach for the Specific Targeting and Removal of Multiple Drug‐Resistant Staphylococcus aureus

Abstract

deaths were reported out of 120 000 S. aureus infections in 2017. The reasons for the higher rate of MRSA infection and its associated deaths are due to the rapid development of tolerance/resistance to multiple antibiotics drugs (multiple drug resistance, MDR), [5] and the quick adaptability of S. aureus to the host environment via evading the immune system and residing as a persister inside the host cells. Persisters are the cause of secondary and chronic infection with enhanced pathogenesis and resistance, therefore, MRSA persisters are known to be extremely difficult to treat with current antibiotics. [6] Based on these facts, it is conceivable that new resistance-free antibiotics or antistaphylococcal therapies are required not only to cure the lethal MDR MRSA infections but also to bypass the development and dissemination of antibiotic-resistance to avoid the future outbreak of MDR bacterial pathogen infectious disease. [7] In this context, various antistaphylococcal strategies such as antimicrobial peptides (AMPs), [8] enzybiotics, [9] antivirulence agents, [10] gene editing enzymes, [11] bacteriophages, [12] and nanoparticles (NPs) [13,14] are being developed as alternative therapeutic options to antibiotics. Although AMPs, antivirulence agents, or bacteriophages have produced promising results as therapeutic agents yet the development of resistance against Methicillin-resistant Staphylococcus aureus (MRSA) causes diseases ranging from skin infections to lethal sepsis and has become a serious threat to human health due to multiple-drug resistance (MDR). Therefore, a resistance-free antibacterial therapy is necessary to overcome MDR MRSA infections. In this study, an antibacterial nanorobot (Ab-nanobot) is developed wherein a cell wall-binding domain (CBD)-endolysin, acting as a sensor, is covalently conjugated with an actuator consisting of an iron oxide/silica core-shell. The CBD-endolysin sensor shows an excellent specificity to detect, bind, and accumulate on the S. aureus USA300 cell surface even in a bacterial consortium, and in host cell infections. Ab-nanobot specifically captures and kills MRSA in response to medically approved radiofrequency (RF) electromagnetic stimulation (EMS) signal. When Ab-nanobot receives the RF-EMS signal on the cell surface, actuator induces cell death in MRSA with 99.999% removal within 20 min by cell-wall damage via generation of localized heat and reactive oxygen species. The in vivo efficacy of Ab-nanobot is proven using a mice subcutaneous skin infection model. Collectively, this study offers a nanomedical resistance-free strategy to overcome MDR MRSA infections by providing a highly specific nanorobot for S. aureus.

EGCG-Mediated Potential Inhibition of Biofilm Development and Quorum Sensing in Pseudomonas aeruginosa

“…Mixed infection of P. aeruginosa and S. aureus increases patient morbidity [ 24 ]. Various anti-staphylococcal strategies such as antimicrobial peptides (AMPs), enzybiotics, antivirulence agents, gene editing enzymes, bacteriophages, and nanoparticles (NPs) are being developed as alternative therapeutic options to antibiotics [ 25 ]. Modifying the chemical structure of an antimicrobial agent and synthesis, new compounds for inhibiting resistant mechanisms to antibiotics is also a novel method to exploit new antibacterial agents [ 26 ].…”

Surface Polarity-Insensitive Organosilicasome-Based Clustering of Nanoparticles with Intragap Distance Tunability

“…Multimodal imaging with tunable optical enhancement and quenching could be demonstrated as the distances between NPs were controlled in the nanoclusters. We expect that the unprecedented morphologies of the nanoclusters shown by our results will advance the understanding of the assembly of nanomaterials and expand the range of applications of nanomaterials. − , …”

“…We expect that the unprecedented morphologies of the nanoclusters shown by our results will advance the understanding of the assembly of nanomaterials and expand the range of applications of nanomaterials. [50][51][52][53][54][55][56][57][58][59][60][61]64 4. EXPERIMENTAL SECTION Materials.…”

Nanophysical Antimicrobial Strategies: A Rational Deployment of Nanomaterials and Physical Stimulations in Combating Bacterial Infections

“…Recently, Batool et al designed an antibacterial nanobot (Ab-nanobot) by covalently conjugating a cell wall-binding domain (CBD)endolysin with an actuator of Fe 3 O 4 /SiO 2 with a core-shell nanostructure. [121] The CBD-endolysin modification conferred the Ab-nanobot-specific binding and bacteria-accumulation ability. Under exposure to RF-EMS signals, Ab-nanobots generated localized heat and reacted with hydrogen peroxide (a by-product of cell metabolism) to produce toxic •OH.…”