Despite the wide success of antibiotics in modern medicine, the treatment of bacterial infections still faces critical challenges, especially due to the rapid emergence of antibiotic resistance. As a result, local antimicrobial treatment aimed at enhancing drug concentration at the site of infection while avoiding systemic exposure is becoming increasingly attractive, as it may alleviate resistance development. Meanwhile, therapeutic nanoparticles, especially liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles, are gaining traction to improve the therapeutic efficacy with many applications specifically focused on local antimicrobial treatment. This review highlights topics where nanoparticle-based strategies hold significant potential to advance treatment against local bacterial infections, including (1) promoting antibiotic localization to the pathogen, (2) modulating drug-pathogen interaction against antibiotic resistance, and (3) enabling novel anti-virulence approaches for 'drug-free' antimicrobial activity. In each area, we highlight the innovative antimicrobial strategies tailored for local applications and review the progress made for the treatment of bacterial infections.

With the rapid advancement of robotic research, it becomes increasingly interesting and important to develop biomimetic micro-or nanorobots that translate biological principles into robotic systems. We report the design, construction, and evaluation of a dual-cell membrane-functionalized nanorobot for multipurpose removal of biological threat agents, particularly concurrent targeting and neutralization of pathogenic bacteria and toxins. Specifically, we demonstrated ultrasound-propelled biomimetic nanorobots consisting of gold nanowires cloaked with a hybrid of red blood cell (RBC) membranes and platelet (PL) membranes. Such hybrid cell membranes have a variety of functional proteins associated with human RBCs and PLs, which give the nanorobots a number of attractive biological capabilities, including adhesion and binding to PL-adhering pathogens (e.g., Staphylococcus aureus bacteria) and neutralization of pore-forming toxins (e.g., -toxin). In addition, the biomimetic nanorobots displayed rapid and efficient prolonged acoustic propulsion in whole blood, with no apparent biofouling, and mimicked the movement of natural motile cells. This propulsion enhanced the binding and detoxification efficiency of the robots against pathogens and toxins. Overall, coupling these diverse biological functions of hybrid cell membranes with the fuel-free propulsion of the nanorobots resulted in a dynamic robotic system for efficient isolation and simultaneous removal of different biological threats, an important step toward the creation of a broad-spectrum detoxification robotic platform.

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The number of vertebrae is an economically important trait that affects carcass length and meat production in pigs. A major quantitative trait locus (QTL) for thoracic vertebral number has been repeatedly identified on pig chromosome (SSC) 7. To dissect the genetic basis of the major locus, we herein genotyped a large sample of animals from 3 experimental populations of Chinese and Western origins using 60K DNA chips. Genome-wide association studies consistently identified the locus across the 3 populations and mapped the locus to a 947-Kb region on SSC7. An identical-by-descent sharing assay refined the locus to a 100-Kb segment that harbors only two genes including VRTN and SYNDIG1L. Of them, VRNT has been proposed as a strong candidate of the major locus in Western modern breeds. Further, we resequenced the VRTN gene using DNA samples of 35 parental animals with known QTL genotypes by progeny testing. Concordance tests revealed 4 candidate causal variants as their genotypes showed the perfect segregation with QTL genotypes of the tested animals. An integrative analysis of evolutional constraints and functional elements supported two VRTN variants in a complete linkage disequilibrium phase as the most likely causal mutations. The promising variants significantly affect the number of thoracic vertebrae (one vertebra) in large scale outbred animals, and are segregating at rather high frequencies in Western pigs and at relatively low frequencies in a number of Chinese breeds. Altogether, we show that VRTN variants are significantly associated with the number of thoracic vertebrae in both Chinese and Western pigs. The finding advances our understanding of the genetic architecture of the vertebral number in pigs. Furthermore, our finding is of economical importance as it provides a robust breeding tool for the improvement of vertebral number and meat production in both Chinese indigenous pigs and Western present-day commercial pigs.

Anti‐adhesion therapies interfere with the bacterial adhesion to the host and thus avoid direct disruption of bacterial cycles for killing, which may alleviate resistance development. Herein, an anti‐adhesion nanomedicine platform is made by wrapping synthetic polymeric cores with bacterial outer membranes. The resulting bacterium‐mimicking nanoparticles (denoted “OM‐NPs”) compete with source bacteria for binding to the host. The “top‐down” fabrication of OM‐NPs avoids the identification of the adhesins and bypasses the design of agonists targeting these adhesins. In this study, OM‐NPs are made with the membrane of Helicobacter pylori and shown to bind with gastric epithelial cells (AGS cells). Treatment of AGS cells with OM‐NPs reduces H. pylori adhesion and such anti‐adhesion efficacy is dependent on OM‐NP concentration and its dosing sequence.

The efforts of detecting bioactive targets with complex, dynamic, and unknown molecular profiles have inspired the development of various biosensor platforms. Herein, we report a cell-membrane-modified field effect transistor (FET) as a function-based nanosensor for the detection and quantitative measurement of numerous toxins and biological samples. By coating carbon nanotube FETs with natural red blood cell membranes, the resulting biomimetic nanosensor can selectively interact with and absorb broad-spectrum hemolytic toxins regardless of their molecular structures. Toxin–biomembrane interactions alter the local charge distribution at the FET surface in an ultrasensitive and concentration-dependent manner, resulting in a detection limit down to the femtomolar (fM) range. Accurate and quantitative measurements are enabled via a built-in calibration mechanism of the sensor, which overcomes batch-to-batch fabrication variations, and are demonstrated using three distinct toxins and various complex bacterial supernatants. The measured signals of bacterium-secreted proteins correlate linearly with the actual bacterial numbers, making the biosensor a nontraditional approach to rapidly detecting bacterial concentrations without a need to count bacterial colonies.

Neutralization of bacterial toxins has become a compelling approach to treating bacterial infections as it may pose less selective pressure for the development of bacterial resistance. Currently, the majority of toxin neutralization platforms act by targeting the molecular structure of the toxin, which requires toxin identification and customized design for different diseases. Therefore, their development has been challenged by the enormous number and complexity of bacterial toxins. Herein, biomimetic toxin nanosponges are formulated by coating membranes of human red blood cells (hRBCs) onto polymeric nanoparticles, which act as a toxin decoy to absorb and neutralize a broad-spectrum of hemolytic toxins regardless of their molecular structure. When tested with model pore-forming toxins, including melittin, α-hemolysin of methicillin-resistant Staphylococcus aureus, listeriolysin O of Listeria monocytogenes, and streptolysin O of Group A Streptococcus, the hRBC nanosponges are able to completely inhibit toxin-induced hemolysis in a concentration-dependent manner. In addition, the nanosponge-detained toxins show no cytotoxicity when tested on human umbilical vein endothelial cells and no lethality when injected into mice, which together indicate effective toxin neutralization. Overall, these results demonstrate the broad applicability and high effectiveness of the hRBC nanosponges as a novel antivirulence platform against hemolytic toxins from various strains of bacteria.