The lack of bacterial-targeting function in antibiotics and their prophylactic usage have caused overuse of antibiotics, which lead to antibiotic resistance and inevitable long-term toxicity. To overcome these issues, we develop neutrophil-bacterial hybrid cell membrane vesicle (HMV)–coated biofunctional lipid nanoparticles (LNP@HMVs), which are designed to transport antibiotics specifically to bacterial cells at the infection site for the effective treatment and prophylaxis of bacterial infection. The dual targeting ability of HMVs to inflammatory vascular endothelial cells and homologous Gram-negative bacterial cells results in targeted accumulation of LNP@HMVs in the site of infections. LNP@HMVs loaded with the antibiotic norfloxacin not only exhibit enhanced activity against planktonic bacteria and bacterial biofilms in vitro but also achieve potent therapeutic efficacy in treating both systemic infection and lung infection. Furthermore, LNP@HMVs trigger the activation of specific humoral and cellular immunity to prevent bacterial infection. Together, LNP@HMVs provide a promising strategy to effectively treat and prevent bacterial infection.

The emergence of multidrug-resistant bacteria presents a severe threat to public health and causes extensive losses in livestock husbandry and aquaculture. Effective strategies to control such infections are highly demanded. Enhancing host immunity is an ideal strategy with less side-effects than antibiotics. To explore any metabolite candidates, we applied metabolomic approach to investigate the metabolic profiles of mice after Klebsiella pneumoniae infection. Compared to the mice comprised to K. pneumoniae infection, the mice survived from the infection displayed an elevated level of L-valine. Our further analysis showed that L-valine increased phagocytosis of macrophages, thereby reducing the load of pathogens not limited to K. pneumoniae but also E. coli clinical isolates in infected tissues. Two mechanisms are involved: L-valine activates the PI3K/Akt1, and promotes NO production through inhibition of arginase activity. The NO precursor, L-arginine, is necessary for the phagocytosis of L-valine-stimulated macrophages. Valine-arginine combination therapy has a stronger ability in killing K. pneumoniae and presents the similar effect in other Gram-negative bacteria (E. coli, Pseudomonas aeruginosa) and Gram-positive bacterium (Staphylococcus aureus). Our study extends the role of metabolism in innate immunity and develops the possibility of employing the metabolic modulator-mediated innate immunity as a therapy for bacterial infections.

Infections caused by antibiotic-resistant bacteria (ARB) are one of the major global health challenges of our time. In addition to developing new antibiotics to combat ARB, sensitizing ARB, or pursuing alternatives to existing antibiotics are promising options to counter antibiotic resistance. This review compiles the most promising anti-ARB strategies currently under development. These strategies include the following: (i) discovery of novel antibiotics by modification of existing antibiotics, screening of small-molecule libraries, or exploration of peculiar places; (ii) improvement in the efficacy of existing antibiotics through metabolic stimulation or by loading a novel, more efficient delivery systems; (iii) development of alternatives to conventional antibiotics such as bacteriophages and their encoded endolysins, anti-biofilm drugs, probiotics, nanomaterials, vaccines, and antibody therapies. Clinical or preclinical studies show that these treatments possess great potential against ARB. Some anti-ARB products are expected to become commercially available in the near future.

Background: Heat shock proteins (Hsps) perform a fundamental role in protecting plants against abiotic stresses. Although researchers have made great efforts on the functional analysis of individual family members, Hsps have not been fully characterized in rice (Oryza sativaL.) and little is known about their interactors.Results: In this study, we combined orthology-based approach with expression association data to screen rice Hsps for the expression patterns of which strongly correlated with that of heat responsive probe-sets. Twenty-seven Hsp candidates were identified, including 12 small Hsps, six Hsp70s, three Hsp60s, three Hsp90s, and three clpB/Hsp100s. Then, using a combination of interolog and expression profile-based methods, we inferred 430 interactors of Hsp70s in rice, and validated the interactions by co-localization and function-based methods. Subsequent analysis showed 13 interacting domains and 28 target motifs were over-represented in Hsp70s interactors. Twenty-four GO terms of biological processes and five GO terms of molecular functions were enriched in the positive interactors, whose expression levels were positively associated with Hsp70s. Hsp70s interaction network implied that Hsp70s were involved in macromolecular translocation, carbohydrate metabolism, innate immunity, photosystem II repair and regulation of kinase activities.Conclusions: Twenty-seven Hsps in rice were identified and 430 interactors of Hsp70s were inferred and validated, then the interacting network of Hsp70s was induced and the function of Hsp70s was analyzed. Furthermore, two databases named Rice Heat Shock Proteins (RiceHsps) and Rice Gene Expression Profile (RGEP), and one online tool named Protein-Protein Interaction Predictor (PPIP), were constructed and could be accessed athttp://bioinformatics.fafu.edu.cn/.

Significance: Staphylococcus aureusinvariably acquires resistance mechanisms against new antibiotics. The persistent colonization withS. aureusis the key risk factor for invasive disease and a driver for the evolution of antibiotic resistant isolates. Anti-S. aureusantibodies that could promote decolonization, prevent infection, or treat disease would alleviate the selection for drug resistance. The successful development of such antibodies is complicated by Staphylococcal protein A (SpA) in the envelope ofS. aureus. SpA captures immunoglobulins via their constant region, preventing antibodies from initiating anti-staphylococcal activities. Here, we demonstrate that therapeutic anti-S. aureusantibodies can be engineered to avoid sequestration by SpA. Such antibodies display extended half-lives and improve bacterial uptake and killing by immune cells.