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Acinetobacter baumannii often causes serious nosocomial infections. Because of its serious drug resistance problems, complex drug resistance mechanism, and rapid adaptation to antibiotics, it often shows pan-drug resistance and high fatality rates, which represent great challenges for clinical treatment. Therefore, identifying new ways to overcome antibiotic resistance is particularly important. In this study, mice immunized with A. baumannii outer membrane vesicles (AbOMVs) produced high IgG levels for a long time, and this antiserum significantly increased the small molecule intracellular aggregation rate and concentrations. In vitro experiments demonstrated that the combined used of anti-AbOMV serum and quinolone antibiotics significantly increased the sensitivity of the bacteria to these antibiotics. Mouse sepsis model experiments demonstrated that delivery of these antibodies using both active and passive immunization strategies significantly improved the susceptibility to quinolone antibiotics, improved the survival rate of mice infected with A. baumannii , and reduced the bacterial load in the organs. In a pneumonia model, the combination of serum anti-AbOMVs and levofloxacin improved levofloxacin sensitivity, which significantly reduced the bacterial loads in the lung and spleen compared with those of the antibiotic or antibody alone. This combination also significantly reduced lung inflammatory cell infiltration and inflammatory cytokine aggregation. In this study, the main protein targets that bound to these antibodies were identified. Structural modeling showed that seven of the proteins were porins. Therefore, we speculated that the anti-AbOMV antibodies mainly improved the intracellular aggregation of antibiotics by affecting porins, thus improving susceptibility to quinolone antibiotics. This study provides a method to improve susceptibility to existing antibiotics and a novel idea for the prevention and treatment of pan-drug-resistant A. baumannii .

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T cell activation‐induced cell death (AICD) during tumor pathogenesis is a tumor immune escape process dependent on dendritic cells (DCs). Proper immune‐modulatory therapies effectively inhibit tumor‐specific CD8+ T cell exhaustion and enhance antitumor immune responses. Here, high‐pressure homogenization is utilized to drive immunomodulator IL10‐modified bacteria to extrude through the gap and self‐assemble into bacterial biomimetic vesicles exposing IL10 (IL10‐BBVs) on the surface with high efficiency. IL10‐BBVs efficiently target DCs in tumor‐draining lymph nodes and thus increase the interaction between IL10 on BBVs and IL10R on DCs to suppress AICD and mitigate CD8+ T cell exhaustion specific to tumor antigens. Two subcutaneous peripheral injections of IL10‐BBVs 1 week apart in tumor‐bearing mice effectively increase systemic and intratumoral proportions of CD8+ T cells to suppress tumor growth and metastasis. Tumor‐specific antigen E7 is enclosed into the periplasm of IL10‐BBVs (IL10‐E7‐BBVs) to realize concurrent actions of the immunomodulator IL10 and the tumor antigen human papillomavirus (HPV) 16E7 in lymph nodes, further enhancing the antitumor effects mediated by CD8+ T cells. The development of this modified BBV delivery platform will expand the application of bacterial membranes and provide novel immunotherapeutic strategies for tumor treatment.

The disease caused by SARS-CoV-2 infection threatens human health. In this study, we used high-pressure homogenization technology not only to efficiently drive the bacterial membrane to produce artificial vesicles but also to force the fusion protein ClyA-receptor binding domain (RBD) to pass through gaps in the bacterial membrane to increase the contact between ClyA-RBD and the membrane. Therefore, the load of ClyA-RBD on the membrane is substantially increased. Using this technology, we constructed a “ring-like” bacterial biomimetic vesicle (BBV) loaded with polymerized RBD (RBD-BBV). RBD-BBVs injected subcutaneously can accumulate in lymph nodes, promote antigen uptake and processing, and elicit SARS-CoV-2-specific humoral and cellular immune responses in mice. In conclusion, we evaluated the potential of this novel bacterial vesicle as a vaccine delivery system and provided a new idea for the development of SARS-CoV-2 vaccines.