Anti-outer Membrane Vesicle Antibodies Increase Antibiotic Sensitivity of Pan-Drug-Resistant Acinetobacter baumannii

Abstract

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 .

Integrative analysis of outer membrane vesicles proteomics and whole-cell transcriptome analysis of eravacycline induced Acinetobacter baumannii strains

“…OMVs of both A. baumannii ATCC 19606 and JU0126 were prepared from previously described methods [70,71]. In brief, the eravacycline treated and untreated Acinetobacter baumannii were grown in 500 ml Luria Bertani (LB) broth until the OD at 600 nm reached 1.0 at 37°C in incubator shaker with (sub-MIC concentration achieved upon induction of resistance) eravacycline, that is 8 μg/ml for A. baumannii ATCC 19606 strain and 32 μg/ml for A. baumannii JU0126 strain) and without eravacycline.…”

<p>Proteomic Applications in Antimicrobial Resistance and Clinical Microbiology Studies</p>

“…Therefore, antibodies that acted against the known OM proteins were utilized to show antibody-combating bacterial growth. 182 As the results showed anti-TolC had highly significant inhibition on bacterial growth in medium with CAP. This highlights a potential novel method to treat infection by antibiotic-resistant bacteria.…”

Outer membrane protein A (OmpA) as a potential therapeutic target for Acinetobacter baumannii infection

“…With the emergence of MDR, XDR and pan-drugresistant A. baumannii [92,93], the traditional therapies have already failed to defeat complex infections caused by these pathogens. It is urgent to find new methods for treating drug-resistant A. baumannii infection.…”