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

Nie, Dan; Hu, Yinling; Zhou, Chen; Li, Mingkai; Zheng, Hui; Luo, Xiaoxing; Mao, Xinggang; Xue, Xiaoyan

doi:10.1186/s12929-020-0617-7

Cited by 181 publications

(152 citation statements)

References 91 publications

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“…SuOMV, sOMV, and nOMV had different zeta potential, which may also be associated with their potency to induce different levels of immune response. OmpA was found to be a predominant virulence factor which plays key roles in regulating the adhesion, aggressiveness, and biofilm formation of A. baumannii (61,62). The highest level of OmpA-specific IgG was observed in mice vaccinated with SuOMV, though the highest percentage of OmpA was included in sOMV.…”

Section: Discussionmentioning

confidence: 99%

Development of Different Methods for Preparing Acinetobacter baumannii Outer Membrane Vesicles Vaccine: Impact of Preparation Method on Protective Efficacy

Sun

Chen

et al. 2020

Front. Immunol.

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Acinetobacter baumannii (A. baumannii) is becoming a common global concern due to the emergence of multi-drug or pan-drug resistant strains. Confronting the issue of antimicrobial resistance by developing vaccines against the resistant pathogen is becoming a common strategy. In this study, different methods for preparing A. baumannii outer membrane vesicles (AbOMVs) vaccines were developed. sOMV (spontaneously released AbOMV) was extracted from the culture supernatant, while SuOMV (sucrose-extracted AbOMV) and nOMV (native AbOMV) were prepared from the bacterial cells. Three AbOMVs exhibited significant differences in yield, particle size, protein composition, and LPS/DNA content. To compare the protective efficacy of the three AbOMVs, groups of mice were immunized either intramuscularly or intranasally with each AbOMV. Vaccination via both routes conferred significant protection against lethal and sub-lethal A. baumannii challenge. Moreover, intranasal vaccination provided more robust protection, which may be attributed to the induction of significant sIgA response in mucosal sites. Among the three AbOMVs, SuOMV elicited the highest level of protective immunity against A. baumannii infection, whether intramuscular or intranasal immunization, which was characterized by the expression of the most profound specific serum IgG or mucosal sIgA. Taken together, the preparation method had a significant effect on the yield, morphology, and composition of AbOMVs, that further influenced the protective effect against A. baumannii infection.

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Section: Discussionmentioning

confidence: 99%

Development of Different Methods for Preparing Acinetobacter baumannii Outer Membrane Vesicles Vaccine: Impact of Preparation Method on Protective Efficacy

Sun

Chen

et al. 2020

Front. Immunol.

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“…Outer membrane proteins play an important role in the survival, drug resistance, and pathogenicity of A. baumannii [ 22 ]. Deletion or mutation of key outer membrane proteins can seriously affect the survival and pathogenicity of A. baumannii [ 23 ]. Okada et al [ 17 ] confirmed that the MacA-MacB-TolC tripartite complex is a transmembrane machine and can actively extrude substrates, including macrolide antibiotics, virulence factors, peptides, and cell envelope precursors.…”

Section: Discussionmentioning

confidence: 99%

Antigen Epitope Developed Based on Acinetobacter baumannii MacB Protein Can Provide Partial Immune Protection in Mice

Song

Zhao

Ding

2020

BioMed Research International

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Acinetobacter baumannii (A. baumannii) is an important opportunistic pathogen widely present in medical environment. Given its complex drug resistance, A. baumannii poses a serious threat to the safety of critically ill patients. Given the limited alternative antibiotics, nonantibiotic-based functional anti-A. baumannii infection proteins must be developed. In this study, we firstly used a series of biological software to predict potential epitopes in the MacB protein sequence and verified them by antibody recognition and lymphocyte proliferation tests. We finally screened out B cell epitope 2, CD8+ T cell epitope 7, and CD4+ T cell epitope 11 and connected them to construct a recombinant antigen epitope (RAE). The determination of IgG in the serum of immunised mice and cytokines in the supernatant of lymphocytes showed that the constructed epitope induced an immune response mediated by Th-1 cells. Finally, the challenge experiment of A. baumannii infection in mice confirmed that the epitope developed based on MacB, especially RAE, provided incomplete immune protection for mice.

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“…It is believed that this approach reduces the bacteria’s ability to evade the host’s immune system, allowing more time to clear the infection [ 96 ]. Nie et al have written a timely review discussing non-antibiotic options for OmpA inhibition of MDR infections [ 97 ].…”

Section: Porinsmentioning

confidence: 99%

Overcoming Intrinsic and Acquired Resistance Mechanisms Associated with the Cell Wall of Gram-Negative Bacteria

et al. 2020

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The global increase in multi-drug-resistant bacteria is severely impacting our ability to effectively treat common infections. For Gram-negative bacteria, their intrinsic and acquired resistance mechanisms are heightened by their unique cell wall structure. The cell wall, while being a target of some antibiotics, represents a barrier due to the inability of most antibacterial compounds to traverse and reach their intended target. This means that its composition and resulting mechanisms of resistance must be considered when developing new therapies. Here, we discuss potential antibiotic targets within the most well-characterised resistance mechanisms associated with the cell wall in Gram-negative bacteria, including the outer membrane structure, porins and efflux pumps. We also provide a timely update on the current progress of inhibitor development in these areas. Such compounds could represent new avenues for drug discovery as well as adjuvant therapy to help us overcome antibiotic resistance.

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

Cited by 181 publications

References 91 publications

Development of Different Methods for Preparing Acinetobacter baumannii Outer Membrane Vesicles Vaccine: Impact of Preparation Method on Protective Efficacy

Development of Different Methods for Preparing Acinetobacter baumannii Outer Membrane Vesicles Vaccine: Impact of Preparation Method on Protective Efficacy

Antigen Epitope Developed Based on Acinetobacter baumannii MacB Protein Can Provide Partial Immune Protection in Mice

Overcoming Intrinsic and Acquired Resistance Mechanisms Associated with the Cell Wall of Gram-Negative Bacteria

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