Acinetobacter baumannii Outer Membrane Vesicles Elicit a Potent Innate Immune Response via Membrane Proteins

Jun, So Hyun; Lee, Jung Hwa; Kim, Bo Ra; Kim, Kyung Sik; Park, Tae In; Lee, Je Chul; Lee, Yoo Chul

doi:10.1371/journal.pone.0071751

Cited by 113 publications

(86 citation statements)

References 34 publications

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“…Proteomic analysis of A. baumannii OMVs revealed the presence of more than 130 proteins including: AbOmpA, serine-as well as Zn-dependent proteases, phospholipases, bacterioferritin, Cu/Zn superoxide dismutase, catalase, and ferrichrome-iron receptor [30]. Further data published by Jun and co-workers demonstrated considerable role of A. baumannii OMVs in stimulation of innate immune response that may contribute to immunopathology of the infected host [31]. Another group of A. baumannii VF include phospholipases.…”

Section: Virulence Factorsmentioning

confidence: 92%

Acinetobacter baumannii: biology and drug resistance — role of carbapenemases

Nowak

Paluchowska

2015

Folia Histochem Cytobiol.

107

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Acinetobacter baumannii is a Gram-negative, glucose-non-fermenting, oxidase-negative coccobacillus, most commonly associated with the hospital settings. The ability to survive in adverse environmental conditions as well as high level of natural and acquired antimicrobial resistance make A. baumannii one of the most important nosocomial pathogens. While carbapenems have long been considered as antimicrobials of last-resort, the rates of clinical A. baumannii strains resistant to these antibiotics are increasing worldwide. Carbapenem resistance among A. baumannii is conferred by coexisting mechanisms including: decrease in permeability of the outer membrane, efflux pumps, production of beta-lactamases, and modification of penicillin-binding proteins. The most prevalent mechanism of carbapenem resistance among A. baumannii is associated with carbapenem-hydrolysing enzymes that belong to Ambler class D and B beta-lactamases. In addition, there have also been reports of resistance mediated by selected Ambler class A carbapenemases among A. baumannii strains. Resistance determinants in A. baumannii are located on chromosome and plasmids, while acquisition of new mechanisms can be mediated by insertion sequences, integrons, transposons, and plasmids. Clinical relevance of carbapenem resistance among strains isolated from infected patients, carriers and hospital environment underlines the need for carbapenemase screening. Currently available methods vary in principle, accuracy and efficiency. The techniques that deserve particular attention belong to both easily accessible unsophisticated methods as well as advanced techniques based on mass spectrometry or molecular biology. While carbapenemases limit the therapeutic options in A. baumannii infections, studies concerning novel beta-lactamase inhibitors offer a new insight into effective therapy.

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Section: Virulence Factorsmentioning

confidence: 92%

Acinetobacter baumannii: biology and drug resistance — role of carbapenemases

Nowak

Paluchowska

2015

Folia Histochem Cytobiol.

107

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“…Furthermore, OmpA has been suggested to be involved in the biogenesis of OMVs (104). OMVs from Acinetobacter may have an important role in the development of novel therapeutics, as they can stimulate a strong immune response and are protective when administered as a vaccine (105)(106)(107).…”

Section: Protein Secretionmentioning

confidence: 99%

Pathogenic Acinetobacter: from the Cell Surface to Infinity and Beyond

2016

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The genus Acinetobacter encompasses multiple nosocomial opportunistic pathogens that are of increasing worldwide relevance because of their ability to survive exposure to various antimicrobial and sterilization agents. Among these, Acinetobacter baumannii, Acinetobacter nosocomialis, and Acinetobacter pittii are the most frequently isolated in hospitals around the world. Despite the growing incidence of multidrug-resistant Acinetobacter spp., little is known about the factors that contribute to pathogenesis. New strategies for treating and managing infections caused by multidrug-resistant Acinetobacter strains are urgently needed, and this requires a detailed understanding of the pathobiology of these organisms. In recent years, some virulence factors important for Acinetobacter colonization have started to emerge. In this review, we focus on several recently described virulence factors that act at the bacterial surface level, such as the capsule, O-linked protein glycosylation, and adhesins. Furthermore, we describe the current knowledge regarding the type II and type VI secretion systems present in these strains.

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“…OMVs from Acinetobacter baumannii induce cytokine secretion in epithelial cells [48], Clostridium perfringens OMVs stimulate the murine macrophage cell line RAW264.7 to produce G-CSF, TNF-α, and IL-6 [6]. L. pneumophila also produces OMVs that can be taken up by macrophages and furthermore induce tissue damage in human lung tissue explants [23].…”

Section: Discussionmentioning

confidence: 99%

Legionella pneumophila-derived outer membrane vesicles promote bacterial replication in macrophages

Jung

Stoiber

Herkt

et al. 2016

3.2 Airway Cell Biology and Immunopathology

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The formation and release of outer membrane vesicles (OMVs) is a phenomenon of Gramnegative bacteria. This includes Legionella pneumophila (L. pneumophila), a causative agent of severe pneumonia. Upon its transmission into the lung, L. pneumophila primarily infects and replicates within macrophages. Here, we analyzed the influence of L. pneumophila OMVs on macrophages. To this end, differentiated THP-1 cells were incubated with increasing doses of Legionella OMVs, leading to a TLR2-dependent classical activation of macrophages with the release of pro-inflammatory cytokines. Inhibition of TLR2 and NF-κB signaling reduced the induction of pro-inflammatory cytokines. Furthermore, treatment of THP-1 cells with OMVs prior to infection reduced replication of L. pneumophila in THP-1 cells. Blocking of TLR2 activation or heat denaturation of OMVs restored bacterial replication in the first 24 h of infection. With prolonged infection-time, OMV pre-treated macrophages became more permissive for bacterial replication than untreated cells and showed increased numbers of Legionella-containing vacuoles and reduced pro-inflammatory cytokine induction. Additionally, miRNA-146a was found to be transcriptionally induced by OMVs and to facilitate bacterial replication. Accordingly, IRAK-1, one of miRNA-146a's targets, showed prolonged activation-dependent degradation, which rendered THP-1 cells more permissive for Legionella replication. In conclusion, L. pneumophila OMVs are initially potent pro-inflammatory stimulators of macrophages, acting via TLR2, IRAK-1, and NF-κB, while at later time points, OMVs facilitate L. pneumophila replication by miR-146a-dependent IRAK-1 suppression. OMVs might thereby promote spreading of L. pneumophila in the host. Author SummaryOf all intracellular pathogens, Legionella pneumophila show the highest genetic adaptation to the host. They are important human pathogens causing mainly pneumonia, but are also PLOS Pathogens |

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Acinetobacter baumannii Outer Membrane Vesicles Elicit a Potent Innate Immune Response via Membrane Proteins

Cited by 113 publications

References 34 publications

Acinetobacter baumannii: biology and drug resistance — role of carbapenemases

Acinetobacter baumannii: biology and drug resistance — role of carbapenemases

Pathogenic Acinetobacter: from the Cell Surface to Infinity and Beyond

Legionella pneumophila-derived outer membrane vesicles promote bacterial replication in macrophages

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