scholarly journals Bacterial Membrane Vesicles in Pneumonia: From Mediators of Virulence to Innovative Vaccine Candidates

2021 ◽  
Vol 22 (8) ◽  
pp. 3858
Author(s):  
Felix Behrens ◽  
Teresa C. Funk-Hilsdorf ◽  
Wolfgang M. Kuebler ◽  
Szandor Simmons
Keyword(s):  
Extracellular Vesicles ◽  
Inflammatory Responses ◽  
Significant Proportion ◽  
Treatment Strategies ◽  
Membrane Vesicles ◽  
Multidrug Resistant ◽  
Biochemical Properties ◽  
Outer Membrane Vesicles ◽  
Vaccine Candidates ◽  
Treatment Regimens

Pneumonia due to respiratory infection with most prominently bacteria, but also viruses, fungi, or parasites is the leading cause of death worldwide among all infectious disease in both adults and infants. The introduction of modern antibiotic treatment regimens and vaccine strategies has helped to lower the burden of bacterial pneumonia, yet due to the unavailability or refusal of vaccines and antimicrobials in parts of the global population, the rise of multidrug resistant pathogens, and high fatality rates even in patients treated with appropriate antibiotics pneumonia remains a global threat. As such, a better understanding of pathogen virulence on the one, and the development of innovative vaccine strategies on the other hand are once again in dire need in the perennial fight of men against microbes. Recent data show that the secretome of bacteria consists not only of soluble mediators of virulence but also to a significant proportion of extracellular vesicles—lipid bilayer-delimited particles that form integral mediators of intercellular communication. Extracellular vesicles are released from cells of all kinds of organisms, including both Gram-negative and Gram-positive bacteria in which case they are commonly termed outer membrane vesicles (OMVs) and membrane vesicles (MVs), respectively. (O)MVs can trigger inflammatory responses to specific pathogens including S. pneumonia, P. aeruginosa, and L. pneumophila and as such, mediate bacterial virulence in pneumonia by challenging the host respiratory epithelium and cellular and humoral immunity. In parallel, however, (O)MVs have recently emerged as auspicious vaccine candidates due to their natural antigenicity and favorable biochemical properties. First studies highlight the efficacy of such vaccines in animal models exposed to (O)MVs from B. pertussis, S. pneumoniae, A. baumannii, and K. pneumoniae. An advanced and balanced recognition of both the detrimental effects of (O)MVs and their immunogenic potential could pave the way to novel treatment strategies in pneumonia and effective preventive approaches.

scholarly journals The benefits of exporting: engineered extracellular vesicles as promising vaccine candidates against enteric fever

2021 ◽  
pp. IAI.00001-21
Author(s):  
Marcio L. Rodrigues
Keyword(s):  
Genetic Engineering ◽  
Infectious Diseases ◽  
Extracellular Vesicles ◽  
Enteric Fever ◽  
Vaccine Candidate ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Vaccine Candidates

The immunological potential of extracellular vesicles produced by Gram-negative bacteria, the so-called outer-membrane vesicles (OMVs), can be improved by genetic engineering resulting in vesicles containing multiple immunogens. The potential of this approach for the development of a vaccine candidate for enteric fever was recently demonstrated by Gasperini and colleagues. This commentary will discuss the use of OMVs to generate vaccines for enteric fever and the promise of this approach for prevention of other infectious diseases.

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

scholarly journals Technologies to address antimicrobial resistance

2018 ◽  
Vol 115 (51) ◽  
pp. 12887-12895 ◽  
Author(s):  
Stephen J. Baker ◽  
David J. Payne ◽  
Rino Rappuoli ◽  
Ennio De Gregorio
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Membrane Vesicles ◽  
Multidrug Resistant ◽  
Outer Membrane Vesicles ◽  
Resistant Bacteria ◽  
Multiple Stakeholders ◽  
Global Challenge ◽  
Life Threatening ◽  
Bacterial Outer Membrane

Bacterial infections have been traditionally controlled by antibiotics and vaccines, and these approaches have greatly improved health and longevity. However, multiple stakeholders are declaring that the lack of new interventions is putting our ability to prevent and treat bacterial infections at risk. Vaccine and antibiotic approaches still have the potential to address this threat. Innovative vaccine technologies, such as reverse vaccinology, novel adjuvants, and rationally designed bacterial outer membrane vesicles, together with progress in polysaccharide conjugation and antigen design, have the potential to boost the development of vaccines targeting several classes of multidrug-resistant bacteria. Furthermore, new approaches to deliver small-molecule antibacterials into bacteria, such as hijacking active uptake pathways and potentiator approaches, along with a focus on alternative modalities, such as targeting host factors, blocking bacterial virulence factors, monoclonal antibodies, and microbiome interventions, all have potential. Both vaccines and antibacterial approaches are needed to tackle the global challenge of antimicrobial resistance (AMR), and both areas have the underpinning science to address this need. However, a concerted research agenda and rethinking of the value society puts on interventions that save lives, by preventing or treating life-threatening bacterial infections, are needed to bring these ideas to fruition.

scholarly journals Yersinia Outer Membrane Vesicles as Potential Vaccine Candidates in Protecting against Plague

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1694
Author(s):  
Andrey A. Byvalov ◽  
Ilya V. Konyshev ◽  
Vladimir N. Uversky ◽  
Svetlana V. Dentovskaya ◽  
Andrey P. Anisimov
Keyword(s):  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Vaccine Candidates ◽  
Lethal Infection ◽  
Potential Vaccine ◽  
Bacterial Outer Membrane ◽  
Vaccine Prophylaxis ◽  
Low Incidence ◽  
Plague Vaccine

Despite the relatively low incidence of plague, its etiological agent, Yersinia pestis, is an exceptional epidemic danger due to the high infectivity and mortality of this infectious disease. Reports on the isolation of drug-resistant Y. pestis strains indicate the advisability of using asymmetric responses, such as phage therapy and vaccine prophylaxis in the fight against this problem. The current relatively effective live plague vaccine is not approved for use in most countries because of its ability to cause heavy local and system reactions and even a generalized infectious process in people with a repressed immune status or metabolic disorders, as well as lethal infection in some species of nonhuman primates. Therefore, developing alternative vaccines is of high priority and importance. However, until now, work on the development of plague vaccines has mainly focused on screening for the potential immunogens. Several investigators have identified the protective potency of bacterial outer membrane vesicles (OMVs) as a promising basis for bacterial vaccine candidates. This review is aimed at presenting these candidates of plague vaccine and the results of their analysis in animal models.

Heterologous Expression of 3-O-Deacylase in Acinetobacter baumannii Modulates the Endotoxicity of Lipopolysaccharide

2015 ◽  
Vol 25 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Farzad Badmasti ◽  
Fereshteh Shahcheraghi ◽  
Seyed Davar Siadat ◽  
Saeid Bouzari ◽  
Soheila Ajdary ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Lipid A ◽  
Recombinant Dna ◽  
Inflammatory Responses ◽  
Acyl Chain ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Negative Ion ◽  
Recombinant Dna Technology ◽  
Whole Cells

The lipopolysaccharide (LPS) of <i>Acinetobacter baumannii</i> is a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6). The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A provides the opportunity to develop a new therapeutic compound that could reduce detrimental inflammatory responses. The plasmid pMMB66EH-PagL obtained by recombinant DNA technology was electroporated into <i>A. baumannii</i> ATCC 19606. Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1.

scholarly journals Tools of Aggregatibacter actinomycetemcomitans to Evade the Host Response

2019 ◽  
Vol 8 (7) ◽  
pp. 1079 ◽  
Author(s):  
Jan Oscarsson ◽  
Rolf Claesson ◽  
Mark Lindholm ◽  
Carola Höglund Åberg ◽  
Anders Johansson
Keyword(s):  
Host Response ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Treatment Resistance ◽  
Membrane Vesicles ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Outer Membrane Vesicles ◽  
Oral Microbiome ◽  
Connective Tissues ◽  
Ecological Changes

Periodontitis is an infection-induced inflammatory disease that affects the tooth supporting tissues, i.e., bone and connective tissues. The initiation and progression of this disease depend on dysbiotic ecological changes in the oral microbiome, thereby affecting the severity of disease through multiple immune-inflammatory responses. Aggregatibacter actinomycetemcomitans is a facultative anaerobic Gram-negative bacterium associated with such cellular and molecular mechanisms associated with the pathogenesis of periodontitis. In the present review, we outline virulence mechanisms that help the bacterium to escape the host response. These properties include invasiveness, secretion of exotoxins, serum resistance, and release of outer membrane vesicles. Virulence properties of A. actinomycetemcomitans that can contribute to treatment resistance in the infected individuals and upon translocation to the circulation, also induce pathogenic mechanisms associated with several systemic diseases.

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