Host–pathogen interactions in Acinetobacter baumannii infection: recent advances and future challenges

Abstract Since the discovery of mimivirus, numerous giant viruses associated with free-living amoebae have been described. The genome of giant viruses can be more than 2.5 megabases, and virus particles can exceed the size of many bacteria. The unexpected characteristics of these viruses have made them intriguing research targets and, as a result, studies focusing on their interactions with their amoeba host have gained increased attention. Studies have shown that giant viruses can establish host–pathogen interactions, which have not been previously demonstrated, including the unprecedented interaction with a new group of small viruses, called virophages, that parasitize their viral factories. In this brief review, we present recent advances in virophage–giant virus–host interactions and highlight selected studies involving interactions between giant viruses and amoebae. These unprecedented interactions involve the giant viruses mimivirus, marseillevirus, tupanviruses and faustovirus, all of which modulate the amoeba environment, affecting both their replication and their spread to new hosts.

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Quantitative proteomic analysis of host—pathogen interactions: a study of Acinetobacter baumannii responses to host airways

BMC Genomics ◽

10.1186/s12864-015-1608-z ◽

2015 ◽

Vol 16 (1) ◽

Cited By ~ 20

Author(s):

Jose Antonio Méndez ◽

Jesús Mateos ◽

Alejandro Beceiro ◽

María Lopez ◽

María Tomás ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Proteomic Analysis ◽

Host Pathogen Interactions ◽

Quantitative Proteomic Analysis ◽

Host Pathogen

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Gene expression profiling in human neutrophils after infection with Acinetobacter baumannii in vitro

PLoS ONE ◽

10.1371/journal.pone.0242674 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0242674

Author(s):

María Lázaro-Díez ◽

Itziar Chapartegui-González ◽

Borja Suberbiola ◽

J. Gonzalo Ocejo-Vinyals ◽

Marcos López-Hoyos ◽

...

Keyword(s):

Gene Expression ◽

Acinetobacter Baumannii ◽

Protein Quantification ◽

Effector Proteins ◽

Human Neutrophils ◽

Host Pathogen Interactions ◽

Proinflammatory Response ◽

Host Pathogen ◽

Key Aspects

Acinetobacter baumannii is a Gram negative nosocomial pathogen that has acquired increasing worldwide notoriety due to its high antibiotic resistance range and mortality rates in hospitalized patients. Therefore, it is necessary to better understand key aspects of A. baumannii pathogenesis such as host-pathogen interactions. In this report, we analyzed both gene expression and cytokine production by human neutrophils infected with A. baumannii. Our assays reveal a proinflammatory response of neutrophils after A. baumannii infection, since intracellular transcription of effector proteins such as COX-2, transcription factors, and proinflammatory cytokines resulted significantly upregulated in neutrophils infected by A. baumannii, compared with unstimulated human neutrophils. Translation and release of CXCL-8, IL-1β and TNF-α by neutrophils was confirmed by protein quantification in culture supernatants. Results obtained in this report reinforce the importance of human neutrophils in controlling A. baumannii infections but also emphasize the proinflammatory nature of these host-pathogen interactions as a target for future immunomodulatory therapies.

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An Update on Host-Pathogen Interplay and Modulation of Immune Responses duringOrientia tsutsugamushiInfection

Clinical Microbiology Reviews ◽

10.1128/cmr.00076-17 ◽

2018 ◽

Vol 31 (2) ◽

Cited By ~ 12

Author(s):

Fabián E. Díaz ◽

Katia Abarca ◽

Alexis M. Kalergis

Keyword(s):

Animal Models ◽

Immune Responses ◽

Model Development ◽

Scientific Progress ◽

Organ Injury ◽

Effective Vaccine ◽

Host Pathogen Interactions ◽

Content Type ◽

Recent Advances ◽

Host Pathogen

SUMMARYThe obligate intracellular bacteriumOrientia tsutsugamushiis the causative agent of scrub typhus in humans, a serious mite-borne disease present in a widespread area of endemicity, which affects an estimated 1 million people every year. This disease may exhibit a broad range of presentations, ranging from asymptomatic to fatal conditions, with the latter being due to disseminated endothelial infection and organ injury. Unique characteristics of the biology and host-pathogen interactions ofO. tsutsugamushi, including the high antigenic diversity among strains and the highly variable, short-lived memory responses developed by the host, underlie difficulties faced in the pursuit of an effective vaccine, which is an imperative need. Other factors that have hindered scientific progress relative to the infectious mechanisms of and the immune response triggered by this bacterium in vertebrate hosts include the limited number of mechanistic studies performed on animal models and the lack of genetic tools currently available for this pathogen. However, recent advances in animal model development are promising to improve our understanding of host-pathogen interactions. Here, we comprehensively discuss the recent advances in and future perspectives on host-pathogen interactions and the modulation of immune responses related to this reemerging disease, highlighting the role of animal models.

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Acinetobacter baumannii: An Ancient Commensal with Weapons of a Pathogen

Pathogens ◽

10.3390/pathogens10040387 ◽

2021 ◽

Vol 10 (4) ◽

pp. 387

Author(s):

Meysam Sarshar ◽

Payam Behzadi ◽

Daniela Scribano ◽

Anna Teresa Palamara ◽

Cecilia Ambrosi

Keyword(s):

Acinetobacter Baumannii ◽

Virulence Factors ◽

Current Data ◽

Comparative Genomic ◽

Host Immune System ◽

Host Pathogen Interactions ◽

In Vivo Models ◽

Host Pathogen

Acinetobacter baumannii is regarded as a life-threatening pathogen associated with community-acquired and nosocomial infections, mainly pneumonia. The rise in the number of A. baumannii antibiotic-resistant strains reduces effective therapies and increases mortality. Bacterial comparative genomic studies have unraveled the innate and acquired virulence factors of A. baumannii. These virulence factors are involved in antibiotic resistance, environmental persistence, host-pathogen interactions, and immune evasion. Studies on host–pathogen interactions revealed that A. baumannii evolved different mechanisms to adhere to in order to invade host respiratory cells as well as evade the host immune system. In this review, we discuss current data on A. baumannii genetic features and virulence factors. An emphasis is given to the players in host–pathogen interaction in the respiratory tract. In addition, we report recent investigations into host defense systems using in vitro and in vivo models, providing new insights into the innate immune response to A. baumannii infections. Increasing our knowledge of A. baumannii pathogenesis may help the development of novel therapeutic strategies based on anti-adhesive, anti-virulence, and anti-cell to cell signaling pathways drugs.

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Galleria mellonella as a Model System To Study Acinetobacter baumannii Pathogenesis and Therapeutics

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01533-08 ◽

2009 ◽

Vol 53 (6) ◽

pp. 2605-2609 ◽

Cited By ~ 187

Author(s):

Anton Y. Peleg ◽

Sebastian Jara ◽

Divya Monga ◽

George M. Eliopoulos ◽

Robert C. Moellering ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Galleria Mellonella ◽

Incubation Temperature ◽

Model System ◽

Model Systems ◽

Infection Model ◽

Acinetobacter Baylyi ◽

Host Pathogen Interactions ◽

Host Pathogen

ABSTRACT Nonmammalian model systems of infection such as Galleria mellonella (caterpillars of the greater wax moth) have significant logistical and ethical advantages over mammalian models. In this study, we utilize G. mellonella caterpillars to study host-pathogen interactions with the gram-negative organism Acinetobacter baumannii and determine the utility of this infection model to study antibacterial efficacy. After infecting G. mellonella caterpillars with a reference A. baumannii strain, we observed that the rate of G. mellonella killing was dependent on the infection inoculum and the incubation temperature postinfection, with greater killing at 37°C than at 30°C (P = 0.01). A. baumannii strains caused greater killing than the less-pathogenic species Acinetobacter baylyi and Acinetobacter lwoffii (P < 0.001). Community-acquired A. baumannii caused greater killing than a reference hospital-acquired strain (P < 0.01). Reduced levels of production of the quorum-sensing molecule 3-hydroxy-C12-homoserine lactone caused no change in A. baumannii virulence against G. mellonella. Treatment of a lethal A. baumannii infection with antibiotics that had in vitro activity against the infecting A. baumannii strain significantly prolonged the survival of G. mellonella caterpillars compared with treatment with antibiotics to which the bacteria were resistant. G. mellonella is a relatively simple, nonmammalian model system that can be used to facilitate the in vivo study of host-pathogen interactions in A. baumannii and the efficacy of antibacterial agents.

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Molecular and cellular pathobiology ofEhrlichiainfection: targets for new therapeutics and immunomodulation strategies

Expert Reviews in Molecular Medicine ◽

10.1017/s1462399410001730 ◽

2011 ◽

Vol 13 ◽

Cited By ~ 35

Author(s):

Jere W. McBride ◽

David H. Walker

Keyword(s):

New Technologies ◽

Vaccine Development ◽

Severe Disease ◽

Acute Infection ◽

Effector Proteins ◽

Host Pathogen Interactions ◽

Disease States ◽

Recent Advances ◽

Host Pathogen ◽

Life Threatening

Ehrlichiaare small obligately intracellular bacteria in the order Rickettsiales that are transmitted by ticks and associated with emerging life-threatening human zoonoses. Vaccines are not available for human ehrlichiosis, and therapeutic options are limited to a single antibiotic class. New technologies for exploring host–pathogen interactions have yielded recent advances in understanding the molecular interactions betweenEhrlichiaand the eukaryotic host cell and identified new targets for therapeutic and vaccine development, including those that target pathogen virulence mechanisms or disrupt the processes associated with ehrlichial effector proteins. Animal models have also provided insight into immunopathological mechanisms that contribute significantly to understanding severe disease manifestations, which should lead to the development of immunomodulatory approaches for treating patients nearing or experiencing severe disease states. In this review, we discuss the recent advances in our understanding of molecular and cellular pathobiology and the immunobiology ofEhrlichiainfection. We identify new molecular host–pathogen interactions that can be targets of new therapeutics, and discuss prospects for treating the immunological dysregulation during acute infection that leads to life-threatening complications.

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