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

2009 ◽  
Vol 53 (6) ◽  
pp. 2605-2609 ◽  
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.

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

PLoS ONE ◽  
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.

scholarly journals The antimicrobial activity of silver acetate against Acinetobacter baumannii in a Galleria mellonella infection model

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11196
Author(s):  
Eden Mannix-Fisher ◽  
Samantha McLean
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Galleria Mellonella ◽  
World Health Organisation ◽  
World Health ◽  
Infection Model ◽  
Silver Acetate ◽  
Selective Toxicity ◽  
Carbapenem Resistant

Background The increasing prevalence of bacterial infections that are resistant to antibiotic treatment has caused the scientific and medical communities to look for alternate remedies aimed at prevention and treatment. In addition to researching novel antimicrobials, there has also been much interest in revisiting some of the earliest therapies used by man. One such antimicrobial is silver; its use stretches back to the ancient Greeks but interest in its medicinal properties has increased in recent years due to the rise in antibiotic resistance. Currently antimicrobial silver is found in everything from lunch boxes to medical device implants. Though much is claimed about the antimicrobial efficacy of silver salts the research in this area is mixed. Methods Herein we investigated the efficacy of silver acetate against a carbapenem resistant strain of Acinetobacter baumannii to determine the in vitro activity of this silver salt against a World Health Organisation designated category I critical pathogen. Furthermore, we use the Galleria mellonella larvae model to assess toxicity of the compound and its efficacy in treating infections in a live host. Results We found that silver acetate can be delivered safely to Galleria at medically relevant and antimicrobial levels without detriment to the larvae and that administration of silver acetate to an infection model significantly improved survival. This demonstrates the selective toxicity of silver acetate for bacterial pathogens but also highlights the need for administration of well-defined doses of the antimicrobial to provide an efficacious treatment.

scholarly journals Phenotypic switching in Candida tropicalis alters host-pathogen interactions in a Galleria mellonella infection model

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hugo F. Perini ◽  
Alane T. P. Moralez ◽  
Ricardo S. C. Almeida ◽  
Luciano A. Panagio ◽  
Admilton O. G. Junior ◽  
...  
Keyword(s):  
Candida Tropicalis ◽  
Galleria Mellonella ◽  
Phenotypic Switching ◽  
Infection Model ◽  
Host Pathogen Interactions ◽  
Host Pathogen

scholarly journals Construction and Application of aluxABCDEReporter System for Real-Time Monitoring of Enterococcus faecalis Gene Expression and Growth

2012 ◽  
Vol 78 (19) ◽  
pp. 7003-7011 ◽  
Author(s):  
Sabina Leanti La Rosa ◽  
Dzung B. Diep ◽  
Ingolf F. Nes ◽  
Dag Anders Brede
Keyword(s):  
Real Time ◽  
Enterococcus Faecalis ◽  
Galleria Mellonella ◽  
Viable Cell ◽  
Model Systems ◽  
Infection Model ◽  
Broad Host Range ◽  
Reporter System ◽  
Content Type

ABSTRACTThe present work describes the construction of a novel molecular tool for luciferase-based bioluminescence (BL) tagging ofEnterococcus faecalis. To this end, a vector (pSL101) and its derivatives conferring a genetically encoded bioluminescent phenotype on all tested strains ofE. faecaliswere constructed. pSL101 harbors theluxABCDEoperon from pPL2luxand the pREG696 broad-host-range replicon andaxe-txetoxin-antitoxin cassette, providing segregational stability for long-term plasmid persistence in the absence of antibiotic selection. The bioluminescent signals obtained from three highly expressed promoters correlated linearly (R2> 0.98) with the viable-cell count. We employedlux-taggedE. faecalisstrains to monitor growth in real time in milk and urinein vitro. Furthermore, bioluminescence imaging (BLI) was used to visualize the magnitude of the bacterial burden during infection in theGalleria mellonellamodel system. To our knowledge, pSL101 is the first substrate addition-independent reporter system developed for BLI ofE. faecalisand an efficient tool for spatiotemporal tracking of bacterial growth and quantitative determination of promoter activity in real time, noninvasively, in infection model systems.

scholarly journals Acinetobacter baumannii: An Ancient Commensal with Weapons of a Pathogen

Pathogens ◽  
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.

scholarly journals A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jaeeun Park ◽  
Misung Kim ◽  
Bora Shin ◽  
Mingyeong Kang ◽  
Jihye Yang ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Outer Membrane ◽  
Galleria Mellonella ◽  
Membrane Vesicles ◽  
Polymyxin B ◽  
Outer Membrane Vesicles ◽  
Clinical Isolates ◽  
Infection Model ◽  
Taxonomic Profiling

Modification of the outer membrane charge by a polymyxin B (PMB)-induced PmrAB two-component system appears to be a dominant phenomenon in PMB-resistant Acinetobacter baumannii. PMB-resistant variants and many clinical isolates also appeared to produce outer membrane vesicles (OMVs). Genomic, transcriptomic, and proteomic analyses revealed that upregulation of the pmr operon and decreased membrane-linkage proteins (OmpA, OmpW and BamE) are linked to overproduction of OMVs, which also promoted enhanced biofilm formation. The addition of OMVs from PMB-resistant variants into the cultures of PMB-susceptible A. baumannii and the clinical isolates protected these susceptible bacteria from PMB. Taxonomic profiling of in vitro human gut microbiomes under anaerobic conditions demonstrated that OMVs completely protected the microbial community against PMB treatment. A Galleria mellonella-infection model with PMB treatment showed that OMVs increased the mortality rate of larvae by protecting A. baumannii from PMB. Taken together, OMVs released from A. baumannii functioned as decoys against PMB.

scholarly journals Characterization of the Differential Pathogenicity of Candida auris in a Galleria mellonella Infection Model

2021 ◽  
Author(s):  
Victor Garcia-Bustos ◽  
Amparo Ruiz-Saurí ◽  
Alba Ruiz-Gaitán ◽  
Ignacio Antonio Sigona-Giangreco ◽  
Marta Dafne Cabañero-Navalon ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Galleria Mellonella ◽  
Infection Model ◽  
Host Pathogen Interactions ◽  
Candida Auris ◽  
Content Type ◽  
Host Pathogen ◽  
Global Threat

Candida auris is an emergent fungus that has become a global threat due to its multidrug resistance, mortality, and transmissibility. These unique features make it different from other Candida species, but we still do not fully know the degree of virulence and, especially, the host-pathogen interactions.

Antisense inhibition of lpxB gene expression in Acinetobacter baumannii by peptide–PNA conjugates and synergy with colistin

2019 ◽  
Vol 75 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Marta Martínez-Guitián ◽  
Juan Carlos Vázquez-Ucha ◽  
Laura Álvarez-Fraga ◽  
Kelly Conde-Pérez ◽  
Germán Bou ◽  
...  
Keyword(s):  
Survival Rate ◽  
Acinetobacter Baumannii ◽  
Lipid A ◽  
Galleria Mellonella ◽  
A549 Cells ◽  
Infection Model ◽  
Kill Curve ◽  
Time Kill

Abstract Background LpxB is an enzyme involved in the biosynthesis pathway of lipid A, a component of LPS. Objectives To evaluate the lpxB gene in Acinetobacter baumannii as a potential therapeutic target and to propose antisense agents such as peptide nucleic acids (PNAs) as a tool to combat bacterial infection, either alone or in combination with known antimicrobial therapies. Methods RNA-seq analysis of the A. baumannii ATCC 17978 strain in a murine pneumonia model was performed to study the in vivo expression of lpxB. Protein expression was studied in the presence or absence of anti-lpxB (KFF)3K-PNA (pPNA). Time–kill curve analyses and protection assays of infected A549 cells were performed. The chequerboard technique was used to test for synergy between pPNA and colistin. A Galleria mellonella infection model was used to test the in vivo efficacy of pPNA. Results The lpxB gene was overexpressed during pneumonia. Treatment with a specific pPNA inhibited LpxB expression in vitro, decreased survival of the ATCC 17978 strain and increased the survival rate of infected A549 cells. Synergy was observed between pPNA and colistin in colistin-susceptible strains. In vivo assays confirmed that a combination treatment of anti-lpxB pPNA and colistin was more effective than colistin in monotherapy. Conclusions The lpxB gene is essential for A. baumannii survival. Anti-lpxB pPNA inhibits LpxB expression, causing bacterial death. This pPNA showed synergy with colistin and increased the survival rate in G. mellonella. The data suggest that antisense pPNA molecules blocking the lpxB gene could be used as antibacterial agents.

scholarly journals Designing P. aeruginosa synthetic phages with reduced genomes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Diana P. Pires ◽  
Rodrigo Monteiro ◽  
Dalila Mil-Homens ◽  
Arsénio Fialho ◽  
Timothy K. Lu ◽  
...  
Keyword(s):  
Galleria Mellonella ◽  
Antibacterial Properties ◽  
Genetically Engineered ◽  
In Vivo Studies ◽  
Infection Model ◽  
Promising Therapeutic Approach ◽  
Genes Encoding ◽  
First Time

AbstractIn the era where antibiotic resistance is considered one of the major worldwide concerns, bacteriophages have emerged as a promising therapeutic approach to deal with this problem. Genetically engineered bacteriophages can enable enhanced anti-bacterial functionalities, but require cloning additional genes into the phage genomes, which might be challenging due to the DNA encapsulation capacity of a phage. To tackle this issue, we designed and assembled for the first time synthetic phages with smaller genomes by knocking out up to 48% of the genes encoding hypothetical proteins from the genome of the newly isolated Pseudomonas aeruginosa phage vB_PaeP_PE3. The antibacterial efficacy of the wild-type and the synthetic phages was assessed in vitro as well as in vivo using a Galleria mellonella infection model. Overall, both in vitro and in vivo studies revealed that the knock-outs made in phage genome do not impair the antibacterial properties of the synthetic phages, indicating that this could be a good strategy to clear space from phage genomes in order to enable the introduction of other genes of interest that can potentiate the future treatment of P. aeruginosa infections.

scholarly journals Cerebrospinal fluid (CSF) augments metabolism and virulence expression factors in Acinetobacter baumannii

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jasmine Martinez ◽  
Chelsea Razo-Gutierrez ◽  
Casin Le ◽  
Robert Courville ◽  
Camila Pimentel ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
Atp Synthesis ◽  
Bloodstream Infections ◽  
Model Systems ◽  
Phenotypic Traits ◽  
Virulence Determinants ◽  
Expression Of Genes

AbstractIn a recent report by the Centers for Disease Control and Prevention (CDC), multidrug resistant (MDR) Acinetobacter baumannii is a pathogen described as an “urgent threat.” Infection with this bacterium manifests as different diseases such as community and nosocomial pneumonia, bloodstream infections, endocarditis, infections of the urinary tract, wound infections, burn infections, skin and soft tissue infections, and meningitis. In particular, nosocomial meningitis, an unwelcome complication of neurosurgery caused by extensively-drug resistant (XDR) A. baumannii, is extremely challenging to manage. Therefore, understanding how A. baumannii adapts to different host environments, such as cerebrospinal fluid (CSF) that may trigger changes in expression of virulence factors that are associated with the successful establishment and progress of this infection is necessary. The present in-vitro work describes, the genetic changes that occur during A. baumannii infiltration into CSF and displays A. baumannii’s expansive versatility to persist in a nutrient limited environment while enhancing several virulence factors to survive and persist. While a hypervirulent A. baumannii strain did not show changes in its transcriptome when incubated in the presence of CSF, a low-virulence isolate showed significant differences in gene expression and phenotypic traits. Exposure to 4% CSF caused increased expression of virulence factors such as fimbriae, pilins, and iron chelators, and other virulence determinants that was confirmed in various model systems. Furthermore, although CSF's presence did not enhance bacterial growth, an increase of expression of genes encoding transcription, translation, and the ATP synthesis machinery was observed. This work also explores A. baumannii’s response to an essential component, human serum albumin (HSA), within CSF to trigger the differential expression of genes associated with its pathoadaptibility in this environment.

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