scholarly journals ROS-dependent innate immune mechanisms control Staphylococcus aureus MRSA virulence in the Drosophila larval model

2020 ◽  
Author(s):  
Elodie Ramond ◽  
Anne Jamet ◽  
Xiongqi Ding ◽  
Clémence Bouvier ◽  
Louison Lallemant ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Responses ◽  
Shigella Flexneri ◽  
Light Sheet ◽  
Innate Immune ◽  
Health Concern ◽  
Infection Model ◽  
Human Pathogens ◽  
Posterior Midgut

AbstractAntibiotics multi-resistant Staphylococcus aureus strains constitute a major public health concern worldwide and are responsible of both healthcare- and community-associated infections. Here we have established a robust and simple S. aureus oral infection model, using Drosophila melanogaster larva, which allowed to follow S. aureus fate at the whole organism level as well as the host immune responses. Fluorescence microscopy and Light sheet 3D imaging revealed bacterial clustering at the posterior midgut that displays neutral pH. Our study demonstrates that S. aureus infection triggers host H2O2 production through Duox enzyme, consequently empowering antimicrobial peptides production through Toll pathway activation. We also show that catalase-mediated quenching of H2O2 not only enhances S. aureus survival but also minimizes host antimicrobial response, hence reducing bacterial clearance in vivo. Finally, we confirm the versatility of this model by demonstrating the colonization and host stimulation capacities of two other bacterial pathogens: Salmonella Typhimurium and Shigella flexneri. Overall, the drosophila larva may constitute a general model to follow in vivo host innate immune responses triggered upon infection with human pathogens.

scholarly journals The Resistance to Host Antimicrobial Peptides in Infections Caused by Daptomycin-Resistant Staphylococcus aureus

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 96
Author(s):  
Md Saruar Bhuiyan ◽  
Jhih-Hang Jiang ◽  
Xenia Kostoulias ◽  
Ravali Theegala ◽  
Graham J. Lieschke ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Responses ◽  
Antimicrobial Peptides ◽  
Innate Immune ◽  
Cross Resistance ◽  
Infection Model ◽  
Innate Immune Responses ◽  
Persistent Infections ◽  
Zebrafish Infection

Daptomycin is an important antibiotic for the treatment of infections caused by Staphylococcus aureus. The emergence of daptomycin resistance in S. aureus is associated with treatment failure and persistent infections with poor clinical outcomes. Here, we investigated host innate immune responses against clinically derived, daptomycin-resistant (DAP-R) and -susceptible S. aureus paired isolates using a zebrafish infection model. We showed that the control of DAP-R S. aureus infections was attenuated in vivo due to cross-resistance to host cationic antimicrobial peptides. These data provide mechanistic understanding into persistent infections caused by DAP-R S. aureus and provide crucial insights into the adaptive evolution of this troublesome pathogen.

scholarly journals Recent Advances in the Use of Galleria mellonella Model to Study Immune Responses against Human Pathogens

2018 ◽  
Vol 4 (4) ◽  
pp. 128 ◽  
Author(s):  
Thais Pereira ◽  
Patrícia de Barros ◽  
Luciana Fugisaki ◽  
Rodnei Rossoni ◽  
Felipe Ribeiro ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Galleria Mellonella ◽  
Cellular Responses ◽  
Innate Immune ◽  
In Vivo Studies ◽  
Human Pathogens ◽  
Radical Production ◽  
Humoral Responses

The use of invertebrates for in vivo studies in microbiology is well established in the scientific community. Larvae of Galleria mellonella are a widely used model for studying pathogenesis, the efficacy of new antimicrobial compounds, and immune responses. The immune system of G. mellonella larvae is structurally and functionally similar to the innate immune response of mammals, which makes this model suitable for such studies. In this review, cellular responses (hemocytes activity: phagocytosis, nodulation, and encapsulation) and humoral responses (reactions or soluble molecules released in the hemolymph as antimicrobial peptides, melanization, clotting, free radical production, and primary immunization) are discussed, highlighting the use of G. mellonella as a model of immune response to different human pathogenic microorganisms.

scholarly journals Serine-Aspartate Repeat Protein D Increases Staphylococcus aureus Virulence and Survival in Blood

2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Fatemeh Askarian ◽  
Satoshi Uchiyama ◽  
J. Andrés Valderrama ◽  
Clement Ajayi ◽  
Johanna U. E. Sollid ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Infection Model ◽  
Bacterial Survival ◽  
Bacterial Killing ◽  
Content Type ◽  
Repeat Protein

ABSTRACT Staphylococcus aureus expresses a panel of cell wall-anchored adhesins, including proteins belonging to the microbial surface components recognizing adhesive matrix molecule (MSCRAMM) family, exemplified by the serine-aspartate repeat protein D (SdrD), which serve key roles in colonization and infection. Deletion of sdrD from S. aureus subsp. aureus strain NCTC8325-4 attenuated bacterial survival in human whole blood ex vivo, which was associated with increased killing by human neutrophils. Remarkably, SdrD was able to inhibit innate immune-mediated bacterial killing independently of other S. aureus proteins, since addition of recombinant SdrD protein and heterologous expression of SdrD in Lactococcus lactis promoted bacterial survival in human blood. SdrD contributes to bacterial virulence in vivo, since fewer S. aureus subsp. aureus NCTC8325-4 ΔsdrD bacteria than bacteria of the parent strain were recovered from blood and several organs using a murine intravenous infection model. Collectively, our findings reveal a new property of SdrD as an important key contributor to S. aureus survival and the ability to escape the innate immune system in blood.

scholarly journals Acinetobacter baumannii phenylacetic acid metabolism influences infection outcome through a direct effect on neutrophil chemotaxis

2016 ◽  
Vol 113 (34) ◽  
pp. 9599-9604 ◽  
Author(s):  
Md Saruar Bhuiyan ◽  
Felix Ellett ◽  
Gerald L. Murray ◽  
Xenia Kostoulias ◽  
Gustavo M. Cerqueira ◽  
...  
Keyword(s):  
Immune Responses ◽  
Acinetobacter Baumannii ◽  
Phenylacetic Acid ◽  
Effector Proteins ◽  
Innate Immune ◽  
Infection Model ◽  
Transgenic Zebrafish ◽  
Neutrophil Chemotaxis ◽  
Virulence Regulator

Innate cellular immune responses are a critical first-line defense against invading bacterial pathogens. Leukocyte migration from the bloodstream to a site of infection is mediated by chemotactic factors that are often host-derived. More recently, there has been a greater appreciation of the importance of bacterial factors driving neutrophil movement during infection. Here, we describe the development of a zebrafish infection model to study Acinetobacter baumannii pathogenesis. By using isogenic A. baumannii mutants lacking expression of virulence effector proteins, we demonstrated that bacterial drivers of disease severity are conserved between zebrafish and mammals. By using transgenic zebrafish with fluorescent phagocytes, we showed that a mutation of an established A. baumannii global virulence regulator led to marked changes in neutrophil behavior involving rapid neutrophil influx to a localized site of infection, followed by prolonged neutrophil dwelling. This neutrophilic response augmented bacterial clearance and was secondary to an impaired A. baumannii phenylacetic acid catabolism pathway, which led to accumulation of phenylacetate. Purified phenylacetate was confirmed to be a neutrophil chemoattractant. These data identify a previously unknown mechanism of bacterial-guided neutrophil chemotaxis in vivo, providing insight into the role of bacterial metabolism in host innate immune evasion. Furthermore, the work provides a potentially new therapeutic paradigm of targeting a bacterial metabolic pathway to augment host innate immune responses and attenuate disease.

scholarly journals Role of BrnQ1 and BrnQ2 in Branched-Chain Amino Acid Transport and Virulence in Staphylococcus aureus

2014 ◽  
Vol 83 (3) ◽  
pp. 1019-1029 ◽  
Author(s):  
Julienne C. Kaiser ◽  
Sameha Omer ◽  
Jessica R. Sheldon ◽  
Ian Welch ◽  
David E. Heinrichs
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Gene ◽  
Defined Medium ◽  
Infection Model ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Branched Chain Amino Acid ◽  
Branched Chain

The branched-chain amino acids (BCAAs; Ile, Leu, and Val) not only are important nutrients for the growth ofStaphylococcus aureusbut also are corepressors for CodY, which regulates virulence gene expression, implicating BCAAs as an important link between the metabolic state of the cell and virulence. BCAAs are either synthesized intracellularly or acquired from the environment.S. aureusencodes three putative BCAA transporters, designated BrnQ1, BrnQ2, and BrnQ3; their functions have not yet been formally tested. In this study, we mutated all threebrnQparalogs so as to characterize their substrate specificities and their roles in growthin vitroandin vivo. We demonstrated that in the community-associated, methicillin-resistantS. aureus(CA-MRSA) strain USA300, BrnQ1 is involved in uptake of all three BCAAs, BrnQ2 transports Ile, and BrnQ3 does not have a significant role in BCAA transport under the conditions tested. Of the three, only BrnQ1 is essential for USA300 to grow in a chemically defined medium that is limited for Leu or Val. Interestingly, we observed that abrnQ2mutant grew better than USA300 in media limited for Leu and Val, owing to the fact that this mutation leads to overexpression ofbrnQ1. In a murine infection model, thebrnQ1mutant was attenuated, but in contrast,brnQ2mutants had significantly increased virulence compared to that of USA300, a phenotype we suggest is at least partially linked to enhancedin vivoscavenging of Leu and Val through BrnQ1. These data uncover a hitherto-undiscovered connection between nutrient acquisition and virulence in CA-MRSA.

scholarly journals Occurrence of foamy macrophages during the innate response of zebrafish to trypanosome infections

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sem H Jacobs ◽  
Eva Dóró ◽  
Ffion R Hammond ◽  
Mai E Nguyen-Chi ◽  
Georges Lutfalla ◽  
...  
Keyword(s):  
Immune Response ◽  
Early Response ◽  
Innate Immune ◽  
Infection Model ◽  
Parasite Control ◽  
Innate Response ◽  
Larval Zebrafish ◽  
Inflammatory Profile ◽  
Foamy Macrophages

A tightly regulated innate immune response to trypanosome infections is critical to strike a balance between parasite control and inflammation-associated pathology. In this study, we make use of the recently established Trypanosoma carassii infection model in larval zebrafish to study the early response of macrophages and neutrophils to trypanosome infections in vivo. We consistently identified high- and low-infected individuals and were able to simultaneously characterize their differential innate response. Not only did macrophage and neutrophil number and distribution differ between the two groups, but also macrophage morphology and activation state. Exclusive to high-infected zebrafish, was the occurrence of foamy macrophages characterized by a strong pro-inflammatory profile and potentially associated with an exacerbated immune response as well as susceptibility to the infection. To our knowledge this is the first report of the occurrence of foamy macrophages during an extracellular trypanosome infection.

scholarly journals The Sp1-Responsive microRNA-15b Negatively Regulates Rhabdovirus-Triggered Innate Immune Responses in Lower Vertebrates by Targeting TBK1

2021 ◽  
Vol 11 ◽  
Author(s):  
Renjie Chang ◽  
Qing Chu ◽  
Weiwei Zheng ◽  
Lei Zhang ◽  
Tianjun Xu
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune ◽  
Infection Model ◽  
Regulation Mechanism ◽  
Type I ◽  
Innate Immune Responses ◽  
Positive Role ◽  
Siniperca Chuatsi ◽  
Antiviral Immune Response

As is known to all, the production of type I interferon (IFN) plays pivotal roles in host innate antiviral immunity, and its moderate production play a positive role in promoting the activation of host innate antiviral immune response. However, the virus will establish a persistent infection model by interfering with the production of IFN, thereby evading the organism inherent antiviral immune response. Therefore, it is of great necessity to research the underlying regulatory mechanisms of type I IFN appropriate production under viral invasion. In this study, we report that a Sp1–responsive miR-15b plays a negative role in siniperca chuatsi rhabdovirus (SCRV)-triggered antiviral response in teleost fish. We found that SCRV could dramatically upregulate miiuy croaker miR-15b expression. Enhanced miR-15b could negatively regulate SCRV-triggered antiviral genes and inflammatory cytokines production by targeting TANK-binding kinase 1 (TBK1), thereby accelerating viral replication. Importantly, we found that miR-15b feedback regulates antiviral innate immune response through NF-κB and IRF3 signaling pathways. These findings highlight that miR-15b plays a crucial role in regulating virus–host interactions, which outlines a new regulation mechanism of fish’s innate immune responses.

scholarly journals Sanguiin H-6 Fractionated from Cloudberry (Rubus chamaemorus) Seeds Can Prevent the Methicillin-Resistant Staphylococcus aureus Biofilm Development during Wound Infection

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1481
Author(s):  
John Jairo Aguilera-Correa ◽  
Sara Fernández-López ◽  
Iskra Dennisse Cuñas-Figueroa ◽  
Sandra Pérez-Rial ◽  
Hanna-Leena Alakomi ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Wound Infection ◽  
Preventive Measure ◽  
Surgical Site Infections ◽  
Infection Model ◽  
Growth Media ◽  
Methicillin Resistant ◽  
Biofilm Development

Staphylococcus aureus is the most common cause of surgical site infections and its treatment is challenging due to the emergence of multi-drug resistant strains such as methicillin-resistant S. aureus (MRSA). Natural berry-derived compounds have shown antimicrobial potential, e.g., ellagitannins such as sanguiin H-6 and lambertianin C, the main phenolic compounds in Rubus seeds, have shown antimicrobial activity. The aim of this study was to evaluate the effect of sanguiin H-6 and lambertianin C fractionated from cloudberry seeds, on the MRSA growth, and as treatment of a MRSA biofilm development in different growth media in vitro and in vivo by using a murine wound infection model where sanguiin H-6 and lambertianin C were used to prevent the MRSA infection. Sanguiin H-6 and lambertianin C inhibited the in vitro biofilm development and growth of MRSA. Furthermore, sanguiin H-6 showed significant anti-MRSA effect in the in vivo wound model. Our study shows the possible use of sanguiin H-6 as a preventive measure in surgical sites to avoid postoperative infections, whilst lambertianin C showed no anti-MRSA activity.

scholarly journals 204. Antagonistic Effect of Colistin on Vancomycin Activity Against Methicillin-Resistant Staphylococcus aureus in in vitro and in vivo Studies

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S120-S121
Author(s):  
Sungim Choi ◽  
Taeeun Kim ◽  
Seongman Bae ◽  
Eunmi Yang ◽  
Su-Jin Park ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Antagonistic Effect ◽  
In Vivo Studies ◽  
Infection Model ◽  
Methicillin Resistant ◽  
Checkerboard Assay ◽  
Mrsa Strains ◽  
Time Kill

Abstract Background There is a concern that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concomitant colistin administered against multidrug-resistant gram-negative pathogen. Methods We confirmed the molecular genotypes of MRSA blood isolates collected in a tertiary hospital in Seoul, South Korea, and selected representative strains from the community-associated MRSA strains (CA-MRSA, ST72-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA, ST5-SCCmec II). USA CA-MRSA (USA300, ST8-SCCmec IV) and MRSA standard strain (ATCC 43300, ST39-SCCmec II) were also used for comparison with representative. We identified changes of the vancomycin MIC in MRSA by colistin exposure in a checkerboard assay and performed a time-kill assay to evaluate the combined effect of vancomycin and colistin on MRSA. In addition, we administered vancomycin, colistin, and combination of two antibiotics, respectively, to a neutropenic murine thigh infection model to evaluate the in vivo antagonistic effect of colistin on vancomycin treatment. Results In the checkerboard assay, all 4 MRSA strains showed a tendency for the vancomycin MIC to increase along with increasing concentrations of colistin. However, the time-kill assay showed the antagonism of vancomycin and colistin only against ST5-MRSA, when vancomycin concentration was 2 times the vancomycin MIC (Figure 1). No antagonism was observed in other strains. In the murine thigh infection model of ST5-MRSA, vancomycin monotherapy showed a significant log CFU reduction compared with a combination of vancomycin and colistin at 24 hours, demonstrating the antagonistic effect of vancomycin and colistin combination (Figure 2). Conclusion This study showed that exposure of colistin to certain MRSA strains may reduce the susceptibility to vancomycin. Combination therapy with vancomycin and colistin for MDR pathogens infections might result in treatment failure for concurrent MRSA infection. Disclosures All authors: No reported disclosures.

scholarly journals In vivo Pharmacodynamic Evaluation of Omadacycline (PTK 0796) against Staphylococcus aureus (SA) in the Murine Thigh Infection Model

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S478-S479 ◽  
Author(s):  
Alexander J Lepak ◽  
Miao Zhao ◽  
Karen Marchillo ◽  
Jamie VanHecker ◽  
David R Andes
Keyword(s):  
Staphylococcus Aureus ◽  
Infection Model
Sign in / Sign up

Export Citation Format

Share Document