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

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.

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

10.1101/2020.10.02.323444 ◽

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.

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

Frontiers in Immunology ◽

10.3389/fimmu.2020.625828 ◽

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.

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High-Resolution Profiling of Innate Immune Responses by Porcine Dendritic Cell Subsets in vitro and in vivo

Frontiers in Immunology ◽

10.3389/fimmu.2020.01429 ◽

2020 ◽

Vol 11 ◽

Cited By ~ 1

Author(s):

Gaël Auray ◽

Stephanie C. Talker ◽

Irene Keller ◽

Sylvie Python ◽

Markus Gerber ◽

...

Keyword(s):

Dendritic Cell ◽

High Resolution ◽

Immune Responses ◽

Innate Immune ◽

Innate Immune Responses ◽

Dendritic Cell Subsets

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A switch from constitutive chemical defence to inducible innate immune responses in the invasive ladybird Harmonia axyridis

Biology Letters ◽

10.1098/rsbl.2013.0006 ◽

2013 ◽

Vol 9 (3) ◽

pp. 20130006 ◽

Cited By ~ 21

Author(s):

Henrike Schmidtberg ◽

Christian Röhrich ◽

Heiko Vogel ◽

Andreas Vilcinskas

Keyword(s):

Immune Responses ◽

Antimicrobial Peptides ◽

Harmonia Axyridis ◽

Chemical Defence ◽

Coccinella Septempunctata ◽

Invasion Biology ◽

Innate Immune ◽

Innate Immune Responses ◽

Simultaneous Synthesis ◽

Related Proteins

The harlequin ladybird, Harmonia axyridis , has emerged as a model species for invasion biology, reflecting its remarkable capacity to outcompete native ladybird species when introduced into new habitats. This ability may be associated with its prominent resistance to pathogens and intraguild predation. We recently showed that the constitutive antibacterial activity present in the haemolymph of H. axyridis beetles can be attributed to the chemical defence compound harmonine. Here, we demonstrate that H. axyridis differs from other insects, including the native ladybird Coccinella septempunctata, by reducing rather than increasing the antimicrobial activity of its haemolymph following the injection of bacteria. However, both species produce new or more abundant proteins in the haemolymph, indicating that bacterial challenge induces innate immune responses associated with the synthesis of immunity-related proteins. Our results suggest that H. axyridis beetles can switch from constitutive chemical defence to inducible innate immune responses, supporting hypothesis that inducible antimicrobial peptides protect host beetles against pathogens that survive constitutive defences. These alternative antimicrobial defence mechanisms may reflect a trade-off resulting from fitness-related costs associated with the simultaneous synthesis of harmonine and antimicrobial peptides/proteins.

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