Retraction Note: IspH inhibitors kill Gram-negative bacteria and mobilize immune clearance

Singh, Kumar Sachin; Sharma, Rolee; Reddy, Poli Adi Narayana; Vonteddu, Prashanthi; Good, Madeline; Sundarrajan, Anjana; Choi, Hyeree; Muthumani, Kar; Kossenkov, Andrew V.; Goldman, Aaron R.; Tang, Hsin‐Yao; Totrov, Maxim; Cassel, Joel; Murphy, Maureen E.; Somasundaram, Rajasekharan; Herlyn, Meenhard; Salvino, Joseph M.; Dotiwala, Farokh

doi:10.1038/s41586-021-03961-x

Cited by 7 publications

(15 citation statements)

References 48 publications

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“…2f). 7 All the above results suggest that HMMP is capable of disrupting the integrity of bacteria and consequently promote the outward release of bacterial antigens. In the meantime, we analyzed the intrabacterial ROS generation performance to disclose the underlying antibacterial mechanism induced by HMMP.…”

Section: Hmmp-potentiated In Situ Burst Bacterial Antigen Releasementioning

confidence: 89%

“…Uncontrolled local bacterial infections can progressively develop into fatal status characteristic of bacteremia and distant organ injuries. 6,7 Besides, infection-associated immunosuppression would predispose the host to secondary infections 41 . To assess whether the in situ nanovaccination could induce potent systemic antibacterial immune responses which would prevent the formation of distant infection foci, we constructed a contralateral osteomyelitis model after the immunization by HMMP administration (Fig.…”

Section: Hmmp-in Amed Transferable Antibacterial Immune Responsesmentioning

confidence: 99%

“…4,5 However, a crucial drawback of these methods is the limited depth of light penetration, making them impotent in eliminating deep bone infections. 6 The emergence and circulation of multidrug-resistant strains, such as Staphylococcus aureus (S. aureus) and Mycobacterium tuberculosis (M. tuberculosis), are largely attributed to their capability to mount effective anti-immune responses 7,8 . Invading pathogens could inhibit antigen presentations by camou aging their antigen epitopes to escape from immune surveillance, reprogramming macrophages to an M2 phenotype and/or even killing antigen-presenting cells.…”

Section: Introductionmentioning

confidence: 99%

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Biomimetic Nanomedicine-Triggered in Situ Vaccination for Innate and Adaptive Immunity Activations for Bacterial Osteomyelitis Treatment

et al. 2022

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The development of bacterial vaccines for inducing immunoresponse against infectious diseases such as osteomyelitis is of great signi cance and importance. However, the responsiveness of bacterial immunotherapy remains far from being satisfactory largely due to the erratic antigen epitopes of bacteria. Herein, we report an in situ vaccination strategy for the immunotherapy of bacterial infection based on an osteomyelitis model using a biomimetic nanomedicine named as HMMP, which was constructed by engineering PpIX-encapsulated hollow MnO x with a hybrid membrane exfoliated from both macrophage and tumor cell lines. The as-established HMMP features a burst bacterial antigen release as the in situ vaccine by the augmented sonodynamic treatment, and the resultant priming of antigen presenting cells for the following activations of both cellular and humoral adaptive immunities against bacterial infections. This treatment regimen not only triggers initial bacterial regression in established osteomyelitis model, also simultaneously generate robust systemic antibacterial immunity against poorly immunogenic secondary osteomyelitis in the contralateral knee as well, and additionally, confers long-lasting bacteria-speci c immune memory responses to prevent infection relapse. Thus, our study provides a proof of concept of in situ vaccination for the activation of both innate and adaptive antibacterial immune responses, providing an individual-independent bacterial immunotherapy.

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Section: Hmmp-potentiated In Situ Burst Bacterial Antigen Releasementioning

confidence: 89%

Section: Hmmp-in Amed Transferable Antibacterial Immune Responsesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biomimetic Nanomedicine-Triggered in Situ Vaccination for Innate and Adaptive Immunity Activations for Bacterial Osteomyelitis Treatment

et al. 2022

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“…In recent years, new classes of antimicrobials known as dual-acting immuno-antibiotics (DAIAs) were introduced that target the non-mevalonate or methyl-D-erythritol phosphate (MEP) pathway of isoprenoid biosynthesis and riboflavin biosynthesis pathway in bacteria (Figure 1). 41,42 They showed a twopronged approach to developing new molecules that can kill MDR microorganisms while also boosting the natural immune response of the host. These new DAIAs, which combine the direct killing capabilities of antibiotics with the inherent capability of the immune system to generate synergy, is regarded to be a potential watershed point in the global fight against AMR.…”

Section: Antibiotics Have Been Shown To Target Vital Bacterial Activi...mentioning

confidence: 99%

“…The researchers focused on the MEP metabolic pathway, which is required by almost all bacteria but not found in humans, thereby making it an attractive target for designing antibiotics. [41][42][43] Singh et al concentrated on the MEP, also known as the non-mevalonate pathway, which is involved in the synthesis of isoprenoids, an essential molecule required by most pathogenic bacteria for survival. 41 The true target was the killing of bacteria by the inhibition of the IspH enzyme required for isoprenoid biosynthesis.…”

Section: Antibiotics Have Been Shown To Target Vital Bacterial Activi...mentioning

confidence: 99%

Antibiotic resistance: The challenges and some emerging strategies for tackling a global menace

Nwobodo

Ugwu

Anie

et al. 2022

Clinical Laboratory Analysis

254

104

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Background Antibiotic resistance is currently the most serious global threat to the effective treatment of bacterial infections. Antibiotic resistance has been established to adversely affect both clinical and therapeutic outcomes, with consequences ranging from treatment failures and the need for expensive and safer alternative drugs to the cost of higher rates of morbidity and mortality, longer hospitalization, and high‐healthcare costs. The search for new antibiotics and other antimicrobials continues to be a pressing need in humanity's battle against bacterial infections. Antibiotic resistance appears inevitable, and there is a continuous lack of interest in investing in new antibiotic research by pharmaceutical industries. This review summarized some new strategies for tackling antibiotic resistance in bacteria. Methods To provide an overview of the recent research, we look at some new strategies for preventing resistance and/or reviving bacteria's susceptibility to already existing antibiotics. Results Substantial pieces of evidence suggest that antimicrobials interact with host immunity, leading to potent indirect effects that improve antibacterial activities and may result in more swift and complete bactericidal effects. A new class of antibiotics referred to as immuno‐antibiotics and the targeting of some biochemical resistance pathway components including inhibition of SOS response and hydrogen sulfide as biochemical underlying networks of bacteria can be considered as new emerging strategies to combat antibiotic resistance in bacteria. Conclusion This review highlighted and discussed immuno‐antibiotics and inhibition of SOS response and hydrogen sulfide as biochemical underlying networks of bacteria as new weapons against antibiotic resistance in bacteria.

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Arginine‐Enhanced Antimicrobial Activity of Nanozymes against Gram‐Negative Bacteria

Zhao,

Wen,

Song

et al. 2023

Adv Healthcare Materials

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The continuous reduction of clinically available antibiotics has made it imperative to exploit more effective antimicrobial therapies, especially for difficult‐to‐treat Gram‐negative pathogens. Herein, we showed that the combination of an antimicrobial nanozyme with the clinically compatible basic amino acid L‐arginine affords a potent treatment for infections with Gram‐negative pathogens. In particular, the antimicrobial activity of the antimicrobial nanozyme was dramatically increased by approximately 1000‐fold after L‐arginine stimulation. Specifically, the combination therapy enhanced bacterial outer and inner membrane permeability and promoted intracellular reactive oxygen species (ROS) generation. Moreover, the metabolomic and transcriptomic results revealed that combination treatment led to the increased ROS‐mediated damage by inhibiting the tricarboxylic acid cycle and oxidative phosphorylation, thereby inducing an imbalance of the antioxidant and oxidant systems. Importantly, L‐arginine dramatically significantly accelerated the healing of infected wounds in mouse models of multidrug‐resistant peritonitis‐sepsis and skin wound infection. Overall, this work demonstrates a novel synergistic antibacterial strategy by combining the antimicrobial nanozymes with L‐arginine, which substantively facilitates the nanozyme‐mediated killing of pathogens by promoting ROS production.This article is protected by copyright. All rights reserved

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Retraction Note: IspH inhibitors kill Gram-negative bacteria and mobilize immune clearance

Cited by 7 publications

References 48 publications

Biomimetic Nanomedicine-Triggered in Situ Vaccination for Innate and Adaptive Immunity Activations for Bacterial Osteomyelitis Treatment

Biomimetic Nanomedicine-Triggered in Situ Vaccination for Innate and Adaptive Immunity Activations for Bacterial Osteomyelitis Treatment

Antibiotic resistance: The challenges and some emerging strategies for tackling a global menace

Arginine‐Enhanced Antimicrobial Activity of Nanozymes against Gram‐Negative Bacteria

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