Impact of IMT-P8 on the Efficacy of Conventional Antibiotics for the Treatment of Drug-Resistant and Intracellular Staphylococcus aureus.

IF 3.8 2区医学 Q2 CHEMISTRY, MEDICINAL

ACS Infectious Diseases Pub Date : 2025-07-05 DOI:10.1021/acsinfecdis.5c00278

Vidhu Singh, Sharmila Talukdar, Niharika Nirwal, Manoj Raje, Prabhat Ranjan Mishra, Hemraj Nandanwar

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Abstract

Addressing the issue of antimicrobial resistance is of the utmost importance on a global scale. We are in dire need of innovative methods and alternatives to new antibiotic discovery in order to address the growing problem of antimicrobial resistance. In this study, we investigated the efficacy of cell-penetrating peptide (IMT-P8) as an adjuvant to enhance the activity of conventional antibiotics against multidrug-resistant and intracellular Staphylococcus aureus in vitro and in vivo. IMT-P8 potentiates various antibiotics belonging to different classes. The best combination was found with clarithromycin; IMT-P8 modulated its activity by 256-fold. The IMT-P8 + clarithromycin combination showed excellent antibiofilm and intracellular pathogen-killing activity against MRSA GMCH 839. The remarkable effectiveness of IMT-P8 was demonstrated in murine superficial skin infection and sepsis survival models. The safety studies show that IMT-P8 exhibits no toxicity at its effective concentration in vitro and in vivo. These findings suggest that IMT-P8 could be a promising antibiotic adjuvant for treating severe bacterial infections caused by MRSA.

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IMT-P8对常规抗生素治疗耐药及细胞内金黄色葡萄球菌疗效的影响

在全球范围内，解决抗菌素耐药性问题至关重要。我们迫切需要创新的方法和替代新抗生素的发现，以解决日益严重的抗菌素耐药性问题。在这项研究中，我们研究了细胞穿透肽（IMT-P8）作为佐剂在体外和体内增强常规抗生素对多药耐药和细胞内金黄色葡萄球菌活性的作用。IMT-P8增强了属于不同类别的各种抗生素。与克拉霉素联合用药效果最佳；IMT-P8将其活性调节了256倍。IMT-P8 +克拉霉素组合对MRSA GMCH 839具有良好的抗菌膜和胞内杀灭活性。IMT-P8在小鼠浅表皮肤感染和脓毒症存活模型中显示出显著的有效性。安全性研究表明，IMT-P8在其有效浓度下，体外和体内均无毒性。这些发现提示IMT-P8可能是治疗MRSA引起的严重细菌感染的有希望的抗生素佐剂。

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来源期刊

ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES

CiteScore

9.70

自引率

3.80%

发文量

213

期刊介绍： ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.