Chitosan-dextran sulfate nanocapsules for enhanced tigecycline efficacy against non-typhoidal Salmonella enterica.

Abstract

UNLABELLED: is a significant foodborne pathogen found worldwide. Resistance to tigecycline (TGC) has been increasingly reported. The emergence of multidrug-resistant (MDR) non-typhoidal (NTS) with high efflux pump activity necessitates the development of efficient drug delivery systems. This study investigates the potential of tigecycline-loaded chitosan-dextran sulfate (CD-TGC) nanocapsules to combat NTS in vitro and in vivo mouse peritonitis model. Antimicrobial susceptibility and efflux pump activity of NTS isolates were tested. serotype Bredeney isolates that showed high efflux index and high multiple antibiotic resistance index were subjected to whole genome sequencing (WGS), revealing numerous resistance genes, including APH(3’’), A, rB, R, , , , C, AcrAB-TolC, AcrAD-TolC, B, D, A, H-NS, and R. Additionally, the presence of resistance-nodulation-cell division (RND) efflux pumps, major facilitator superfamily (MFS), and ATP-binding cassette (ABC) efflux pumps were confirmed. CD-TGC demonstrated significantly lower minimum inhibitory concentrations (MIC 0.5–1 µg/mL) against NTS strains compared to tigecycline (TGC) alone (MIC 32–128 µg /mL). CD-TGC decreased MIC 7-fold, from 128 to 1 µg/mL, in one Typhimurium strain. In the other 11 strains, CD-TGC reduced the TGC MIC 6-fold, from 64 to 1 µg/mL ( = 6) and 32 to 0.5 µg/mL ( = 5). Time-kill assays confirmed enhanced bactericidal activity. Furthermore, CD-TGC downregulated the expression of and efflux pump genes. In a mouse model of Typhimurium infection, CD-TGC treatment effectively reduced bacterial burden in the liver and intestine, minimized liver and kidney function alterations, and decreased mortality rates compared to tigecycline and unloaded CD nanocapsules. The survival rates of mice were 100% in the CD-TGC treatment group and 40% in the TGC treatment group. Histopathological analysis confirmed reduced tissue damage in the CD-TGC-treated group. The findings indicate that CD-TGC nanocapsules offer a promising drug delivery strategy for treating intracellular infections, overcoming resistance mechanisms and improving treatment outcomes where tigecycline alone is less effective. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-35229-7.

AI evidence extraction

Main findings

Tigecycline-loaded chitosan–dextran sulfate nanocapsules (CD-TGC) showed substantially lower MICs (0.5–1 µg/mL) against NTS strains than tigecycline alone (32–128 µg/mL) and enhanced bactericidal activity in time-kill assays. In a mouse Typhimurium infection model, CD-TGC reduced bacterial burden in liver and intestine, was associated with fewer liver/kidney function alterations, reduced tissue damage, and higher survival (100% vs 40% with tigecycline).

Outcomes measured

• Minimum inhibitory concentration (MIC) against non-typhoidal Salmonella enterica strains
• Time-kill assay bactericidal activity
• Efflux pump activity and efflux pump gene expression
• Mouse peritonitis model outcomes: bacterial burden (liver, intestine)
• Mouse survival/mortality
• Liver and kidney function alterations
• Histopathology/tissue damage

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    "study_type": "animal",
    "exposure": {
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        "source": null,
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    },
    "population": null,
    "sample_size": null,
    "outcomes": [
        "Minimum inhibitory concentration (MIC) against non-typhoidal Salmonella enterica strains",
        "Time-kill assay bactericidal activity",
        "Efflux pump activity and efflux pump gene expression",
        "Mouse peritonitis model outcomes: bacterial burden (liver, intestine)",
        "Mouse survival/mortality",
        "Liver and kidney function alterations",
        "Histopathology/tissue damage"
    ],
    "main_findings": "Tigecycline-loaded chitosan–dextran sulfate nanocapsules (CD-TGC) showed substantially lower MICs (0.5–1 µg/mL) against NTS strains than tigecycline alone (32–128 µg/mL) and enhanced bactericidal activity in time-kill assays. In a mouse Typhimurium infection model, CD-TGC reduced bacterial burden in liver and intestine, was associated with fewer liver/kidney function alterations, reduced tissue damage, and higher survival (100% vs 40% with tigecycline).",
    "effect_direction": "benefit",
    "limitations": [],
    "evidence_strength": "low",
    "confidence": 0.7399999999999999911182158029987476766109466552734375,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "tigecycline",
        "chitosan-dextran sulfate",
        "nanocapsules",
        "drug delivery",
        "non-typhoidal Salmonella enterica",
        "multidrug resistance",
        "efflux pumps",
        "mouse peritonitis model",
        "MIC",
        "time-kill assay",
        "whole genome sequencing"
    ],
    "suggested_hubs": []
}

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