Antimicrobial resistance (AMR) in agroecosystems is a critical global health challenge driven by the overuse of antibiotics in agriculture, accelerating the spread of antibiotic-resistant bacteria (ARB) and genes (ARGs) across environments and food chains. To contain this threat, the One Health framework is essential, coordinating surveillance and intervention across human, animal, and environmental sectors. Recent technological advances, particularly biosensor-based monitoring, enhance this integrated approach by enabling the rapid, on-site detection of both antimicrobial residues in food and water and ARGs in the environment, providing crucial real-time data. When aligned with multi-omics integration, AI-driven surveillance, and sustainable remediation strategies like bioremediation and biochar amendments, these tools offer transformative pathways for effective AMR management, strengthening antimicrobial stewardship and safeguarding both food security and public health.

BACKGROUND:Carbapenem-resistant Enterobacterales (CRE), particularly strains producing New Delhi metallo-β-lactamase (NDM), represent a critical global health threat and underscore an urgent need for effective NDM inhibitors. Allicin, a major bioactive compound in freshly crushed garlic, shows broad-spectrum antibacterial activity, but its detailed mechanisms and its capacity to reverse NDM-mediated carbapenem resistance remain to be fully elucidated. PURPOSE:This study aimed to evaluate the antibacterial effects of allicin alone and in combination with meropenem both in vitro and in vivo to uncover its mechanisms of action, thereby providing new mechanistic insights and a potential therapeutic strategy against NDM-mediated resistance. METHODS:The antibacterial activity of allicin and its mechanisms were assessed using microbroth dilution, membrane-permeability assays, ROS and H₂S detection, and comet assays. The in vivo efficacy was evaluated using a Galleria mellonella infection model and a rat Pasteurella pneumonia model. Synergy was assessed in vitro via checkerboard assays and in vivo using a rat wound infection model. The interaction with NDM-5 was studied through molecular docking, site-directed mutagenesis, enzyme kinetics, and microscale thermophoresis. RESULTS:Allicin exhibited potent activity against clinical isolates of Pasteurella and NDM‑positive Escherichia coli (MICs 8-64 μg/ml, MBCs 16-128 μg/ml) both in vitro and in vivo. It disrupted bacterial redox homeostasis by inducing ROS accumulation and suppressing endogenous H₂S production. Moreover, allicin restored meropenem activity both in vitro and in vivo and acted as a non‑competitive inhibitor of NDM‑5. Its disulfide bond covalently bound to key zinc‑coordinating residues in the active site, leading to Zn²⁺ release and the loss of NDM enzymatic activity. CONCLUSION:Allicin possesses a dual pharmacological role: exerting direct antibacterial activity through oxidative stress induction and reversing carbapenem resistance via the non‑competitive inhibition of NDM. These findings provide a promising lead compound for developing natural product-derived antibiotic adjuvants to address the global challenge of antimicrobial resistance (AMR).

Mobile genetic elements (MGEs) drive genome plasticity, horizontal gene transfer, and antimicrobial resistance (AMR) dissemination in Streptococcus, yet genus-wide comparisons across major MGE classes remain limited. Here, we analyzed 1961 complete chromosomes from 60 Streptococcus species together with 225 plasmids, and compared integrative and conjugative elements (ICEs), integrative and mobilizable elements (IMEs), prophages, and plasmids with respect to host distribution, boundary-supported integration-site preference, mobility-associated modules, representative backbones, and AMR cargo. We identified 1172 ICEs, 2362 IMEs, 3397 prophages, and 225 plasmids, and found that the streptococcal mobilome was strongly partitioned by host lineage, with ICEs and IMEs enriched in Streptococcus dysgalactiae, prophages in Streptococcus pyogenes, and plasmids in Streptococcus suis. Integrated MGEs also displayed class-specific hotspot hierarchies after boundary inspection: ICEs were highly concentrated at rplL, with secondary hotspots at rlmD and rpmH; IMEs were dominated by tRNA-associated sites together with rpsI and rpmG, whereas prophages occupied a broader hotspot spectrum centered on tRNA, rpmE, rpsD, hlpA, and mutL. Mobility analyses further distinguished the classes, showing that ICEs retained a narrow repertoire of conjugative backbones dominated by typeFATA, IMEs displayed the broadest relaxase diversity, and plasmids were mainly non-mobile or mobilizable. Representative family analyses resolved recurrent backbone types within each class, whereas AMR cargo was concentrated in ICEs and plasmids and was further stratified by host species. Together, these findings reveal a previously underappreciated class- and host-dependent organization of the streptococcal mobilome and its AMR cargo.

Transferable antimicrobial resistance poses significant threats to public health. This issue is further exacerbated by Lsa homolog-mediated resistance to pleuromutilins, lincosamides, and streptogramin A (PLSA). This study aimed to characterize a novel PLSA resistance gene, designated Lsa(F), identified in Streptococcus parasuis. The Lsa(F) protein exhibits 41.9–58.7

This review focuses on the research progress on natural products as β-lactam antibiotic adjuvants, aiming to address the escalating challenge of antibiotic resistance, particularly the inactivation of antibiotics caused by β-lactamases. The article provides an in-depth analysis of the mechanisms by which plant-derived (e.g., flavonoids, tannins, phenolics, terpenoids, and alkaloids) and microbial-derived (e.g., clavulanic acid, fungal metabolites, bacteriophages) natural products enhance antimicrobial efficacy. Key potentiation strategies discussed include efflux pump inhibition, membrane permeability alteration, biofilm disruption, PBP2a inhibition, and direct β-lactamase inhibition. Additionally, the review outlines in vitro methods (e.g., dilution and checkerboard assays) and in vivo models (e.g., mouse infection models) used to assess synergistic effects. It also addresses major challenges in identifying active compounds, elucidating mechanisms of action, and pharmacokinetic characterization. Looking forward, the article highlights the potential of multi-omics approaches, artificial intelligence, and nanotechnology to overcome existing bottlenecks, providing novel strategies for the development of effective and safe antibiotic adjuvants. These advances are expected to provide both theoretical insights and practical guidance for combating antibiotic-resistant bacterial infections.

Antimicrobial resistance (AMR) poses a major global public health threat. The low oral bioavailability of antibiotics in poultry, mediated by ATP-binding cassette (ABC) transporters, predisposes the host to subinhibitory conditions that exacerbate AMR transmission. However, earlier-generation ABC transporter inhibitors, such as verapamil and cyclosporine A, are limited by inherent hepatotoxicity. This study aimed to elucidate whether morin enhances the bioavailability of substrate drugs by inhibiting avian ABC transporters and to evaluate its potential in mitigating drug-induced liver injury (DILI). Using chicken embryo primary hepatocytes and chicken models, we investigated the inhibitory effects of morin on ABC transporter function and expression, and its impact on enrofloxacin oral bioavailability, through fluorescent substrate accumulation assays, molecular docking, and chicken xenobiotic receptor (CXR) reporter gene assays. Concurrently, employing an enrofloxacin and LPS co-induced liver injury model combined with oxidative stress markers, inflammatory cytokine detection, and histological analysis, we assessed the hepatoprotective effects of morin against DILI. Morin (60 mg/kg) significantly increased the oral bioavailability of enrofloxacin from 62.16% to 91.04% by directly inhibiting ABC transporter function and downregulating CXR-mediated transporter expression. Furthermore, morin effectively alleviated enrofloxacin-LPS-induced DILI through activation of the Nrf2-mediated antioxidant pathway and suppression of the NF-κB-mediated inflammatory response. In conclusion, morin functions as a novel dual-functional oral enhancer that not only boosts enrofloxacin bioavailability by inhibiting ABC transporters and downregulating their CXR-mediated expression but also confers hepatoprotection via the Nrf2/NF-κB pathways, thereby presenting a viable strategy to combat the AMR while ensuring drug safety in poultry production.

The global spread of multidrug-resistant (MDR) bacteria prompts the exploration of innovative antimicrobial strategies. Phage lysins—peptidoglycan hydrolases known for species-specific activity and low resistance potential—offer promising alternatives to conventional antibiotics. However, their typically narrow spectrum limits broad therapeutic application. To overcome this limitation, we leveraged the wide distribution of streptococcal mobilizable prophage (SMphage) families across Streptococcus species as a strategy to discover lysins with inherent broad-spectrum potential. Within these conserved prophages, we expressed PlyNJ3, an SMphage-derived endolysin homolog identified in S. suis, and evaluated its therapeutic efficacy in infection models. PlyNJ3 exhibited potent lytic activity against a broad panel of streptococci, including diverse S. suis clinical isolates (15 serotypes), 83.3

Macrolide antibiotics are commonly used to treat campylobacteriosis in both clinical settings and animal husbandry. The emergence of macrolide-resistant Campylobacter poses public health risks. In this study, six Campylobacter coli strains carrying erm(A) gene were identified from chicken cecum samples, and the functionality and genetic environment of erm(A) were analyzed. Antimicrobial susceptibility testing was conducted on Campylobacter isolates. WGS was used to analyze the genetic characteristics of erm(A)-positive strains. Cloning and in vitro-induced drug resistance assay were used to investigate the function of erm(A) gene. A total of 42 (20.2 %) C. coli isolates were obtained from 208 samples collected from chicken cecum, among which 6 erm(A)-positive. Induced drug resistance assay revealed a cytosine insertion at -54 bp/-55 bp in the erm(A) promoter, leading to a 4-fold increase in erythromycin MIC. WGS analysis showed that the erm(A) gene in C. coli shared high nucleotide sequence identity with that in Enterococcus faecalis and co-located with optrA between IS1216. To the best of our knowledge, this is a report of the prevalence and characterization of erm(A)-positive C. coli from chicken cecum. A cytosine insertion at -54 bp/-55 bp in the erm(A) promoter, leading to a 4-fold increased erythromycin MIC in Campylobacter coli.

Protein-based drug delivery systems offer advantages such as genetic tunability, structural homogeneity, and high biocompatibility. However, precisely controlling the assembly of protein nanoparticles and establishing correlations between their macroscopic properties and molecular architecture remain significant challenges. Here, inspired by chimeric collagen-like proteins, we rationally designed a series of de novo chimeric proteins comprising an N-terminal globular domain fused to a linear collagen-like domain. These structurally heterogeneous proteins were conjugated with doxorubicin (DOX) and homogenized to form chimeric collagen-like protein-DOX conjugated nanocomplexes (CDCNs). By fine-tuning the protein structure and domain organization, we achieved precise control over CDCN architecture and drug release kinetics. Furthermore, to enhance tumor specificity, triple-negative breast cancer (TNBC)- and glioblastoma (GBM)-targeting peptides were genetically fused to the chimeric proteins, respectively. In both in vitro and in vivo models of TNBC and GBM, CDCNs facilitated selective tumor accumulation, enhanced cellular uptake, and promoted apoptosis while minimizing off-target toxicity. This work establishes a strategy for designing protein-based nanoplatforms with programmable structures and tunable functionalities, offering promising potential for precisely controlling of protein-based delivery system.

Breast cancer resistance protein (BCRP) efflux activity limits drug absorption and contributes to multidrug resistance. Targeting nuclear receptors to modulate BCRP expression offers a potential strategy to overcome this challenge. Although it is known that the chicken xenobiotic receptor (CXR) influences BCRP expression, the exact binding site and mechanism remain unclear. This study aims to clarify how CXR regulates BCRP transcription in chickens and to find natural CXR inhibitors to improve the absorption of BCRP-substrate drugs. Utilizing a dual-luciferase reporter assay, we identified a functional CXR response element located between -9567 and -9551 upstream of the chicken BCRP transcriptional start site. Using this element, a screening model was developed, which revealed that quercetin inhibits CXR transcriptional activity in a concentration-dependent manner. In vitro experiments demonstrated that quercetin significantly downregulated BCRP mRNA expression and reduced efflux efficiency in chicken hepatocytes. In vivo studies further confirmed that quercetin decreased BCRP expression in liver, kidney, and intestine. Furthermore, the use of a jejunal perfusion model showed that quercetin (20 mg/kg) significantly increased the apparent permeability coefficient of the BCRP substrate florfenicol from 0.32 to 0.59 (p < 0.01). Subsequent pharmacokinetic analyses revealed that coadministration with quercetin (20 mg/kg) significantly elevated the Cmax from 7.24 to 10.00 μg/mL (p < 0.01) and the AUC0-∞ from 25.09 to 44.60 h·μg/mL (p < 0.01) of florfenicol. This research elucidates the molecular mechanisms underpinning the CXR-BCRP transcriptional cascade and proposes an innovative strategy targeting nuclear receptors to enhance drug absorption.

Streptococcus suis is a major zoonotic pathogen, with penicillins being the first-line treatment for S. suis infections. However, increasing reports of penicillin-non-susceptible (PNS) S. suis have raised concerns, yet the underlying resistance mechanisms remain poorly understood. In this study, we analyzed 107 PNS S. suis isolates to investigate the genetic and phenotypic basis of penicillin resistance. Antimicrobial susceptibility testing revealed that PNS S. suis isolates exhibited higher resistant rates to a number of antimicrobials, including tetracyclines, macrolides and lincosamides. Indeed, high-level penicillin-resistant (HLPR) isolates exhibited even higher resistant rates to these antimicrobials. Serotyping and multilocus sequence typing (MLST) revealed the presence of diverse genetic backgrounds, indicating a potential for widespread transmission. A detailed amino acid analysis of penicillin-binding proteins (PBPs) identified specific substitutions in PBP2x-M341I, I373V, and M401I-associated with HLPR. Recombinant expression of PBP2x proteins containing these substitutions allowed further investigation of their binding affinity to β-lactam antibiotics. Acylation efficiency assays revealed that the M341I substitution significantly reduced the binding affinity of PBP2x for penicillins but not for cephalosporins. These findings provide new insights into the molecular mechanisms underlying HLPR in S. suis and underscore the importance of PBP2x substitutions in driving penicillin resistance.

This study elucidated the mechanisms underlying the immunoregulatory and gut-microbiota-modulating effects of Flammulina velutipes residue polysaccharide (FVRP) using cyclophosphamide (CTX)-induced mouse models. FVRP supplementation alleviated CTX-induced intestinal damage and boosted antioxidant enzyme activity and cytokine secretion. Additionally, FVRP enhanced the diversity and total species richness of the gut microbiota, promoting the proliferation of beneficial bacteria (e.g., Prevotellaceae), while reducing the abundance of CTX-derived bacteria (Lachnospiraceae and Rikenellaceae). FVRP facilitates the accumulation of short-chain fatty acids. Untargeted metabolomic analyses of cecal content revealed that FVRP treatment notably restored the levels of 32 endogenous metabolites altered by CTX. Based on a pseudosterility mice model, fecal microbiota transplantation (FMT), and fecal filtrate transplantation (FFT), gut microbiota and associated metabolites were demonstrated to play a crucial role in the immunomodulatory and protective effects of FVRP against intestinal injury. In conclusion, FVRP exhibits significant potential as an immune enhancer and natural therapeutic agent for alleviating intestinal inflammatory conditions.

Antimicrobial resistance poses a significant threat to global health, particularly with multidrug-resistant (MDR) Gram-positive pathogens evading last-line treatments. We herein designed and synthesized novel amphiphilic lipopeptide derivatives to exert dual antibacterial mechanisms: SPase I inhibition and bacterial membrane disruption. Among these, compound A09 demonstrated potent in vitro activity against a series of MDR Gram-positive pathogens. Biochemical characterization revealed potent inhibition of Escherichia coli SPase I (LepB) with an IC50 of 4.475 μM and a Kd of 16.3 ± 11.4 μM. Mechanistic studies confirmed A09's membrane disruption and significant biofilm eradication capability. Critically, A09 exhibited substantial efficacy in vivo in a murine model of methicillin-resistant Staphylococcus aureus (MRSA) skin infection. Furthermore, A09 displayed low hemolytic and cytotoxic effects, indicating a favorable safety profile. These results established A09 as a promising dual-mechanism anti-infective agent for treating drug-resistant Gram-positive infections.

The valproic acid (VPA), an anti-epileptic drug, has demonstrated anticancer properties alone or in combination regimens in glioma. It has been shown synergistic activity with cisplatin in resistant cancer cells. In the current study, we synthesized Pt(II) complexes bearing VPA as ancillary/leaving ligand. All these complexes were obtained in good yields through simple reproducible synthetic procedures and characterized by multiple analytical techniques in both solution and solid state. In situ release of ancillary ligand (VPA) by these complexes was studied by 1H NMR in solution state that was catalysed by water in time dependent manner. The tumor preferential selective VPA-Pt actively controlling NF-kB signaling, culminating in the attenuation of IL-6 expression and the concomitant activation of p53 and caspase-3 pathways in gliomas. VPA-Pt exhibits potent cytotoxicity in human and mice glioma cancer cell lines, inducing apoptosis as evidenced by inhibition of cell proliferation and migration, disruption of mitochondrial membrane potential, and suppression of colony formation. An inhibitory effect of VPA-Pt4 on glioma was clearly evidenced through in vivo live bioluminescence imaging, histopathological examination, immunofluorescence evaluation, and protein expression analysis demonstrated that VPA-Pt4 significantly triggered apoptosis, with elevated levels of P53, caspase-3, cleaved caspase-3, along with a reduction in IL-6. Our discovery reveals a novel and efficient approach to glioma therapy.

Antimicrobial peptides (AMPs) are promising candidates to address the global antimicrobial resistance crisis, yet their traditional design remains labor-intensive and inefficient. Here, we developed BroadAMP-GPT, an integrated computational-experimental framework that combines AI-driven generation, multi-tiered screening, and experimental validation to rapidly discover potent AMPs with broad-spectrum activity. Using this platform, 57% of AI-generated candidates exhibited potent efficacy against ESKAPE pathogens - key culprits of multidrug-resistant infections. An outstanding candidate, AMP_S13, demonstrated exceptional stability under diverse physiological conditions, including extreme pH (2-10), proteolytic exposure, and elevated temperatures, while maintaining minimal cytotoxicity and low hemolytic activity. AMP_S13 also showed robust in vivo efficacy, reducing mortality in Galleria mellonella infection model and accelerating wound healing in a murine MRSA skin infection model. These results validate BroadAMP-GPT as a transformative tool for accelerating the discovery of stable, broad-spectrum and low-toxicity AMPs, offering a scalable strategy to address the urgent threat of multidrug-resistant pathogens.

Linezolid and penicillin are critical for treating multidrug resistant (MDR) Gram-positive infections, but the emergence of resistance to both seriously threatens public health. Here, we first report the cocarrying poxtA (oxazolidinone resistance) and pbp5fm (β-lactam resistance) genes by the plasmid in a strain of Enterococcus hirae HDC14-2 derived from porcine. The isolate also exhibits MDR phenotypes to phenicols, oxazolidinones, tetracyclines, β-lactams, aminoglycosides, macrolides, and lincosamides. Whole-genome sequencing (WGS) revealed these resistance genes, along with tet(L), tet(M), catA, erm(B), aac(6)-aph(2"), aadE, spw, lsa(E), lnu(B), sat4, and aphA3, were clustered in a novel MDR region flanked by IS1216 elements on plasmid pHDC14-2.133K. This IS1216-bounded MDR region formed translocatable units (TUs), including an IS1216-poxtA TU that was also identified on a secondary plasmid, pHDC14-2.27K. Functional assays demonstrated the excisability and mobility of these TUs, indicating its potential ability integration into other plasmids or chromosomes. Critically, electrotransformation confirmed the transfer of pHDC14-2.27K (poxtA-carrying) to Enterococcus faecalis JH2-2, with retained TU activity and minimal fitness cost. This study provides the evidence of colocalized poxtA and pbp5fm on plasmids in enterococci, highlighting their role in disseminating pan-resistance among bacteria. Although E. hirae is not an important pathogenic bacterium to humans and animals, but its potential risk to horizontally spread of these resistance genes important in medicine still cannot be ignored.

Objectives To investigate the genetic context and transferability of the oxazolidinone resistance gene optrA in a Streptococcus parasuis isolate.Methods The optrA-carrying S. parasuis isolate SFJ45 was characterized by PCR, antimicrobial susceptibility testing, complete genome sequencing and bioinformatic analysis. The transferability of optrA was verified by conjugation, followed by SmaI-PFGE and Southern blotting.Results The S. parasuis isolate SFJ45 was positive for optrA, mef(A), msr(D), erm(B), tetAB(P)', tet(M), aadE, aphA3, catQ, dfrG and mdt(A), conferring an MDR phenotype. The optrA gene was flanked by ISS1N at both termini in the same orientation, representing a novel 8750 bp pseudo-compound transposon, organized as the ISS1N-hth-clb-4hp-optrA-2hp-ISS1N structure. The ISS1N-optrA-carrying transposon was further inserted within an integrative and conjugative element, ICESpsuSFJ45, at 3 ' end of the fda gene. Conjugative transfer of the ISS1N-optrA-carrying transposon with ICESpsuSFJ45 was observed from S. parasuis to Streptococcus suis at a frequency of (1.01 +/- 3.12) x 10-7.Conclusions ISS1N was found to be associated with optrA spreading for the first time. Integration of the ISS1N-optrA transposon within ICESpsuSFJ45 may lead to the co-selection of optrA with other antimicrobial resistance genes, contributing to its horizontal transfer from S. parasuis to clinically more important bacterial pathogens.

Oxidative stress frequently contributes to intestinal barrier injury in animals and humans. It was reported that both Selenomethionine (SeMet) and allicin exhibit protective effects against a range of diseases caused by oxidative stress. This study aimed to investigate the synergistic antioxidant effects and underlying mechanisms of SeMet and allicin on a H2O2-induced intestinal barrier injury model using IPEC-J2 cells and mice. The results showed that H2O2 induced severe oxidative stress, including a decrease in cell viability, antioxidant level, migration capacity, and cell integrity. SeMet and allicin exhibited significant synergistic anti-oxidative effects on intestinal epithelial cells. The combined use of SeMet and allicin increased SOD activity, GSH content, and GSH/GSSG ratio while decreasing MDA, NO, and ROS content levels. Furthermore, we found that SeMet and allicin synergistically activated the nuclear factor erythroid-related factor 2 (Nrf2)-NAD(P)H dehydrogenase [quinone] 1 (NQO1) signaling pathway and down-regulated endoplasmic reticulum stress (ER stress)-related proteins. However, the synergistic antioxidative and intestinal barrier protective effects of SeMet and allicin were abolished by Nrf2 inhibitor ML385 in vitro and in vivo. In conclusion, SeMet and allicin synergistically attenuate intestinal barrier injury induced by excessively oxidative stress through the activation of the Nrf2 signaling pathway and inhibition ER stress. These findings support that the combined use of SeMet and allicin could enhance antioxidative properties and alleviate intestinal injury in further clinical practice.

Campylobacter spp., such as Campylobacter jejuni and Campylobacter coli, are important zoonotic Gram-negative pathogens that cause acute intestinal diseases in humans. In this study, a retrospective analysis was conducted on previously collected Campylobacter isolates from antimicrobial resistance surveillance. A total of 29 optrA-positive C. coli strains were identified and subjected to second-generation sequencing. Multilocus sequence typing and single nucleotide polymorphism analyses demonstrated that the 29 optrA-positive isolates were genetically homogeneous. Notably, among the 29 isolated strains, the ΔoptrA variants exhibit a nonsense mutation at position 979 where the base C is substituted by T, leading to the formation of a premature termination codon. The alignment of sequences and genetic environmental characteristics suggested that ΔoptrA located on a chromosomally carried multidrug-resistant genomic island. There are other resistant genes on the multidrug resistance genomic island, such as aph(2'')-If, aph(3')-III, aadE, tet(O), tet(L), cat, erm(A), optrA and blaOXA-61. As a result, the 29 ΔoptrA-positive strains displayed susceptibility to both florfenicol and linezolid. The ΔoptrA gene is linked to the erm(A) gene, resulting in the formation of translocatable unit (TU) that are encompassed by two copies of IS1216 mobile elements. Multiple occurrences of similar TUs have been documented in numerous C. coli and provided evidence for the significance of TUs in facilitating the transfer of drug resistance genes in C. coli.

The administration of drugs via the oral route is challenging due to the presence of physiologic barrier. BCRP, which can actively transport substrates from intra- to extracellular environment, has an important functional role in the composition of physiologic barrier. Therefore, overcoming BCRP efflux is a strategy to improve the absorption of substrate drugs. Curcumin is a natural feed additive for poultry health and production. However, it is unknown whether curcumin affects the expression of BCRP. The purpose of this study was to investigate the role of curcumin in the regulation of BCRP and its influences on pharmacokinetics of BCRP substrate florfenicol. Results showed that curcumin (60 m M) inhibited the expression of BCRP mRNA by 58% and BCRP protein by 52% in primary chicken hepatocytes. Moreover, intracellular mitoxantrone (a selective BCRP substrate) fluorescence was 1.58-fold higher in cells pretreated with 60 m M curcumin than in untreated cells, indicating that curcumin inhibited the transport function of BCRP. In vivo experiments showed that curcumin reduced BCRP expression in the liver, kidney, duodenum, jejunum and ileum of chicken. Coadministration of curcumin (150 mg/kg) significantly changed the pharmacokinetic behavior of orally administered florfenicol (substrate of chicken BCRP), with a higher area under the curve (35.51 vs. 25.81 h cent ug/L) and a higher C max values (9.94 vs. 7.61 m g/mL). The bioavailability of orally administered florfenicol was increased from 51.6 to 72.8% by curcumin. Together, our results indicate that curcumin inhibited the expression and efflux function of BCRP in chicken and improved the bioavailability of BCRP substrate florfenicol.