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A total of 1040 fecal samples, collected from 12 dairy cattle farms in Hebei and Tianjin, near the Bohai area of China, were screened for Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi by polymerase chain reaction. The overall prevalence for Cryptosporidium , G. duodenalis and E. bieneusi was 1.0% (n = 10), 4.7% (n = 49) and 19.4% (n = 202), respectively. Ten Cryptosporidium -positive samples were identified as C. parvum by DNA sequence analysis of the small subunit rRNA (SSU rRNA) gene. DNA sequencing of the 60-kDa glycoprotein gene revealed that the C. parvum samples were all subtype IIdA19G1. Forty-nine G. duodenalis -positive samples belonged to assemblage E (n = 47) and assemblage E mixed with A (n = 2), based on the sequenced SSU rRNA, triosephosphate isomerase, and glutamate dehydrogenase genes. Sequence analysis of the internal transcribed spacer (ITS) gene identified six known E. bieneusi genotypes, I (n = 87), J (n = 83), BEB4 (n = 18), BEB6 (n = 3), N (n = 1) and Ebpc (n = 1), along with three new genotypes, CHC6 (n = 1), CHC7 (n = 1) and CHC8 (n = 7). Phylogenetic analysis showed that Ebpc belonged to zoonotic group 1, whereas the other E. bieneusi genotypes clustered within group 2. More studies are needed to better understand the species distributions and public health significance of these pathogens in the study areas. [ABSTRACT FROM AUTHOR]

Genetic variations in microRNAs (miRNAs) including primary miRNAs, precursor miRNAs and mature miRNAs can lead to phenotypic variation by altering the biogenesis of miRNAs and/or their binding to target mRNAs. Increasing functional studies suggest that polymorphisms occurring in miRNAs can lead to phenotypic variation in farm animal. Here, we identified a single nucleotide polymorphism (SNP) located in the precursor of chicken miRNA-1606 gene. The association study on body indexes, body weight at different growth stages, and carcass traits was performed in a Gushi–Anka F 2 population resource. The SNP was not only significantly associated with body weight at 10 and 12 weeks, respectively, but also with chicken shank length, chest depth and body slanting length at 8 weeks; shank length, pectoral angle, body slanting length and pelvis breadth at 12 weeks, respectively. And the polymorphism was also significantly associated with carcass traits including semi-evisceration weight, evisceration weight, breast muscle weight, leg weight and carcass weight as well. The observed values of individuals with CA genotype were significantly higher than CC genotype both in body weight at different stages and carcass traits. This SNP altered the predicted second structure of pre-mir-1606, with the altering of the free energy values. And the relative expression level of mature miRNA between CA and AA was significantly changed in leg muscle. Our data suggested that miRNA-1606 may be a candidate gene associated with chicken growth traits. [ABSTRACT FROM AUTHOR]

Stress-induced immunosuppression (SIIS) is one of the common problems in intensive poultry production, which brings enormous economic losses to the poultry industry. Accumulating evidence has shown that microRNAs (miRNAs) were important regulators of gene expression in the immune system. However, the miRNA-mediated molecular mechanisms underlying SIIS in chickens are still poorly understood. This study aimed to investigate the biological functions and regulatory mechanism of miRNAs in chicken SIIS. A stress-induced immunosuppression model was successfully established via daily injection of dexamethasone and analyzed miRNA expression in spleen. Seventy-four differentially expressed miRNAs (DEMs) was identified, and 229 target genes of the DEMs were predicted. Functional enrichment analysis the target genes revealed pathways related to immunity, such as MAPK signaling pathway and FoxO signaling pathway. The candidate miRNA, gga-miR-146a-5p , was found to be significantly downregulated in the Dex-induced chicken spleen, and we found that Dex stimulation significantly inhibited the expression of gga-miR-146a-5p in Chicken macrophages (HD11). Flow cytometry, 5-ethynyl-2′-deoxyuridine (EdU), cell counting kit-8 (CCK-8) and other assays indicated that gga-miR-146a-5p can promote the proliferation and inhibit apoptosis of HD11 cells. A dual-luciferase reporter assay suggested that the Interleukin 1 receptor associated kinase 2 (IRAK2) gene, which encoded a transcriptional factor, was a direct target of gga-miR-146a-5p , gga-miR-146a-5p suppressed the post-transcriptional activity of IRAK2. These findings not only improve our understanding of the specific functions of miRNAs in avian stress but also provide potential targets for genetic improvement of stress resistance in poultry. • A total of 74 DEMs were obtained by RNA-seq and a total of 229 target genes of DEMs were predicted. • Gga-miR-146a-5p promoted the proliferation and inhibited the apoptosis of HD11 cells. • IRAK2 was target gene of gga-miR-146a-5p and inhibited by gga-miR-146a-5p. • Gga-miR-146a-5p regulates stress-induced immunosuppression in chicken by targeting the IRAK2 Gene. [ABSTRACT FROM AUTHOR]

Abstract: Whole proteins of the second-generation merozoite of Eimeria tenella were analyzed by two-dimensional gel electrophoresis (2-DE) and western blot using the chicken sera infected artificially with E. tenella. Approximately 640 spots were detected on proteome map of the second-generation merozoite stained by Coomassie brilliant blue G-250 and 85 spots were recognized on western blot map as antigens. Forty four spots of the antigens were identified by matrix-assisted laser desorption ionization time-of-flight MS (MALDI-TOF-MS) and MALDI-TOF-TOF-MS. Twenty six proteins of E. tenella and three homologous proteins to other apicomplexan parasites or protozoan were identified using ‘Mascot’ server. These proteins included lactate dehydrogenase, enolase, 14-3-3 protein, microneme proteins, tubulin beta chain, SERPIN1 protein precursor, large subunit ribosomal protein L23 and surface antigens of E. tenella, heat shock protein (HSP70) of Eimeria acervulina, protein phosphatase type 1 of Toxoplasma gondii and hypothetical protein GSPATT00020155001 of Paramecium tetraurelia. The rest proteins were searched against the E. tenella protein sequence database using ‘Mascot in-house’ (version 2.1) search engine in automated mode and 11 unknown proteins were identified. After the amino acid sequence of the unknown proteins were searched using BLAST against non-redundant sequence databases (NCBI), surface antigen 12 of E. tenella and six homologous proteins to other apicomplexa parasites were found. They were membrane skeleton protein IMC2A, mitochondrial F1-ATP synthase beta subunit precursor, 3-oxoacyl-acyl-carrier-protein synthase and catalase of T. gondii, Vps26 of Plasmodium falciparum 3D7, and hypothetical protein TRIADDRAFT_60424 of Trichoplax adhaerens. No homologues of 8 spots of the 44 analyzed proteins were found. These proteins enriched the data of immunogenic proteins of the second-generation merozoite of E. tenella. [Copyright &y& Elsevier]

• Dexamethasone-Induced immunosuppression models were constructed in Gushi cocks. • MiR-103-3p, miR-456-3p and miR-15/17 family were essential miRNAs. • Some DEGs, such as SIKE1 , HMGA2 , IL6 , SOCS3 , ITGB5 were crucial mRNAs. • Gga-miR-20b-5p negatively regulated SIKE1 may play a role in immunosuppression. Stress-induced immunosuppression is a serious problem affecting the production value of poultry, but its specific molecular mechanism has not yet been elucidated. We selected 7-day-old Gushi cocks as test animals and successfully established a stress-induced immunosuppression model by injecting 2.0 mg/kg (body weight) dexamethasone (Dex). We then constructed six cDNA libraries and two small RNA libraries of Bursa of Fabricius from the control group and the Dex group. RNA-seq results revealed 21,028 transcripts including 3920 novel transcripts; 500 miRNAs including 68 novel miRNAs were identified. Correlation analysis of miRNA, target genes and mRNA results indicated that the gga-miR-15 family, gga-miR-103-3p, gga-miR-456-3p, and gga-miR-27b-3p, as core differentially expressed miRNAs, may potentially regulate multiple genes which are involved in immune-related pathways; and that the core genes Suppressor of IKBKE 1 (SIKE1) and high mobility group AT-hook 2 (HMGA2) are associated with the miR-17 family (gga-miR-20a-5p, gga-miR-20b-5p, gga-miR-106-5p, and gga-miR-17-5p) and gga-let -7 family (gga-let-7b, gga-let-7i, gga-let-7c-5p, and gga-let-7f-5p). The interaction networks of mRNAs of significantly enrichment pathways and PPI (protein-protein interaction) networks showed that IL6 , IL1B , IL8L1 , CCL5 , SOCS3 , SOCS1 , ITGB5 , GSTA3 , SQLE , FDFT1 , FN1 , IL18 , IL10, MAPK11 and MAPK12 are network core nodes and that most of them are strongly associated with immune response. One of the candidate miRNAs, gga-miR-20b-5p, may play an important role in stress-induced immunosuppression. Luciferase assay and over-expression experiments suggested that gga-miR-20b-5p negatively regulated the expression of target gene SIKE1. These results provide better understanding of the mechanism of stress-induced immunosuppression in Gushi chicken bursa, and provide novel targets for subsequent research to improve poultry anti-stress capability. [ABSTRACT FROM AUTHOR]

In recent years, increasing interest has focused on natural components extracted from plants, among which plant polysaccharides as natural immunomodulators that can promote animal immunity. The present study was performed to investigate the effect of feed supplement Pseudostellaria Heterophylla Polysaccharide (PHP) on serum Immunoglobulins, T lymphocyte subpopulations, Cytokines and Lysozyme (LZM) activity in chicks. In addition, the influence of PHP on splenic gene expression was investigated by transcriptome sequencing. Four hundred 7-day-old Gushi cocks were randomly divided into four groups in a completely randomized design. The chicks were fed with a basal diet supplemented with 0 (CON-A), 100 (PHP-L), 200 (PHP-M) and 400 (PHP–H) mg/kg PHP. Blood and spleen samples were collected from 6 randomly selected chicks in each group at 14, 21, 28, and 35 days of age. The results showed that compared to the CON-A group, the PHP-M group exhibited significant increases in the levels of IgA, IgG, IgM, CD3, and LZM in the serum at 14, 21, 28, and 35 days (P < 0.05), and at 28 d, there was a significant quadratic relationship between the levels of dietary PHP and the levels of IgG, IgM, IFN-γ, IL-2, CD3, and LZM. Furthermore, a total of 470 differentially expressed genes (DEGs) were identified in spleen from PHP-M and CON-A at 28 d. These DEGs were significantly enriched in the Phagosome, Intestinal immune network for IgA production and Cytokine-cytokine receptor interaction pathways. The present investigation highlights the ameliorating effect of dietary PHP on immunological variables and spleen of chicks, the study suggests that PHP supplementation can enhance immunity and positively impact spleen mRNA expression in chicks. • Pseudostellaria Heterophylla Polysaccharide exerts immuno enhancement effect for the chicks. • The optimal dietary level of Pseudostellaria Heterophylla Polysaccharide for chicks was 200 mg/kg. • The expression of immune-related genes in the spleen could be regulated by Pseudostellaria Heterophylla Polysaccharide. [ABSTRACT FROM AUTHOR]

Adiponectin is a hormone secreted by adipose tissue that is involved in the regulation of energy homeostasis and reproduction. In this study, the expression levels of adiponectin and its receptors in the hypothalamic-pituitary-ovarian (HPO) axis of laying hens were investigated using quantitative real-time PCR (qRT-PCR) and Western blotting, and the localization of these proteins was explored using immunohistochemistry. The morphological relationships between adiponectin receptors and gonadotropin-releasing hormone (GnRH) neurons were analyzed using double immunofluorescence labeling. The results showed that adiponectin mRNA and protein were widely expressed in all tissues involved in the HPO axis in laying hens, with especially high expression in the hypothalamus. Both AdipoR1 and AdipoR2 were more highly expressed in the pituitary than in other tissues and exhibited similar mRNA and protein expression patterns. The immunohistochemistry results showed that adiponectin and AdipoR2 were localized in the major hypothalamic nuclei that regulate food intake and energy balance (i.e., the lateral hypothalamic area (LHA), infundibular nucleus (IN), dorsomedial nucleus (DMN), and paraventricular nucleus (PVN)). Immunostaining revealed that adiponectin and its receptors were also localized in the cytoplasm of cells in the adenohypophysis. In the ovaries, adiponectin was localized in the granulosa layer, in the theca externa of follicles and in basal cells, while AdipoR1 and AdipoR2 were localized in basal cells. In the double immunofluorescence labeling experiment, AdipoR1 and AdipoR2 were localized in GnRH neurons in the IN and DMN. These results suggest that adiponectin and its receptors may play major roles in the endocrine network, which integrates energy balance and reproduction. • Adiponectin was highly expressed at the mRNA and protein levels in the hypothalamus. • AdipoR1 and AdipoR2 were more highly expressed in the pituitary and exhibited similar mRNA and protein expression patterns. • Immunostaining revealed the localization of adiponectin and AdipoR2 in the major hypothalamic nuclei. • The colocalization of adiponectin receptors with GnRH neurons in the hypothalamic regions of IN, DMN, MM, and IH. • Adiponectin and its receptors were localized in the adenohypophysis. • Adiponectin was localized in the granulosa layer, theca externa of follicles and ovarian basal cells. • AdipoR1 and AdipoR2 were localized only in ovarian basal cells. [ABSTRACT FROM AUTHOR]

• 7-day-old Gushi cocks stress model was successfully constructed by adding corticosterone (CORT) 30 mg/kg basic diet for 7 days. • A total of 269 CORT-induced spleen significantly differentially expressed genes were obtained by RNA-seq. • HSPA8, HSPA2 and IL8L1 may play important roles in the regulation of CORT-induced stress effects on immune function. Stress is a physiological manifestation of the body's defense against adverse effects of external environment, but the molecular regulatory mechanism of stress effects on immune function of poultry has not been fully clarified. In this study, 7-day-old Chinese local breed Gushi cocks were used as model animal, and the stress model was successfully constructed by adding corticosterone (CORT) 30 mg/kg basic diet for 7 days. The spleen transcriptomes of the control group (B_S group) and the stress model group (C_S group) was determined by high-throughput mRNA sequencing (RNA-Seq) technology, and a total of 269 significantly differentially expressed genes (SDEGs) were obtained (P adj < 0.05, |FC| ≥ 2 and FPKM > 1). Compared with B_S group, there were 140 significantly up-regulated genes and 129 significantly down-regulated genes in C_S group. The immune/stress-related Gene Ontology (GO) terms included positive regulation of T cell mediated immunity, chemokine-mediated signaling pathway, T cell mediated immunity and so on. The SDEGs such as IL8L1 , HSPA8 , HSPA2 , RSAD2 , CCR8L and DMB1 were involved in these GO terms. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that the SDEGs participated in many immune-related signaling pathways. The immune-related genes HSPA2 , HSPA8 , HSP90AA1 , HSPH1 and HERPUD1 were enriched in Protein processing in endoplasmic reticulum pathway, IL8L1 , CXCL13L2 , CCR6 , LEPR , CCR9 and CCR8L were enriched in Cytokine-cytokine receptor interaction pathway. The protein-protein interactions (PPI) analysis showed HSPA8 , HSPA2 and IL8L1 as key core nodes had 7 interactions and may play important roles in the regulation of CORT-induced stress effects on immune function. The data onto this study enriched the genomic study of stress effects on immune function, and provided unique insights into the molecular mechanism of stress effects on immune function, and the genes identified in this study can be candidates for future research on stress response. [ABSTRACT FROM AUTHOR]

The large economic losses caused by leg disorders have raised concerns in the broiler industry. Several types of leg disorders in broilers have been identified, such as tibial dyschondroplasia (TD), femoral head necrosis (FHN), and valgus-varus deformity (VVD). In this study, phenotypic changes associated with VVD were examined using clinical diagnosis, anatomical examination, measured growth performance, bone traits, and serum indicators. The incidence of VVD among the chicken population at a commercial facility in Tangshan China was 1.75% (n = 52,000), distributed about 1:1 (n = 122), between females and males. A majority of chickens were characterized by a unilaterally abnormality, while appropriately 17.6% by bilateral abnormality. Approximately 97.9% of affected broilers were classified as the "valgus" type. Growth traits, including body weight, shank length, and shank girth, were significantly lower in chickens with VVD, while tibia and metatarsal bone indexes were about 1.3-fold higher in the affected birds than in the normal birds. Bone mineral density, bone breaking strength, and several serum indicators were significantly different between affected and normal broilers. Sparse and disarranged bony trabecular was observed in abnormal broilers by histological analysis. Generally, leg disorders are associated with compromised growth, bone quality, bone structure, and lipid metabolism. This study provides a reference for clinical diagnosis of VVD and lays a foundation for exploring its underlying mechanisms. [ABSTRACT FROM AUTHOR]

The reproductive performance of breeder roosters has significant economic importance in the poultry industry. Breeder roosters have severely reduced semen quality with age and will be at risk of culling in the following years. In order to extend the use of breeder roosters, we drew on the induced molting model of hens and selected 35 Houdan roosters aged 50 wk for induced molting. By comparing the body weight, testicular weight, semen quality, and reproductive performance before and after induced molting, we found that induced molting could restore the body weight and testicular weight to the levels before molting (P > 0.05). At the same time, it significantly improved sperm motility (P < 0.05) and also improved reproductive performance such as fertilization rate and hatching rate. To further reveal the mechanism underlying the effects of induced molting on semen quality and reproductive performance in aged Houdan roosters, we collected testes from 3 periods: 1 d before fasting (F0), 15 d after fasting (F15), and 32 d after recovery feeding (R32) for transcriptome sequencing analysis. A total of 5,671 genes were detected in F0, F15, and R32, and trend analysis of the 5,671 differential genes showed 2 significant trends (profile 5 and profile 2). KEGG enrichment analysis of the genes in the 2 profiles, revealed significantly enriched pathway regulation of actin cytoskeleton. In the regulation of actin cytoskeleton pathway, we found a protein kinase gene ( SRC ) and a senescence gene ( ROCK2 ). SRC was highly expressed at F15, leading to the phosphorylation of key substrates, which in turn disrupted the Sertoli cell spermatid connection and the spermiogenesis process, resulting in no mature spermatozoa produced from F15, SRC expression was inhibited at R32, the expression level was reduced, and mature spermatozoa reappeared. The senescence gene ROCK2 was highly expressed at F15 compared to F0 and R32, which may have been responsible for inducing senescence atrophy in the testes. [ABSTRACT FROM AUTHOR]

Aim of this study was to investigate the prevalence and genetic environment of the oxazolidinone resistance gene optrA in Streptococcus suis (S. suis) isolates from diseased pigs in China. A total of 178 S. suis isolates were screened for the optrA gene by PCR. The phenotypes and genotypes of optrA -positive isolates were investigated by antimicrobial susceptibility testing, core genome Multilocus Sequence Typing (cgMLST), capsular serotypes determination and whole-genome sequencing (WGS). Fifty-one (28.7%) S. suis isolates were positive for optrA. Phylogenetic analysis indicated that the spread of the optrA among S. suis isolates was primarily due to horizontal transfer. Analysis of S. suis serotypes from diseased pigs revealed substantial diversity. The genetic environment of optrA was complex and diverse and could be divided into 12 different types. Interestingly, we identified a novel integrative and conjugative element ICE Ssu 988S, carrying optrA and erm (T) genes. This is to the best of our knowledge the first report of the optrA and erm (T) co-located on an ICE in S. suis. Our results showed a high prevalence of optrA gene in S. suis isolates in China. Further research is needed to evaluate the importance of ICEs, as they horizontally propagate important clinical resistance genes. [ABSTRACT FROM AUTHOR]

HSPA8 (Heat shock 70 kDa protein 8) is a molecular chaperone involved in a variety of cellular processes. This gene may affect the proliferation, apoptosis and immune function of chicken macrophages, but the specific mechanism remains unclear. The purpose of this study was to explore the effect of the HSPA8 gene on the proliferation, apoptosis and immune function of chicken macrophages. In this study, a chicken HSPA8 overexpression plasmid, interference fragment and corresponding controls were transfected into HD11 cells, and then the expression of the HSPA8 gene, cell proliferation, cell cycle, apoptosis rate and immune function of each group were detected. The results showed that transfection of the HSPA8 overexpression plasmid significantly upregulated the level of HSPA8 expression in HD11 cells compared with the control; significantly promoted the proliferation of HD11 cells and the expression of PCNA , CCND1 and CCNB3 ; decreased the number of cells in the G1 phase and increased the number of cells in the S phase; decreased the rate of apoptosis and upregulated the expression of Bcl-2 ; and promoted the expression of the LPS-induced cytokines IL-1β , IL-6 and TNF-α. Transfection of the HSPA8 interference fragment significantly downregulated the level of HSPA8 expression in HD11 cells; significantly inhibited the proliferation of HD11 cells and the expression of PCNA , CCND1 and CDK1; increased the number of cells in the G1 phase and decreased the number of cells in the S phase; increased the rate of apoptosis, downregulated the expression of Bcl-2 and upregulated the expression levels of Fas and FasL ; and inhibited the expression of the LPS-induced cytokines IL-1β and NF-κB. The results suggested that HSPA8 promotes the proliferation of and inhibits the apoptosis of HD11 cells and has a proinflammatory effect. • HSPA8 can promote the proliferation of HD11 cells. • HSPA8 can inhibit the apoptosis of HD11 cells. • HSPA8 is involved in regulating the immune response of HD11 cells. • HSPA8 promotes inflammation by promoting the expression of LPS-induced inflammatory factors. [ABSTRACT FROM AUTHOR]

The elongation of very long chain fatty acids protein 6 (ELOVL6) encodes a fatty acid elongase that is responsible for the final step in endogenous saturated fatty acid synthesis and involves in de novo lipogenesis. Though the regulatory mechanism of ELOVL6 expression has been studied extensively, little is known about the role of miRNA in regulating ELOVL6 gene expression in chicken until now. To investigate the regulatory mechanism of miRNA on the expression of ELOVL6 gene, bioinformatics analysis was employed to predict the potential miRNAs that binding with the 3′untranslated region (3′UTR) of ELOVL6. The putative miRNA was further screened by comparative analysis with previous miRNA-seq results. Gga-miR-22-3p, which could bind with the 3′UTR of ELOVL6 and showed negative expression correlation with ELOVL6 gene in chicken liver, was obtained. Tissue expression profiles showed that gga-miR-22-3p and ELOVL6 are extensively expressed in many tissues, and ELOVL6 with high expression level in kidney and liver tissues, and gga-miR-22-3p with high expression in lung and heart. Dual-luciferase reporter assays results indicated that the expression of luciferase reporter gene linked with part sequence of the 3′UTR of chicken ELOVL6 gene was down-regulated by the overexpression of gga-miR-22-3p in the DF1 cells, and the down-regulation behavior was abolished when the gga-miR-22-3p binding site in 3′UTR of ELOVL6 was mutated ( P > 0.05). Furthermore, the ELOVL6 expression in chicken hepatocytes was down-regulated when miR-22-3p was over-expressed. Therefore, we concluded that miR-22-3p might involve in controlling the hepatic lipid composition through affecting the expression of ELOVL6 gene, and could serve as a regulator of lipid metabolism in the liver of egg-laying hen. [ABSTRACT FROM AUTHOR]

It has been recognized that colistin resistance is a growing problem that seriously impairs the clinical efficacy of colistin against bacterial infections. One strategy that has been proven to have therapeutic effect is to overcome the widespread emergence of antibiotic-resistant pathogens by combining existing antibiotics with promising non-antibiotic agents. In this work, antibiotic susceptibility testing, checkerboard assays and time-kill curves were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of the combination. The molecular mechanisms of tetrandrine in combination with colistin were analyzed using fluorometric assay and Real-time PCR. To predict possible interactions between tetrandrine and MCR-1, molecular docking assay was taken. Finally, we evaluated the in vivo efficacy of tetrandrine in combination with colistin against MCR-positive Salmonella. Overall, the combination of tetrandrine and colistin showed significant synergistic activity. In-depth mechanistic analysis showed that the combination of tetrandrine with colistin enhances the membrane-damaging ability of colistin, undermines the functions of proton motive force (PMF) and efflux pumps in MCR-positive bacteria. The results of molecular docking and RT-PCR analyses showed that tetrandrine not only affects the expression of mcr -1 but is also an effective MCR-1 inhibitor. Compared with colistin monotherapy, the combination of tetrandrine with colistin significantly reduced the bacterial load in vivo. Our findings demonstrated that tetrandrine serves as a potential colistin adjuvant against MCR-positive Salmonella. • In our study, the combination of tetrandrine and colistin drastically enhanced colistin bactericidal activity compared with monotreatment. • In-depth mechanistic analysis showed that tetrandrine potentiated colistin activity through enhancing the membrane-damaging ability of colistin. • Tetrandrine dramatically undermines the function of PMF and result in decreased intracellular ATP levels. In addition, the activity of efflux pump was significantly inhibited by the addition of tetrandrine in both single or combination treatments. • Tetrandrine not only affects the expression of mcr -1 but also as an effective MCR-1 inhibitor. • The discovery of tetrandrine as a potential adjuvant for colistin therapy in combination therapy for severe infections caused by MCR-1 positive Salmonella. [ABSTRACT FROM AUTHOR]