Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.097
Filtrar
1.
Biochem Biophys Res Commun ; 590: 152-157, 2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-34974304

RESUMO

Mycolic acids (MAs) are unique components of cell envelope of Mycobacterium or Corynebacterium and are key factors of their virulence to human. In order to develop new anti-Tuberculosis (TB) drugs, many efforts have paid on investigation of structures and functions of proteins involved in the biosynthesis pathway of MAs. FadD32 and polyketide synthase 13 (pks13) catalyze the last step of MAs synthesis. Here we present the crystal structures of FadD32 with substrates and holo-form of ACP-domain from Corynebacterium diphtheriae. The crystal structures and in vitro biochemical assays provide new insights into the assembly of FadD32 and pks13.

2.
Part Fibre Toxicol ; 19(1): 2, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34983566

RESUMO

BACKGROUND: Zinc oxide nanoparticles (ZnONPs) are widely used nanomaterial in personal cosmetics, such as skin creams and sunscreens, due to their whitening properties and strong UV light absorption. However, the safety issues and the hazards of ZnONPs, which can be taken up by the skin and cause skin toxicity, are still unclear. From a chemoprevention point of view, pterostilbene (PT) has been reported to prevent skin damage effectively by its anti-inflammatory and autophagy inducer effect. This study aims to determine the skin toxicity and the potential mechanisms of UVB and ZnONPs exposure and the preventive effect of PT. RESULTS: The co-exposure of UVB and ZnONPs elicit NLRP3 inflammasome activation and pyroptosis in keratinocytes. Furthermore, exposure to both UVB and ZnONPs also disrupts cellular autophagy, which increases cell exosome release. In vivo UVB and ZnONPs exposure triggers skin toxicity, as indicated by increased histological injury, skin thickness and transepidermal water loss. Notably, the NLRP3 inflammasome-mediated pyroptosis are also activated during exposure. Topical application of pterostilbene attenuates NLRP3 inflammasome activation and pyroptosis by decreasing ROS generation and mitochondrial ROS (mtROS) levels. In addition to its antioxidant effect, PT also reversed autophagy abnormalities by restoring normal autophagic flux and decreasing NLRP3 inflammasome-loaded exosome release. CONCLUSIONS: Our findings reveal that ZnONPs induce skin damage in conjunction with UVB exposure. This process involves an interplay of inflammasomes, pyroptosis, autophagy dysfunction, and exosomes in skin toxicity. PT alleviates skin inflammation by regulating the inflammasome-autophagy-exosome pathway, a finding which could prove valuable when further evaluating ZnONPs effects for cosmetic applications.

3.
Nat Commun ; 13(1): 269, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022412

RESUMO

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.


Assuntos
COVID-19/imunologia , SARS-CoV-2/fisiologia , Idoso , Autopsia , COVID-19/diagnóstico , COVID-19/genética , COVID-19/virologia , China , Diagnóstico , Feminino , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Humanos , Ativação Linfocitária , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Células Mieloides/imunologia , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , SARS-CoV-2/imunologia , Carga Viral
5.
Sci Total Environ ; 815: 152953, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34999076

RESUMO

Fe(III)-reducing bacteria (FRB) and Fe(II)-oxidizing bacteria (FOB) play essential roles in the biogeochemical cycling of iron (Fe). Although the redox transformation of Fe species mediated by FRB/FOB has been extensively studied, the co-responses of FRB and FOB and Fe species transformation in natural sediment under dynamic redox conditions are poorly known. This study explored the variations of potential FRB and FOB abundances and Fe species transformation in natural sediment during successive anoxic-oxic-anoxic-oxic-anoxic cycles. Compared with the pristine sediment sample, the FRB abundance increased 121-793% (initial: (2.6 ± 0.6) × 107 copies/g) in the anoxic stages, while it decreased by 38-64% in the oxic stages. The increase in FRB abundance was ascribed to energy gain of FRB from the reduction of the amorphous Fe(III) (Fe(III)am) and the crystalline Fe(III) (Fe(III)cry) to the aqueous Fe(II) (Fe(II)aq), the adsorbed Fe(II) (Fe(II)ad) and the amorphous Fe(II) (Fe(II)am), while the decrease was attributed to the oxidative stress caused by the reactive oxidant produced from the abiotic oxidation of Fe(II)aq, Fe(II)ad and Fe(II)am to Fe(III)am and Fe(III)cry. The FOB abundance decreased 38-44% (initial: (5 ± 1.8) × 107 copies/g) in the second and third anoxic stages, while slightly fluctuated in the oxic periods. This observation was contrary to the variation of FRB, which might be attributed to the strong resistance to oxidative stress of FOB and its ability to obtain energy under oxic conditions. Although the functions of FRB and FOB were impaired during anoxic-oxic cycles, the transformation of Fe(II)/Fe(III) was not immediately affected, which may be related to the residual reactivity of dead bacteria and the bio-availability of Fe(II)/Fe(III) species. In the anoxic-oxic alternation process, the iron cycle is mainly the mutual transformation between Fe(II)aq, Fe(II)ad, Fe(II)am and Fe(III)am, Fe(III)cry. This finding deepens our understanding of the biogeochemical cycling of Fe in the redox-dynamic environments.

6.
Diabetol Metab Syndr ; 14(1): 4, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991691

RESUMO

AIM: The association of polymorphisms in the three genes of SOCS3, JAK2 and STAT3 with genetic susceptibility to type 2 diabetes mellitus (T2DM) was explored, and its interaction with environmental factors such as hypertension and triglycerides was analyzed. METHODS: The Hardy-Weinberg balance test was used to analyze the random balance of genes in the population. The analysis of the association of SNPs with T2DM was performed using Pearson's chi-square test. Haplotype frequency distribution, SNPs-SNPs interaction and environmental factors were analyzed by chi-square test and logistic regression. RESULTS: The genotype distribution of SNPs rs2280148 of the SOCS3 gene was statistically significant. The allele frequency distribution of SNPs (rs4969168/rs2280148) was statistically different. After covariate correction, the SOCS3 gene locus (rs4969168) showed an association with T2DM in additive model, while the rs2280148 locus showed an association with T2DM in all three models. The locus (rs10974914/rs10815157) allele and genotype frequency distribution of JAK2 were statistically significant. After covariate correction, two SNPs in the gene showed association with T2DM in both additive and recessive models. The distribution of genotype frequencies of SNPs rs1053005 locus in gene STAT3 was statistically significant between the two groups. In recessive genetic models, rs1053005 locus polymorphisms was associated with T2DM. Haplotype S3 (G G)/S 4 (G T) of the SOCS3 gene as well as haplotype J2 (A G)/J 3 (G C) of the JAK2 gene were closely associated with T2DM. There was an interaction between SNPs rs4969168 and SNPs rs2280148 in the SOCS3 gene. There was an interaction between the SOCS3, JAK2 and STAT3 genes and hypertension/triglycerides. CONCLUSION: The SOCS3 and JAK2 genes may be associated with T2DM in the Chinese population, in which SNPs carrying the A allele (rs4969168)/G allele (rs2280148)/C allele (rs10815157) have a reduced risk of T2DM. Haplotype S3 (G G)/S 4 (G T) of the SOCS3 gene and haplotype J2 (A G)/J 3 (G C) of the JAK2 gene may be influencing factor for T2DM. The interaction between SNPs rs4969168 and SNPs rs2280148 increases the risk of T2DM. Hypertension and triglycerides may interact with SNPs of T2DM susceptibility genes.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35006484

RESUMO

PURPOSE: Higher levels of estrogen in obese patients may lead to incomplete inhibition by aromatase inhibitors (AIs). The aim of this study was to determine the impact of body mass index (BMI) on efficacy of AIs in patients with metastatic hormone receptor (HR)-positive breast cancer (BC). METHODS: We performed a retrospective chart review of all female patients with metastatic HR-positive BC on an AI in first- or second-line settings and seen at our academic institution between 2001 and 2020. The primary endpoint was progression-free survival (PFS), defined as the time from start of AI to disease progression or death from any cause. RESULTS: We identified 219 patients who had received an AI in the first- or second-line settings for metastatic HR-positive BC and with documented information on BMI. Of the 219 patients, 56% (123) had a low BMI (defined as < 27 kg/m2) and 44% (96) had a high BMI (≥ 27 kg/m2). The median PFS was 21.9 months (95% CI 14.5 to 28.4) in the low BMI group versus 20.2 months (95% CI 14.3 to 27.5) in the high BMI group (p = 0.73). CONCLUSION: While BMI influences efficacy of AIs in the adjuvant setting, our results suggest that in the metastatic setting, BMI may not impact the efficacy of AIs. This discrepancy could be due to other differences in disease characteristics that make complete aromatase inhibition more important in the adjuvant setting when disease burden is the lowest.

10.
Water Res ; 211: 118055, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35042072

RESUMO

Anaerobic membrane bioreactor (AnMBR) is a low-energy and promising solution for sewage treatment. During the treatment, the fouled membrane of AnMBR is recognized as an important barrier against pathogenic viruses. Here, the role of membrane fouling of an AnMBR at room temperature in the virus removal was investigated using MS2 bacteriophage as a virus surrogate. Results revealed that the virus removal efficiency of AnMBR was in the range of 0.2 to 3.6 logs, gradually increasing with the course of AnMBR operation. Virus removal efficiency was found to be significantly correlated with transmembrane pressure (R2=0.92, p<0.01), especially in the rapid fouling stage, indicating that membrane fouling was the key factor in the virus removal. The proportion of virus decreased from 52.03% to 15.04% in the membrane foulants when membrane fouling was aggravating rapidly, yet increased from 0.74% to 21.52% in the mixed liquor. Meanwhile, the permeate flux dramatically dropped. These imply that the primary rejection mechanism of virus by membrane in the slow fouling stage is the virus adsorption onto membrane, while the sieving effect is the main reason in the rapid fouling stage. Ex-situ virus rejection test unveiled that the cake layer was the main contributor to the overall virus rejection, while the greatest resistance-specific virus rejection was provided by the organic pore blocking. This paper provides operation strategies to balance enhanced virus removal and high permeate flux by regulating the membrane fouling process.

11.
J Hazard Mater ; 424(Pt B): 127423, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34649121

RESUMO

In this work, different Bi2S3 nanostructures were prepared from various single and dual sulfide precursors via a solvothermal method. It was found that Bi2S3 nanostructures prepared from dual sulfur precursors of L-cysteine and ammonium sulfide exhibited highest Cr(VI) removal ability with maximum Cr(VI) removal capacity of 148.95 mg/g in Cr(VI) solution (pH = 2). More importantly, the removal capacity strikingly increased to 223.33 and 240.25 mg/g in two kinds of actual industrial electroplating wastewater. By analyzing the components of actual electroplating wastewater and the results of control experiments in the absence and presence of different ions in Cr(VI) solution, it was found that SO42- played a critical role in the Cr(VI) removal over Bi2S3. The addition of SO42- could promote the conversion of Cr(VI) to Cr(III) on the surface of Bi2S3, thus leading to the enhanced Cr(VI) removal ability in actual electroplating wastewater. The Bi2S3 maintained its original Cr(VI) removal ability after four cycles in the electroplating wastewater, indicating the moderate reuse ability of the sample. This work not only demonstrated an highly efficient nanomaterials for the Cr(VI) removal in industrial electroplating wastewater, but also provided an insight on the influence of the components in wastewater on Cr(VI) removal.

12.
Sci Total Environ ; 803: 150126, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34525757

RESUMO

This work explored the feasibility of dewatered swine manure-derived biochar (DSMB) as an additive to facilitate anaerobic digestion (AD) of swine wastewater for energy recovery and antibiotic resistance genes (ARG) attenuation enhancements. With 20 g/L DSMB assistance, the methanogenic lag time of swine wastewater was shortened by 17.4-21.1%, and the maximum CH4 production rate increased from 40.8 mL/d to 48.3-50.5 mL/d, among which DSMB prepared under 300 °C exhibited a better performance than that prepared under 500 °C and 700 °C. Integrated analysis of DSMB electrochemical properties, microbial electron transfer system activity, and microbial community succession revealed the potential of DSMB-300 to act as redox-active electron transfer mediators between syntrophic microbes to accelerate syntrophic methanogenesis via potential direct interspecies electron transfer. Meanwhile, DSMB preparation by pyrolysis dramatically reduced ARG abundance by almost 4 logs. Adding DSMB into AD not only strengthened the attenuation efficiency of ARG in the original swine wastewater, but also effectively controlled the potential risk of horizontal gene transfer by mitigating 74.8% of the mobile gene elements abundance. Accordingly, we proposed a win-win scenario for bio-waste management in swine farms, highlighting the more advanced energy recovery and ARG attenuation compared to the current status.


Assuntos
Esterco , Águas Residuárias , Anaerobiose , Animais , Antibacterianos/farmacologia , Carvão Vegetal , Resistência Microbiana a Medicamentos/genética , Suínos
13.
Biomed Pharmacother ; 145: 112384, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34915672

RESUMO

Aquaporin-4 (AQP-4) is an aquaporin composed of six helical transmembrane domains and two highly conserved ASN-pro-ALA (NPA) motifs. It is strongly expressed in rodent and human spinal cord tissues and plays a key role in the pathological process after SCI. After SCI, edema, glial scarring, and inflammation can accelerate the progression of injury and lead to deterioration of function. Many studies have reported that AQP-4 plays an important role in SCI. In particular, it plays an important role in secondary pathological processes (spinal cord edema, glial scar formation, and inflammatory response) after SCI. Loss of AQP-4 has been associated with reduced spinal edema and improved prognosis after SCI in mice. In addition, downregulation of AQP-4 reduces glial scar formation and the inflammatory response after SCI. There is a consensus from numerous studies that AQP-4 may be a potential target for SCI therapy, which guides the ongoing investigation for molecular therapy of SCI. Here, we review the structure of AQP-4, its expression in normal and damaged spinal cord, and its role in SCI, as well as discuss the theoretical basis for the treatment of SCI.

14.
Cancer Lett ; 525: 179-197, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-34752845

RESUMO

The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitous cation channel possessing kinase activity. TRPM7 mediates a variety of physiological responses by conducting flow of cations such as Ca2+, Mg2+, and Zn2+. Here, we show that the activation of TRPM7 channel stimulated by chemical agonists of TRPM7, Clozapine or Naltriben, inhibited autophagy via mediating Zn2+ release to the cytosol, presumably from the intracellular Zn2+-accumulating vesicles where TRPM7 localizes. Zn2+ release following the activation of TRPM7 disrupted the fusion between autophagosomes and lysosomes by disturbing the interaction between Sxt17 and VAMP8 which determines fusion status of autophagosomes and lysosomes. Ultimately, the disrupted fusion resulting from stimulation of TRPM7 channels arrested autophagy. Functionally, we demonstrate that the autophagy inhibition mediated by TRPM7 triggered cell death and suppressed metastasis of cancer cells in vitro, more importantly, restricted tumor growth and metastasis in vivo, by evoking apoptosis, cell cycle arrest, and reactive oxygen species (ROS) elevation. These findings represent a strategy for stimulating TRPM7 to combat cancer.


Assuntos
Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Proteínas R-SNARE/genética , Canais de Cátion TRPM/genética , Apoptose/efeitos dos fármacos , Autofagossomos/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Clozapina/farmacologia , Humanos , Lisossomos/efeitos dos fármacos , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Metástase Neoplásica , Neoplasias/genética , Transdução de Sinais/efeitos dos fármacos , Canais de Cátion TRPM/agonistas , Zinco/farmacologia
16.
3 Biotech ; 11(12): 493, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34881156

RESUMO

With the increasing growth of the herbal market, a rapid and easy-to-use system is highly desirable in the high-throughput identification of massive herbal medicine samples. Here, an ultrafast and colorimetric detection system was devised based on simplifying template preparation and a newly developed amplification technique, named colorimetric direct-VPCR. The system was successfully applied to the identification of Pinelliae Rhizoma. Compared to the traditional method, the whole test can be finished within 30 min from the sample treatment to the testing results. The method was evaluated by correctly identifying 72 samples obtained from 9 different habitats, demonstrating its high reliability. In summary, we present an ultrafast (less than 30 min) and colorimetric detection platform (under ultraviolet lamp) based on direct-VPCR for the identification of Pinelliae Rhizoma. The high practicability (100% accuracy) of this pipeline enables it to be a promising method in the routine detection of other herbal materials. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-021-03035-9.

17.
Food Res Int ; 150(Pt A): 110768, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34865783

RESUMO

Vinegar is consumed worldwide as a food condiment, especially in the Chinese diet. The present study optimized the addition of A. niger biofortified-bran Qu (0.3%, 0.45%, and 0.6%) as additional starter to improve total acid content and starch utilization rate in industrial-scale Baoning vinegar production. In addition, this novel study determined the quality and microbial community changes of Baoning vinegar during three-round biofortification in industrial scale. Our results indicated that A. niger biofortified-bran Qu added at 0.6% resulted in higher total acid content and starch utilization rate of vinegar Pei. Biofortification imposed minor changes in the microbial community during three-round biofortification, and more variation was observed in fungal community than that in bacterial community. Most importantly, the quality of Baoning vinegar remained relatively stable. This information further confirmed the feasibility of multiple rounds of A. niger biofortification, and can be used to provide theoretical basis for industrial-scale production.

18.
Front Mol Biosci ; 8: 751938, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869587

RESUMO

Krüppel-like factor 10 (KLF10) is a phospho-regulated transcriptional factor involved in many biological processes including lipogenesis; however, the transcriptional regulation on lipogenesis by KLF10 remains largely unclear. Lipogenesis is important in the development of nonalcoholic fatty liver disease (NAFLD) which was known regulated mainly by AMP-activated protein kinase (AMPK) and sterol regulatory element-binding protein (SREBP-1C). Interesting, our previous study using phosphorylated site prediction suggested a regulation of AMPK on KLF10. Therefore, we aimed to study the protein-protein interactions of AMPK on the regulation of KLF10, and to delineate the mechanisms of phosphorylated KLF10 in the regulation of NAFLD through SREBP-1C. We performed in vitro and in vivo assays that identified AMPK phosphorylates KLF10 at Thr189 and subsequently modulates the steady state level of KLF10. Meanwhile, a chromatin immunoprecipitation-chip assay revealed the novel target genes and signaling cascades of corresponding to phosphorylated KLF10. SREBP-1C was identified as a target gene suppressed by phosphorylated KLF10 through promoter binding. We further performed high-fat-diet-induced NAFLD models using hepatic-specific KLF10 knockout mice and wild-type mice and revealed that KLF10 knockout markedly led to more severe NAFLD than that in wild-type mice. Taken together, our findings revealed for the first time that AMPK activates and stabilizes the KLF10 protein via phosphorylation at Thr189, thereby repressing the expression of SREBP-1C and subsequent lipogenesis pathways along with metabolic disorders. We suggested that the targeted manipulation of liver metabolism, particularly through increased KLF10 expression, is a potential alternative solution for treating NAFLD.

19.
Orthop Surg ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34870370

RESUMO

OBJECTIVE: To investigate the effect of platelet-rich plasma on tendon-bone healing after anterior cruciate ligament reconstruction. METHODS: This retrospective study included 85 patients (range, 18-50 years; mean age, 33.95 ± 10.53 years; male/female, 49/36) who underwent anterior cruciate ligament reconstruction using autologous hamstring tendons between August 2017 and June 2019 at our institute. The participants in the study group (n = 42) were injected with platelet-rich plasma at both ends of the tendon graft, while those in the control group (n = 43) received an injection of normal saline. Magnetic resonance imaging signal/noise quotient values of the femoral and tibial ends, knee Lysholm scores, and International Knee Documentation Committee scores were compared at 3, 6, and 12 months postoperatively. RESULTS: The signal/noise quotient values of the femoral and tibial ends in both groups were higher at 6 months than at 3 and 12 months postoperatively. The signal/noise quotient values of the tibial end were significantly lower in the platelet-rich plasma group than in the normal saline group at all follow-up time points (P < 0.05). The signal/noise quotient values of the tibial and femoral ends in both groups were significantly different at 3, 6, and 12 months postoperatively (P < 0.05). Additionally, the signal/noise quotient values of the tibia were significantly lower than those of the femur in both groups (P < 0.05). The Lysholm and International Knee Documentation Committee scores were significantly better in the platelet-rich plasma group than in the normal saline group only at 3 months postoperatively. No complications, such as knee joint infection or vascular and nerve injuries, occurred in any of the 85 patients. The knee flexion of all patients were more than 90°, and the straight degree was 0°. No joint stiffness was observed in all patients. CONCLUSION: Platelet-rich plasma can promote tendon-bone healing in grafts and can improve early postoperative knee joint function.

20.
Microbiol Spectr ; : e0114121, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851156

RESUMO

The emergence of high-level tigecycline resistance mediated by plasmid-borne tet(X) genes greatly threatens the clinical effectiveness of tigecycline. However, the dissemination pattern of plasmid-borne tet(X) genes remains unclear. We here recovered tet(X)-positive Acinetobacter isolates from 684 fecal and environmental samples collected at six livestock farms. Fifteen tet(X)-positive Acinetobacter isolates were identified, mainly including 9 tet(X3)- and 5 tet(X6)-positive Acinetobacter towneri isolates. A clonal dissemination of tet(X3)-positive A. towneri was detected in a swine farm, while the tet(X6)-positive A. towneri isolates mainly disseminated sporadically in the same farm. A tet(X3)-carrying plasmid (pAT181) was self-transmissible from a tigecycline-susceptible A. towneri strain to Acinetobacter baumannii strain ATCC 17978, causing 64- to 512-fold increases in the MIC values of tetracyclines (including tigecycline). Worrisomely, pAT181 was stably maintained and increased the growth rate of strain ATCC 17978. Further identification of tet(X) genes in 10,680 Acinetobacter genomes retrieved from GenBank revealed that tet(X3) (n = 249), tet(X5)-like (n = 61), and tet(X6) (n = 53) were the prevalent alleles mainly carried by four species, and most of them were livestock associated. Phylogenetic analysis showed that most of the tet(X3)- and tet(X6)-positive isolates disseminated sporadically. The structures of the tet(X3), and tet(X6) plasmidomes were highly diverse, and no epidemic plasmids were detected. However, cross-species and cross-region transmissions of tet(X3) might have been mediated by several plasmids in a small proportion of strains. Our study implies that horizontal plasmid transfer may be insignificant for the current dissemination of tet(X3) and tet(X6) in Acinetobacter strains. Continuous surveillance for tet(X) genes in the context of One Health is necessary to prevent them from transmitting to humans. IMPORTANCE Recently identified plasmid-borne tet(X) genes have greatly challenged the efficiency of tigecycline, a last-resort antibiotic for severe infection, while the dissemination pattern of the plasmid-borne tet(X) genes remains unclear. In this study, we identified a clonal dissemination of tet(X3)-positive A. towneri isolates on a swine farm, while the tet(X6)-positive A. towneri strains mainly disseminated sporadically on the same farm. Of more concern, a tet(X3)-carrying plasmid was found to be self-transmissible, resulting in enhanced tigecycline resistance and growth rate of the recipient. Further exploration of a global data set of tet(X)-positive Acinetobacter genomes retrieved from GenBank revealed that most of the tet(X3)- and tet(X6)-positive isolates shared a highly distant relationship, and the structures of tet(X3) and tet(X6) plasmidomes exhibited high mosaicism. Notably, some of the isolates belong to Acinetobacter species that are opportunistic pathogens and have been identified as sources of nosocomial infections, raising concerns about transmission to humans in the future. Our study evidenced the sporadic dissemination of tet(X3) and tet(X6) in Acinetobacter strains and the necessity of continuous surveillance for tet(X) genes in the context of One Health.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...