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1.
J Pharm Biomed Anal ; 249: 116370, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39047467

RESUMO

Brucellosis, a zoonotic disease caused by brucella infection, presents metabolic profile changes in patients that have not been extensively explored. This study utilized an ultra-high performance liquid chromatography tandem mass spectrometry based targeted metabolomic approach to comprehensively investigated metabolic changes in Brucella patients. Serum samples of brucellosis 50 patients and 50 well-matched healthy controls were analyzed for 228 metabolites, revealing significant alterations in 83 metabolites in brucellosis patients. Notably, disruptions were observed in key metabolite pathways, such as amino acid metabolism, urea cycle, tricarboxylic acid cycle (TCA), and fatty acid metabolism. Patients diagnosed with Brucellosis exhibited distinct differences in the levels of aspartate, glutamate, ß-alanine, and asparagine when compared to controls. Within the urea cycle, a significant downregulation of arginine was observed, whereas ornithine levels were considerably upregulated. In the TCA cycle, concentrations of 2-oxoglutarate, succinate, and malate were significantly elevated, while citrate levels demonstrated a notable decrease. Due to the interruption of the TCA cycle, glycolysis was accelerated to compensate for the resultant energy deficit in Brucella patients. Concurrently, there was a significant increase in the levels of short and medium-chain fatty acids, while long-chain fatty acids showed a marked decrease. The study systematically revealed significant metabolic alterations in Brucellosis patients and further explored the potential correlation between these changes and clinic symptoms, including fatigue, muscle soreness and prolonged fever. The results enhanced our understanding of Brucellosis, offering valuable insights potentially beneficial in formulating more effective treatment strategies and improving prognostic approaches.


Assuntos
Brucelose , Metabolômica , Espectrometria de Massas em Tandem , Humanos , Brucelose/metabolismo , Metabolômica/métodos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Estudos de Casos e Controles , Metaboloma , Ciclo do Ácido Cítrico , Adulto Jovem , Aminoácidos/metabolismo , Aminoácidos/sangue , Ácidos Graxos/metabolismo
2.
PLoS One ; 19(7): e0306429, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38980867

RESUMO

Brucella abortus (Ba) is a pathogen that survives inside macrophages. Despite being its preferential niche, Ba infects other cells, as shown by the multiple signs and symptoms humans present. This pathogen can evade our immune system. Ba displays a mechanism of down-modulating MHC-I on monocytes/macrophages in the presence of IFN-γ (when Th1 response is triggered) without altering the total expression of MHC-I. The retained MHC-I proteins are located within the Golgi Apparatus (GA). The RNA of Ba is one of the PAMPs that trigger this phenomenon. However, we acknowledged whether this event could be triggered in other cells relevant during Ba infection. Here, we demonstrate that Ba RNA reduced the surface expression of MHC-I induced by IFN-γ in the human bronchial epithelium (Calu-6), the human alveolar epithelium (A-549) and the endothelial microvasculature (HMEC) cell lines. In Calu-6 and HMEC cells, Ba RNA induces the retention of MHC-I in the GA. This phenomenon was not observed in A-549 cells. We then evaluated the effect of Ba RNA on the secretion of IL-8, IL-6 and MCP-1, key cytokines in Ba infection. Contrary to our expectations, HMEC, Calu-6 and A-549 cells treated with Ba RNA had higher IL-8 and IL-6 levels compared to untreated cells. In addition, we showed that Ba RNA down-modulates the MHC-I surface expression induced by IFN-γ on human monocytes/macrophages via the pathway of the Epidermal Growth Factor Receptor (EGFR). So, cells were stimulated with an EGFR ligand-blocking antibody (Cetuximab) and Ba RNA. Neutralization of the EGFR to some extent reversed the down-modulation of MHC-I mediated by Ba RNA in HMEC and A-549 cells. In conclusion, this is the first study exploring a central immune evasion strategy, such as the downregulation of MHC-I surface expression, beyond monocytes and could shed light on how it persists effectively within the host, enduring unseen and escaping CD8+ T cell surveillance.


Assuntos
Brucella abortus , Células Endoteliais , Células Epiteliais , Antígenos de Histocompatibilidade Classe I , Interferon gama , Humanos , Interferon gama/metabolismo , Interferon gama/farmacologia , Células Endoteliais/metabolismo , Células Endoteliais/microbiologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Células Epiteliais/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe I/genética , RNA Bacteriano/genética , Linhagem Celular , Regulação para Baixo/efeitos dos fármacos , Receptores ErbB/metabolismo , Brucelose/imunologia , Brucelose/metabolismo , Brucelose/microbiologia , Brucelose/genética , Complexo de Golgi/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos/microbiologia , Monócitos/metabolismo , Monócitos/imunologia , Monócitos/efeitos dos fármacos
3.
Cell Host Microbe ; 32(4): 588-605.e9, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38531364

RESUMO

Many powerful methods have been employed to elucidate the global transcriptomic, proteomic, or metabolic responses to pathogen-infected host cells. However, the host glycome responses to bacterial infection remain largely unexplored, and hence, our understanding of the molecular mechanisms by which bacterial pathogens manipulate the host glycome to favor infection remains incomplete. Here, we address this gap by performing a systematic analysis of the host glycome during infection by the bacterial pathogen Brucella spp. that cause brucellosis. We discover, surprisingly, that a Brucella effector protein (EP) Rhg1 induces global reprogramming of the host cell N-glycome by interacting with components of the oligosaccharide transferase complex that controls N-linked protein glycosylation, and Rhg1 regulates Brucella replication and tissue colonization in a mouse model of brucellosis, demonstrating that Brucella exploits the EP Rhg1 to reprogram the host N-glycome and promote bacterial intracellular parasitism, thereby providing a paradigm for bacterial control of host cell infection.


Assuntos
Brucella , Brucelose , Animais , Camundongos , Brucella/fisiologia , Proteômica , Brucelose/metabolismo , Retículo Endoplasmático/metabolismo
4.
Braz. j. infect. dis ; 13(4): 249-251, Aug. 2009. tab
Artigo em Inglês | LILACS | ID: lil-539757

RESUMO

Oxidative stress can be defined as an increase in oxidants and/or a decrease in antioxidant capacity. We aimed to determine total antioxidant capacity (TAC), total peroxide, malondialdehyde and catalase levels in plasma samples, and calculation of oxidative stress index (OSI) in patients with brucellosis to evaluate their oxidative status using a novel automated method. Sixty-nine patients with brucellosis and 69 healthy control subjects were included in the present study. Plasma levels of total peroxide and malondialdehyde were significantly increased in patients as compared with healthy controls (p<0.001 and p<0.001, respectively). In contrast, TAC level was significantly lower in patients as compared with controls (p<0.001). There was no statistically significant difference between the catalase results of the two groups (p>0.05). OSI level was significantly increased in patients as compared with healthy controls (p<0.001). In conclusion, oxidants were increased and antioxidants were decreased in patients with brucellosis. Oxidative stress was increased in patients with brucellosis.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Brucelose/metabolismo , Estresse Oxidativo/fisiologia , Antioxidantes/análise , Biomarcadores/sangue , Brucelose/sangue , Estudos de Casos e Controles , Catalase/sangue , Malondialdeído/sangue , Peróxidos/sangue
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