RESUMEN
BACKGROUND: Drought is one of the main environmental factors limiting plant growth and development. Pennisetum purpureum Schum. was used to explore the mitigation effects of exogenous strigolactone (SL) on drought stress during the seedling stage. The effects of different concentrations (1, 3, 5, and 7 µmol·L- 1) of SL on the photosynthesis characteristics, growth performance, and endogenous abscisic acid (ABA) of P. purpureum under drought stress were studied. RESULTS: Exogenous SL could effectively alleviate the inhibitory effect of drought stress on P. purpureum growth. Compared with drought stress, the net photosynthesis rate, stomatal conductance, transpiration rate, and water-use efficiency of the leaves of P. purpureum after SL treatment significantly increased, thereby exerting a significant mitigation effect on the decrease in photosystem II maximum photochemical efficiency and the performance index based on light absorption caused by drought. Moreover, the exogenous application of SL can effectively increase the fresh and dry weight of the leaves and roots and the main-root length. After applying SL for 120 h, the ABA content of P. purpureum decreased significantly. The activity of key enzymes of photosynthesis significantly increased after 48 h of external application of SL to P. purpureum. CONCLUSIONS: SL treatment can improve the photosynthesis performance of P. purpureum leaves under drought conditions and increase the antioxidant capacity of the leaves, thereby reducing the adverse effects of drought, promoting the growth of P. purpureum, and effectively improving the drought resistance of P. purpureum.
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Cenchrus , Plantones , Plantones/fisiología , Estrés Fisiológico , Sequías , Ácido Abscísico/farmacología , Fotosíntesis , Hojas de la Planta/fisiologíaRESUMEN
Complement receptor 3 (CD11b/CD18) is an important receptor that mediates adhesion, phagocytosis and chemotaxis in various immunocytes. The conidia of the medically-important pathogenic fungus, Aspergillus fumigatus can be internalized into alveolar epithelial cells to disseminate its infection in immunocompromised host; however, the role of CR3 in this process is poorly understood. In the present study, we investigated the potential role of CR3 on A. fumigatus internalization into type II alveolar epithelial cells and its effect on host intracellular PA content induced by A. fumigatus. We found that CR3 is expressed in alveolar epithelial cells and that human serum and bronchoalveolar lavage fluid (BALF) could improve A. fumigatus conidial internalization into A549 type II alveolar epithelial cell line and mouse primary alveolar epithelial cells, which were significantly inhibited by the complement C3 quencher and CD11b-blocking antibody. Serum-opsonization of swollen conidia, but not resting conidia led to the increase of cellular phosphatidic acid (PA) in A549 cells during infection. Moreover, both conidial internalization and induced PA production were interfered by CD11b-blocking antibody and dependent on FAK activity, but not Syk in alveolar epithelial cells. Overall, our results revealed that CR3 is a critical modulator of Aspergillus fumigatus internalization into alveolar epithelial cells.
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Células Epiteliales Alveolares , Aspergillus fumigatus , Antígeno CD11b/inmunología , Quinasa 1 de Adhesión Focal/inmunología , Ácidos Fosfatidicos/química , Células A549 , Células Epiteliales Alveolares/inmunología , Células Epiteliales Alveolares/microbiología , Animales , Aspergilosis/inmunología , Antígenos CD18 , Humanos , Ratones , Opsonización , Esporas FúngicasRESUMEN
Invasive pulmonary aspergillosis induced by the pathogenic fungus Aspergillus fumigatus is one of the common fatal complications in immunocompromised patients. Lung epithelial cells play an important role in host immune defense against A. fumigatus. However, the interaction between lung epithelial cells and A. fumigatus conidia is not fully understood. In this study, we used the swollen conidia of A. fumigatus to stimulate the type II lung epithelial A549 cells. Results showed that swollen conidia could significantly increase RNA transcription and protein expression of interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1), but not TNF-α in A549 cells in a time-dependent manner. Moreover, serum opsonization was able to improve the release of inflammatory factors induced by swollen conidia. Blocking of the dectin-1 or CR3 receptors, or both simultaneously, in the A549 cells could decrease the release of IL-8 and MCP-1. Additionally, blocking dectin-1 or CR3 could inhibit the transcription of nuclear factor NF-κB that was activated by swollen conidia. Here we reported for the first time that dectin-1 and CR3 receptors in A549 cells mediate the release of pro-inflammatory factors IL-8 and MCP-1 induced by A. fumigatus.
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Aspergillus fumigatus , Interleucina-8 , Células Epiteliales Alveolares , Quimiocina CCL2 , Células Epiteliales , Humanos , Interleucina-8/genética , Lectinas Tipo C , Antígeno de Macrófago-1 , Esporas FúngicasRESUMEN
Aspergillus fumigatus is able to internalize into lung epithelial cells to escape from immune attack for further dissemination. We previously reported that gliotoxin, a major mycotoxin of A. fumigatus, promotes this internalization; however, the mechanism remained unclear. Here, we report that gliotoxin is able to induce cofilin phosphorylation in A549 type II human pneumocytes. Either too high or too low a level of cofilin phosphorylation blocked the gliotoxin-induced actin cytoskeleton rearrangement and A. fumigatus internalization. LIM domain kinase 1 (LIMK1) and its upstream small GTPases (Cdc42 and RhoA, but not Rac1) predominantly mediated the gliotoxin-induced cofilin phosphorylation and A. fumigatus internalization. Simultaneously, gliotoxin significantly stimulated an increase in cAMP; however, adding an antagonist of PKA did not block gliotoxin-induced A. fumigatus internalization. In vivo, exogenous gliotoxin helped gliotoxin synthesis deficient strain gliPΔ invade into the lung tissue and the lung fungal burden increased markedly in immunosuppressed mice. In conclusion, these data revealed a novel role of gliotoxin in inducing cofilin phosphorylation mostly through the Cdc42/RhoA-LIMK1 signaling pathway to promote actin cytoskeleton rearrangement and internalization of A. fumigatus into type II human pneumocytes.
RESUMEN
Aspergillus fumigatus causes most of aspergillosis in clinic and comprehensive function analysis of its key protein would promote anti-aspergillosis. In a previous study, we speculated actin depolymerizing factor cofilin might be essential for A. fumigatus viability and found its overexpression upregulated oxidative response and cell wall polysaccharide synthesis of this pathogen. Here, we constructed a conditional cofilin mutant to determine the essential role of cofilin. And the role of cofilin downregulation and phosphorylation in A. fumigatus was further analyzed. Cofilin was required for the polarized growth and heat sensitivity of A. fumigatus. Downregulation of cofilin caused hyphal cytoplasmic leakage, increased the sensitivity of A. fumigatus to sodium dodecyl sulfonate but not to calcofluor white and Congo Red and farnesol, and enhanced the basal phosphorylation level of MpkA, suggesting that cofilin affected the cell wall integrity (CWI) signaling. Downregulation of cofilin also increased the sensitivity of A. fumigatus to alkaline pH and H2O2. Repressing cofilin expression in A. fumigatus lead to attenuated virulence, which manifested as lower adherence and internalization rates, weaker host inflammatory response and shorter survival rate in a Galleria mellonella model. Expression of non-phosphorylated cofilin with a mutation of S5A had little impacts on A. fumigatus, whereas expression of a mimic-phosphorylated cofilin with a mutation of S5E resulted in inhibited growth, increased phospho-MpkA level, and decreased pathogenicity. In conclusion, cofilin is crucial to modulating the polarized growth, stress response, CWI and virulence of A. fumigatus.
RESUMEN
BACKGROUND: Carbapenem resistance in Acinetobacter baumannii in China was mainly mediated by OXA-23-like carbapenemases, while OXA-24/40-like carbapenemases were rarely identified. OXA-72 is one variant of OXA-24/40-like carbapenemases. This study aimed to demonstrate the epidemiology and characterizations of OXA-72-producing A. baumannii in a Chinese hospital. METHODS: A total of 107 clinical A. calcoaceticus-A. baumannii (Acb) complex isolates were collected in a Chinese hospital during between 2014 and 2016. These isolates were identified using Vitek 2 system and gyrB multiplex PCR. Vitek 2 system was used for antibiotic susceptibility testing. Genes encoding for major classes of carbapenemases were investigated by PCR. Rep-PCR was used for genotyping of all the A. baumannii isolates. The risk factors for carriage of OXA-72-producing or OXA-23-producing A. baumannii were analyzed through univariate and multivariate logistic regression. RESULTS: Of the 107 Acb isolates collected, 101 isolates (94.4%) and 6 isolates (5.6%) were identified as A. baumannii and A. pittii, respectively. 78 A. baumannii isolates (77.2%) were carbapenem resistant and mainly cultured from intensive care unit (ICU). blaOXA-72 and blaOXA-23 genes were identified in 45(57.7%) and 33(42.3%) carbapenem-resistant A. baumannii (CRAB), respectively. Multivariate risk factor analyses showed that prior carbapenem usage and nasogastric intubation were significantly associated with carriage of OXA-72-producing A. baumannii or OXA-23-producing A. baumannii. Rep-PCR analysis showed that 9 and 22 Rep-PCR types were assigned to 78 CRAB isolates and 23 carbapenem-susceptible A. baumannii (CSAB) isolates, respectively. A higher diverstiy of Rep-PCR patterns was observed among OXA-72-producing A. baumannii isolates than OXA-23-producing A. baumannii isolates, but all of them belonged to the same clone complex. MLST analysis suggested that the OXA-72 isolates from this study correspond to CC92/CC2 clone complex. CONCLUSIONS: This study demonstrates high prevalence and potential clonal spread of closely related genotypes of OXA-72-producing A. baumannii within a Chinese hospital. Continuous surveillance is necessary to monitor the dissemination of these strains in other healthcare settings to guide infection control policies in order to curb the spread of this bacterium.
Asunto(s)
Infecciones por Acinetobacter/diagnóstico , Acinetobacter baumannii/metabolismo , Proteínas Bacterianas/genética , beta-Lactamasas/genética , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/epidemiología , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas Bacterianas/metabolismo , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , China/epidemiología , Estudios Transversales , Farmacorresistencia Bacteriana/genética , Femenino , Humanos , Unidades de Cuidados Intensivos , Modelos Logísticos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Prevalencia , Adulto Joven , beta-Lactamasas/metabolismoRESUMEN
Aspergillus fumigatus is a major pathogen of invasive pulmonary aspergillosis. The small GTPase, Rho1, of A. fumigatus is reported to comprise a potential regulatory subunit of ß-1,3-glucan synthase and is indispensable for fungal viability; however, the role of AfRho1 on the growth, cell wall integrity, and pathogenesis of A. fumigatus is still poorly understood. We constructed A. fumigatus mutants with conditional- and overexpression of Rho1 and found that defects of AfRho1 expression led to the reduction of ß-1,3-glucan and glucosamine moieties on the cell wall, with down-regulated transcription of genes in the cell wall integrity signaling pathway and a decrease of calcofluor white (CFW)-stimulated mitogen-activated protein kinase (MpkA) phosphorylation and cytoplasmic leakage compared to those of the wild-type strain (WT). In addition, down-regulation of AfRho1 expression caused much higher sensitivity of A. fumigatus to H2O2 and alkaline pH compared to that of WT. Decrease of AfRho1 expression also attenuated the A. fumigatus pathogenicity in Galleria mellonella and inhibited conidial internalization into lung epithelial cells and inflammatory factor release. In contrast, overexpression of Rho1 did not alter A. fumigatus morphology, susceptibility to cell wall stresses, or pathogenicity relative to its parental strain. Taken together, our findings support AfRho1 as an essential regulator of the cell wall integrity, stress response, and pathogenesis of A. fumigatus.
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Aspergillus fumigatus/enzimología , Pared Celular/fisiología , Proteínas Fúngicas/fisiología , Proteínas de Unión al GTP rho/fisiología , Células A549 , Animales , Aspergilosis/microbiología , Aspergillus fumigatus/patogenicidad , Aspergillus fumigatus/fisiología , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Mariposas Nocturnas/microbiología , Estrés Fisiológico , Virulencia/genéticaRESUMEN
The destruction of pulmonary epithelium is a major feature of lung diseases caused by the fungal pathogen Aspergillus fumigatus (A. fumigatus). Gliotoxin, a major mycotoxin of A. fumigatus, is widely postulated to be associated with the tissue invasion. However, the mechanism is unclear. In this study, we first discovered that cofilin, a regulator of actin dynamics in the pulmonary epithelial cells, existed mainly in the form of oligomer, which kept it unable to depolymerize actin filaments. Gliotoxin could reduce the formation of cofilin oligomer and promote the release of active cofilin monomer by regulating cofilin phosphorylation balance. Then, the active cofilin induced the dissolution of actin stress fibers to result in the disruption of pulmonary epithelium barrier function. Collectively, our study revealed a novel mechanism of gliotoxin destructing lung epithelium barrier function and for the first time indicated the role of cofilin oligomer in this process.
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Factores Despolimerizantes de la Actina/metabolismo , Actinas/metabolismo , Células Epiteliales/efectos de los fármacos , Gliotoxina/toxicidad , Pulmón/efectos de los fármacos , Fibras de Estrés/metabolismo , Células A549/efectos de los fármacos , Animales , Aspergillus fumigatus/patogenicidad , Línea Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Humanos , Pulmón/patología , Ratones , Ratones Endogámicos C57BL , Fosforilación , SolubilidadRESUMEN
The use of azole fungicides in agriculture is believed to be one of the main reasons for the emergence of azole resistance in Aspergillus fumigatus Though widely used in agriculture, imidazole fungicides have not been linked to resistance in A. fumigatus This study showed that elevated MIC values of imidazole drugs were observed against A. fumigatus isolates with TR34/L98H/S297T/F495I mutation, but not among isolates with TR34/L98H mutation. Short-tandem-repeat (STR) typing analysis of 580 A. fumigatus isolates from 20 countries suggested that the majority of TR34/L98H/S297T/F495I strains from China were genetically different from the predominant major clade comprising most of the azole-resistant strains and the strains with the same mutation from the Netherlands and Denmark. Alignments of sterol 14α-demethylase sequences suggested that F495I in A. fumigatus was orthologous to F506I in Penicillium digitatum and F489L in Pyrenophora teres, which have been reported to be associated with imidazole resistance. In vitro antifungal susceptibility testing of different recombinants with cyp51A mutations further confirmed the association of the F495I mutation with imidazole resistance. In conclusion, this study suggested that environmental use of imidazole fungicides might confer selection pressure for the emergence of azole resistance in A. fumigatus.
Asunto(s)
Antifúngicos/farmacología , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/genética , Sistema Enzimático del Citocromo P-450/genética , Farmacorresistencia Fúngica/genética , Proteínas Fúngicas/genética , Imidazoles/farmacología , Esterol 14-Desmetilasa/genética , Agricultura/métodos , Secuencia de Aminoácidos , Aspergilosis/tratamiento farmacológico , Aspergillus fumigatus/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Selección Genética/genética , Alineación de SecuenciaRESUMEN
Through some specific amino acid residues, cofilin, a ubiquitous actin depolymerization factor, can significantly affect mitochondrial function related to drug resistance and apoptosis in Saccharomyces cerevisiae; however, this modulation in a major fungal pathogen, Aspergillus fumigatus, was still unclear. Hereby, it was found, first, that mutations on several charged residues in cofilin to alanine, D19A-R21A, E48A, and K36A, increased the formation of reactive oxygen species and induced apoptosis along with typical hallmarks, including mitochondrial membrane potential depolarization, cytochrome c release, upregulation of metacaspases, and DNA cleavage, in A. fumigatus Two of these mutations (D19A-R21A and K36A) increased acetyl coenzyme A and ATP concentrations by triggering fatty acid ß-oxidation. The upregulated acetyl coenzyme A affected the ergosterol biosynthetic pathway, leading to overexpression of cyp51A and -B, while excess ATP fueled ATP-binding cassette transporters. Besides, both of these mutations reduced the susceptibility of A. fumigatus to azole drugs and enhanced the virulence of A. fumigatus in a Galleria mellonella infection model. Taken together, novel and key charged residues in cofilin were identified to be essential modules regulating the mitochondrial function involved in azole susceptibility, apoptosis, and virulence of A. fumigatus.
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Factores Despolimerizantes de la Actina/genética , Antifúngicos/farmacología , Apoptosis/genética , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/genética , Azoles/farmacología , Farmacorresistencia Fúngica/genética , Mitocondrias/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Acetilcoenzima A/biosíntesis , Aspergillus fumigatus/patogenicidad , Sistema Enzimático del Citocromo P-450/biosíntesis , Ergosterol/biosíntesis , Proteínas Fúngicas/biosíntesis , Humanos , Virulencia/genéticaRESUMEN
Aspergillus fumigatus is a major fungal pathogen that is responsible for approximately 90% of human aspergillosis. Cofilin is an actin depolymerizing factor that plays crucial roles in multiple cellular functions in many organisms. However, the functions of cofilin in A. fumigatus are still unknown. In this study, we constructed an A. fumigatus strain overexpressing cofilin (cofilin OE). The cofilin OE strain displayed a slightly different growth phenotype, significantly increased resistance against H2O2 and diamide, and increased activation of the high osmolarity glycerol pathway compared to the wild-type strain (WT). The cofilin OE strain internalized more efficiently into lung epithelial A549 cells, and induced increased transcription of inflammatory factors (MCP-1, TNF-α and IL-8) compared to WT. Cofilin overexpression also resulted in increased polysaccharides including ß-1, 3-glucan and chitin, and increased transcription of genes related to oxidative stress responses and polysaccharide synthesis in A. fumigatus. However, the cofilin OE strain exhibited similar virulence to the wild-type strain in murine and Galleria mellonella infection models. These results demonstrated for the first time that cofilin, a regulator of actin cytoskeleton dynamics, might play a critical role in the regulation of oxidative stress responses and cell wall polysaccharide synthesis in A. fumigatus.
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Factores Despolimerizantes de la Actina/fisiología , Actinas/metabolismo , Aspergillus fumigatus/metabolismo , Estrés Oxidativo , Células A549 , Factores Despolimerizantes de la Actina/genética , Factores Despolimerizantes de la Actina/metabolismo , Aspergillus fumigatus/crecimiento & desarrollo , Aspergillus fumigatus/patogenicidad , Western Blotting , Pared Celular/metabolismo , Endocitosis , Humanos , Peróxido de Hidrógeno/metabolismo , Mediadores de Inflamación/metabolismo , Interleucina-8/genética , Proteínas Quimioatrayentes de Monocitos/genética , Polimerizacion , Polisacáridos/biosíntesis , Polisacáridos/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Transcripción Genética , Factor de Necrosis Tumoral alfa/genética , VirulenciaRESUMEN
Although belonging to one of the most common type of nosocomial infection, there was currently no simple prediction model for lower respiratory tract infections (LRTIs). This study aims to develop a risk index based system for predicting nosocomial LRTIs based on data from a large point-prevalence survey. Among the 49328 patients included, the prevalence of nosocomial LRTIs was 1.70% (95% confidence interval [CI], 1.64% to 1.76%). The areas under the receiver operating characteristic (ROC) curve for logistic regression and fisher discriminant analysis were 0.907 (95% CI, 0.897 to 0.917) and 0.902 (95% CI, 0.892 to 0.912), respectively. The constructed risk index based system also displayed excellent discrimination (area under the ROC curve: 0.905 [95% CI, 0.895 to 0.915]) to identify LRTI in internal validation. Six risk levels were generated according to the risk score distribution of study population, ranging from 0 to 5, the corresponding prevalence of nosocomial LRTIs were 0.00%, 0.39%, 3.86%, 12.38%, 28.79% and 44.83%, respectively. The sensitivity and specificity of prediction were 0.87 and 0.79, respectively, when the best cut-off point of risk score was set to 14. Our study suggested that this newly constructed risk index based system might be applied to boost more rational infection control programs in clinical settings.
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Infección Hospitalaria/diagnóstico , Infección Hospitalaria/epidemiología , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Análisis Discriminante , Humanos , Modelos Logísticos , Prevalencia , Curva ROC , Factores de RiesgoRESUMEN
AIM: To assess the effectiveness of antibiotic therapy against five indicator bacteria in a Chinese hospital using an index-based approach. METHODS: The study population comprises 1031 patients who had one clinically significant bacterial isolate in 2008, 2010 and 2013. Drug resistance index (DRI) based on pathogens was calculated. RESULTS: The adaptive DRIs for Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus decreased, while both adaptive and fixed DRIs for Acinetobacter spp. increased from 2008 to 2013. The adaptive DRIs for Escherichia coli increased from 2008 to 2013, while the fixed DRIs exhibited a decreasing trend. CONCLUSION: DRI could be used to demonstrate the changes of antimicrobial resistance and prescribing over time as a result of evolutionary processes and governmental regulatory interference.
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Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Hospitales , Acinetobacter/efectos de los fármacos , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Bacterias/patogenicidad , Beijing , Infección Hospitalaria/tratamiento farmacológico , Farmacorresistencia Bacteriana/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Humanos , Control de Infecciones , Klebsiella pneumoniae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Medicamentos bajo Prescripción , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacosRESUMEN
Azole resistance in Aspergillus fumigatus has emerged as a worldwide public health problem. We sought here to demonstrate the occurrence and characteristics of azole resistance in A. fumigatus from different parts of China. A total of 317 clinical and 144 environmental A. fumigatus isolates from 12 provinces were collected and subjected to screening for azole resistance. Antifungal susceptibility, cyp51A gene sequencing, and genotyping were carried out for all suspected azole-resistant isolates and a subset of azole-susceptible isolates. As a result, 8 (2.5%) clinical and 2 (1.4%) environmental A. fumigatus isolates were identified as azole resistant. Five azole-resistant strains exhibit the TR34/L98H mutation, whereas four carry the TR34/L98H/S297T/F495I mutation in the cyp51A gene. Genetic typing and phylogenetic analysis showed that there was a worldwide clonal expansion of the TR34/L98H isolates, while the TR34/L98H/S297T/F495I isolates from China harbored a distinct genetic background with resistant isolates from other countries. High polymorphisms existed in the cyp51A gene that produced amino acid changes among azole-susceptible A. fumigatus isolates, with N248K being the most common mutation. These data suggest that the wide distribution of azole-resistant A. fumigatus might be attributed to the environmental resistance mechanisms in China.
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Antifúngicos/farmacología , Aspergilosis/epidemiología , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/genética , Farmacorresistencia Fúngica/efectos de los fármacos , Aspergilosis/tratamiento farmacológico , Aspergilosis/microbiología , Aspergillus fumigatus/aislamiento & purificación , Azoles/farmacología , China/epidemiología , Sistema Enzimático del Citocromo P-450/genética , Farmacorresistencia Fúngica/genética , Proteínas Fúngicas/genética , Humanos , Repeticiones de Microsatélite , FilogeniaRESUMEN
OBJECTIVES: Oral colonization of Candida could lead to later development of oropharyngeal candidiasis or candidemia among the immunocompromised patients. This study aims to describe the occurrence and risk factors of oral Candida colonization in patients with malignancies. MATERIALS AND METHODS: From October 2012 to March 2013, 78 patients with pulmonary cancer (group I), 101 patients with gastrointestinal tract tumor (group II), 79 patients with hematopoietic system malignant tumor (group III), and 101 healthy controls were consecutively recruited in a hospital in Beijing, China. The oral rinse samples were taken and Candida species were identified; the enzymes activities were tested. RESULTS: In total, 110 and 27 Candida strains were isolated from 91 patients and 26 controls, respectively. The oral colonization rate with Candida albicans in group III (12.7 %) was significant lower than that in group I (30.8 %), group II (33.7 %), and control group (25.7 %). The oral colonization rates with non-albicans Candida species in group I, group II, and group III were 15.4, 10.9, and 12.7 %, respectively, while only one non-albicans Candida strain was identified in control group. The non-albicans Candida species exhibited a lower virulence than C. albicans. Age was an independent risk factor for Candida colonization in patients with pulmonary cancer and digestive tract malignant tumor, "Teeth brush <1 time/day" was an independent risk factor for Candida colonization in patients with hematopoietic system tumor. CONCLUSIONS: The differences of risk factors for oral Candida colonization in patients with different cancers require different strategies for the prevention and control of Candida infection. CLINICAL RELEVANCE: Old aged patients with pulmonary cancer and digestive tract malignant tumor are high-risk population for Candida colonization. Increasing frequency of teeth brush might be helpful for preventing Candida colonization.
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Candidiasis Bucal/epidemiología , Candidiasis Bucal/microbiología , Neoplasias Gastrointestinales/complicaciones , Neoplasias Gastrointestinales/inmunología , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/inmunología , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/inmunología , Infecciones Oportunistas/epidemiología , Adulto , Antifúngicos/farmacología , Estudios de Casos y Controles , China/epidemiología , Femenino , Genotipo , Humanos , Huésped Inmunocomprometido , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Cepillado Dental , VirulenciaRESUMEN
Lung epithelial cells constitute the first defense line of host against the inhaled Aspergillus fumigatus; however, the transcriptional response of human alveolar type II epithelial cells was still unclear. Here we used RNA-Seq technology to assess the transcriptome profiles of A549 cells following direct interaction with conidia of A. fumigatus. The total number of identified genes was 19118. Compared with uninfected A549 cells, 459 genes were differentially expressed in cells co-incubated with conidia for 8 h, including 302 up-regulated genes and 157 down-regulated genes. GO and KEGG pathway enrichment analysis showed that most of the up-regulated genes were related to immune response, chemotaxis and inflammatory response and enriched in cytokine-cytokine receptor interaction, JAK-STAT and MAPK signaling pathways. The down-regulated genes were mainly enriched for terms associated with development, hemopoiesis and ion transport. Among them, EGR4 and HIST1H4J gene had the maximum of fold change in up-regulated and down-regulated genes, respectively. Fourteen up-regulated genes and three down-regulated genes were further validated and significant increase on expression of IL-6, IL-8 and TNF-α in A549 cells were confirmed by qRT-PCR during the interaction of A549 cells with A. fumigatus. Besides, western blot showed that expression of two proteins (ARC, EGR1) significantly increased in A549 cells during interaction with A. fumigatus conidia for 8h. Interference of endogenous expression of ARC or EGR1 protein in A549 cells reduced the internalization of A. fumigatus. These results provided important insights into dynamic changes of gene expression in lung epithelial cells, especially its strong immunological response against A. fumigatus infection.
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Células Epiteliales Alveolares/metabolismo , Aspergillus fumigatus/fisiología , Pulmón/metabolismo , Mucosa Respiratoria/metabolismo , Esporas Fúngicas , Transcriptoma , Línea Celular , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Sistema de Señalización de MAP QuinasasRESUMEN
BACKGROUND: The internalization of Aspergillus fumigatus into alveolar epithelial cells (AECs) is tightly controlled by host cellular actin dynamics, which require close modulation of the ADF (actin depolymerizing factor)/cofilin family. However, the role of cofilin in A. fumigatus internalization into AECs remains unclear. RESULTS: Here, we demonstrated that germinated A. fumigatus conidia were able to induce phosphorylation of cofilin in A549 cells during the early stage of internalization. The modulation of cofilin activity by overexpression, knockdown, or mutation of the cofilin gene in A549 cells decreased the efficacy of A. fumigatus internalization. Reducing the phosphorylation status of cofilin with BMS-5 (LIM kinase inhibitor) or overexpression of the slingshot phosphatases also impeded A. fumigatus internalization. Both the C. botulimun C3 transferase (a specific RhoA inhibitor) and Y27632 (a specific ROCK inhibitor) reduced the internalization of A. fumigatus and the level of phosphorylated cofilin. ß-1,3-glucan (the major component of the conidial cell wall) and its host cell receptor dectin-1 did not seem to be associated with cofilin phosphorylation during A. fumigatus infection. CONCLUSION: These results indicated that cofilin might be involved in the modulation of A. fumigatus internalization into type II alveolar epithelial cells through the RhoA-ROCK-LIM kinase pathway.
Asunto(s)
Factores Despolimerizantes de la Actina/metabolismo , Aspergillus fumigatus/fisiología , Endocitosis , Células Epiteliales/microbiología , Interacciones Huésped-Patógeno , Línea Celular , HumanosRESUMEN
Major challenges remain when attempting to quantify and evaluate the impacts of contaminated environments and heterogeneity in the cohorting of health care workers (HCWs) on hospital infections. Data on the detection rate of multidrug-resistant Acinetobacter baumannii (MRAB) in a Chinese intensive care unit (ICU) were obtained to accurately evaluate the level of environmental contamination and also to simplify existing models. Data-driven mathematical models, including mean-field and pair approximation models, were proposed to examine the comprehensive effect of integrated measures including cohorting, increasing nurse-patient ratios and improvement of environmental sanitation on MRAB infection. Our results indicate that for clean environments and with strict cohorting, increasing the nurse-patient ratio results in an initial increase and then a decline in MRAB colonization. In contrast, in contaminated environments, increasing the nurse-patient ratio may lead to either a consistent increase or an initial increase followed by a decline of MRAB colonization, depending on the level of environmental contamination and the cohorting rate. For developing more effective control strategies, the findings suggest that increasing the cohorting rate and nurse-patient ratio are effective interventions for relatively clean environments, while cleaning the environment more frequently and increasing hand washing rate are suitable measures in contaminated environments.
Asunto(s)
Acinetobacter baumannii/patogenicidad , Infección Hospitalaria , Farmacorresistencia Bacteriana Múltiple/genética , Unidades de Cuidados Intensivos , Acinetobacter baumannii/efectos de los fármacos , Brotes de Enfermedades , Humanos , Pruebas de Sensibilidad Microbiana , Modelos TeóricosRESUMEN
In 2008, an intensive care unit (ICU) in a large Chinese hospital was moved from a 6-bed old ward to a 20-bed new ward. After the move, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in patients and environmental sites decreased significantly, but the number of ICU-acquired cases per imported MRSA case increased from 1.4 to 4.1. This study suggests that the nurse cohorting level and hand hygiene compliance are strong predicators of MRSA transmission in ICUs.