RESUMEN
The Gram-negative human pathogen N. gonorrhoeae (Ngo) quickly attaches to epithelial cells, and large numbers of the bacteria remain on the cell surface for prolonged periods. Ngo invades cells but few viable intracellular bacteria are recovered until later stages of infection, leading to the assumption that Ngo is a weak invader. On the cell surface, Ngo quickly recruits CD46-cyt1 to the epithelial cell cortex directly beneath the bacteria and causes its cleavage by metalloproteinases and Presenilin/γSecretease; how these interactions affect the Ngo lifecycle is unknown. Here, we show Ngo induces an autophagic response in the epithelial cell through CD46-cyt1/GOPC, and this response kills early invaders. Throughout infection, the pathogen slowly downregulates CD46-cyt1 and remodeling of lysosomes, another key autophagy component, and these activities ultimately promote intracellular survival. We present a model on the dynamics of Ngo infection and describe how this dual interference with the autophagic pathway allows late invaders to survive within the cell.
Asunto(s)
Gonorrea/metabolismo , Proteína Cofactora de Membrana/fisiología , Neisseria gonorrhoeae/patogenicidad , Autofagia/fisiología , Adhesión Bacteriana , Línea Celular , Cuello del Útero , Regulación hacia Abajo , Células Epiteliales , Femenino , Fimbrias Bacterianas , Gonorrea/fisiopatología , Humanos , Lisosomas , Proteína Cofactora de Membrana/inmunología , Glicoproteínas de Membrana , Proteínas de la Membrana/metabolismo , Neisseria gonorrhoeae/metabolismo , Cultivo Primario de Células , Isoformas de ProteínasRESUMEN
Members of the genus Neisseria have been isolated from or detected in a wide range of animals, from non-human primates and felids to a rodent, the guinea pig. By means of selective culture, biochemical testing, Gram staining and PCR screening for the Neisseria-specific internal transcribed spacer region of the rRNA operon, we isolated four strains of the genus Neisseria from the oral cavity of the wild house mouse, Mus musculus subsp. domesticus. The isolates are highly related and form a separate clade in the genus, as judged by tree analyses using either multi-locus sequence typing of ribosomal genes or core genes. One isolate, provisionally named Neisseria musculi sp. nov. (type strain AP2031T=DSM 101846T=CCUG 68283T=LMG 29261T), was studied further. Strain AP2031T/N. musculi grew well in vitro. It was naturally competent, taking up DNA in a DNA uptake sequence and pilT-dependent manner, and was amenable to genetic manipulation. These and other genomic attributes of N. musculi sp. nov. make it an ideal candidate for use in developing a mouse model for studying Neisseria-host interactions.
Asunto(s)
Ratones/microbiología , Neisseria/clasificación , Filogenia , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Genes Bacterianos , Boca/microbiología , Tipificación de Secuencias Multilocus , Neisseria/genética , Neisseria/aislamiento & purificación , América del Norte , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
Diarrhea remains a significant cause of morbidity and mortality among children in developing countries. Water, sanitation, and hygiene practices (WASH) have demonstrated improved diarrhea-related outcomes but may have limited implementation in certain communities. This study analyzes the adoption and effect of WASH-based practices on diarrhea in children under age five in the rural Busiya chiefdom in northwestern Tanzania. In a cross-sectional analysis spanning July-September 2019, 779 households representing 1338 under-five children were surveyed. Among households, 250 (32.1%) reported at least one child with diarrhea over a two-week interval. Diarrhea prevalence in under-five children was 25.6%. In per-household and per-child analyses, the strongest protective factors against childhood diarrhea included dedicated drinking water storage (OR 0.25, 95% CI 0.18−0.36; p < 0.001), improved waste management (OR 0.37, 95% CI 0.27−0.51; p < 0.001), and separation of drinking water (OR 0.38, 95% CI 0.24−0.59; p < 0.001). Improved water sources were associated with decreased risk of childhood diarrhea in per-household analysis (OR 0.72, 95% CI 0.52−0.99, p = 0.04), but not per-child analysis (OR 0.83, 95% CI 0.65−1.05, p = 0.13). Diarrhea was widely treated (87.5%), mostly with antibiotics (44.0%) and oral rehydration solution (27.3%). Targeting water transportation, storage, and sanitation is key to reducing diarrhea in rural populations with limited water access.
Asunto(s)
Agua Potable , Administración de Residuos , Estudios Transversales , Diarrea/epidemiología , Diarrea/etiología , Diarrea/prevención & control , Humanos , Lactante , Población Rural , Saneamiento , Tanzanía/epidemiologíaRESUMEN
We have previously shown that treatment with (-)-epigallocatechin-3-gallate (EGCG) inhibited vascularity and tumor growth in human colon cancer xenografts in nude mice (Jung et al: Br J Cancer 84, 2001). In this study, we examined whether endothelial cell death by EGCG is mediated by apoptosis and which molecular mechanisms are involved in this process. EGCG was found to suppress cell growth and induce apoptosis largely through mitochondrial depolarization, activation of caspase-3 and cleavage of DNA fragmentation factor-45 in human endothelial ECV 304 cells. The induction of apoptosis by EGCG was confirmed by cleaved and condensed nuclear chromatin and DNA hypoploidy. These results suggest that EGCG may exert at least part of its anticancer effect by inhibiting angiogenesis through inducing endothelial apoptosis.