RESUMEN
The Gram-negative bacterium Haemophilus influenzae (H. influenzae) can commensally colonize the upper respiratory tract, but also cause life threatening disease including epiglottitis, sepsis and meningitis. The H. influenzae capsule protects the bacteria against both phagocytosis and opsonization. Encapsulated H. influenzae strains are classified into serotypes ranging from a to f dependent on their distinct polysaccharide capsule. Due to the implementation of vaccination the incidence of invasive H. influenzae type b (Hib) infections has strongly decreased and infections with other capsulated types, including H. influenzae type f (Hif), are emerging. The pathogenesis of H. influenzae meningitis is not clarified. To enter the central nervous system (CNS) the bacteria generally have to cross either the blood-brain barrier (BBB) or the blood-cerebrospinal fluid barrier (BSCFB). Using a cell culture model of the BCSFB based on human choroid plexus papilloma (HIBCPP) cells and different H. influenzae strains we investigated whether Hib and Hif invade the cells, and if invasion differs between encapsulated vs. capsular-deficient and fimbriated vs. non-fimbriated variants. We find that Hib can adhere to and invade into HIBCPP cells. Invasion occurs in a strongly polar fashion, since the bacteria enter the cells preferentially from the basolateral "blood "side. Fimbriae and capsule attenuate invasion into choroid plexus (CP) epithelial cells, and capsulation can influence the bacterial distribution pattern. Finally, analysis of clinical Hib and Hif isolates confirms the detected invasive properties of H. influenzae. Our data point to roles of capsule and fimbriae during invasion of CP epithelial cells.
Asunto(s)
Adhesión Bacteriana/fisiología , Cápsulas Bacterianas/patología , Barrera Hematoencefálica/microbiología , Fimbrias Bacterianas/patología , Infecciones por Haemophilus/patología , Haemophilus influenzae/patogenicidad , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Haemophilus influenzae/clasificación , Haemophilus influenzae/aislamiento & purificación , Interacciones Huésped-Patógeno/fisiología , HumanosRESUMEN
Vibrio vulnificus, carrying a 50% fatality rate, is the most deadly of the foodborne pathogens. It occurs in estuarine and coastal waters and it is found in especially high numbers in oysters and other molluscan shellfish. The biology of V. vulnificus, including its ecology, pathogenesis, and molecular genetics, has been described in numerous reviews. This article provides a brief summary of some of the key aspects of this important human pathogen, including information on biotypes and genotypes, virulence factors, risk factor requirements and the role of iron in disease, association with oysters, geographic distribution, importance of salinity and water temperature, increasing incidence associated with global warming. This article includes some of our findings as presented at the "Vibrios in the Environment 2010" conference held in Biloxi, MS.
Asunto(s)
Enfermedades Transmitidas por los Alimentos/microbiología , Ostreidae/microbiología , Mariscos/microbiología , Vibriosis/microbiología , Vibrio vulnificus/patogenicidad , Animales , Cápsulas Bacterianas/inmunología , Cápsulas Bacterianas/patología , Calentamiento Global , Humanos , Hierro/metabolismo , Factores de Riesgo , Salinidad , Agua de Mar/microbiología , Sepsis/microbiología , Sepsis/patología , Temperatura , Vibriosis/patología , Vibrio vulnificus/clasificación , Factores de Virulencia/metabolismo , Microbiología del AguaRESUMEN
Polysaccharide (PS) capsules are important virulence determinants for many bacterial pathogens. Bordetella pertussis, the agent of whooping cough, produces a surface associated microcapsule but its role in pertussis pathogenesis remained unknown. Here we showed that the B. pertussis capsule locus is expressed in vivo in murine lungs and that absence of the membrane-associated protein KpsT, involved in the transport of the PS polymers across the envelope, but not the surface-exposed PS capsule itself, affects drastically B. pertussis colonization efficacy in mice. Microarray analysis revealed that absence of KpsT in B. pertussis resulted in global down-regulation of gene expression including key virulence genes regulated by BvgA/S, the master two-component system. Using a BvgS phase-locked mutant, we demonstrated a functional link between KpsT and BvgA/S-mediated signal transduction. Whereas pull-down assays do not support physical interaction between BvgS sensor and any of the capsule locus encoded proteins, absence of KpsT impaired BvgS oligomerization, necessary for BvgS function. Furthermore, complementation studies indicated that instead of KpsT alone, the entire PS capsule transport machinery spanning the cell envelope likely plays a role in BvgS-mediated signal transduction. Our work thus provides the first experimental evidence of a role for a virulence-repressed gene in pertussis pathogenesis.