Bordetella pertussis is the causative agent of whooping cough in humans, a disease that has recently experienced a resurgence. In contrast, Bordetella bronchiseptica infects the respiratory tract of various mammalian species, causing a range of symptoms from asymptomatic chronic carriage to acute illness. Both pathogens utilize type III secretion system (T3SS) to deliver the effector protein BteA into host cells. Once injected, BteA triggers a cascade of events leading to caspase 1-independent necrosis through a mechanism that remains incompletely understood. We demonstrate that BteA-induced cell death is characterized by the fragmentation of the cellular endoplasmic reticulum and mitochondria, the formation of necrotic balloon-like protrusions, and plasma membrane permeabilization. Importantly, genome-wide CRISPR-Cas9 screen targeting 19,050 genes failed to identify any host factors required for BteA cytotoxicity, suggesting that BteA does not require a single nonessential host factor for its cytotoxicity. We further reveal that BteA triggers a rapid and sustained influx of calcium ions, which is associated with organelle fragmentation and plasma membrane permeabilization. The sustained elevation of cytosolic Ca2+ levels results in mitochondrial calcium overload, mitochondrial swelling, cristolysis, and loss of mitochondrial membrane potential. Inhibition of calcium channels with 2-APB delays both the Ca2+ influx and BteA-induced cell death. Our findings indicate that BteA exploits essential host processes and/or redundant pathways to disrupt calcium homeostasis and mitochondrial function, ultimately leading to host cell death.IMPORTANCEThe respiratory pathogens Bordetella pertussis and Bordetella bronchiseptica exhibit cytotoxicity toward a variety of mammalian cells, which depends on the type III secretion effector BteA. Moreover, the increased virulence of B. bronchiseptica is associated with enhanced expression of T3SS and BteA. However, the molecular mechanism underlying BteA cytotoxicity is elusive. In this study, we performed a CRISPR-Cas9 screen, revealing that BteA-induced cell death depends on essential or redundant host processes. Additionally, we demonstrate that BteA disrupts calcium homeostasis, which leads to mitochondrial dysfunction and cell death. These findings contribute to closing the gap in our understanding of the signaling cascades targeted by BteA.
- MeSH
- bakteriální proteiny * metabolismus genetika MeSH
- Bordetella bronchiseptica genetika metabolismus účinky léků MeSH
- Bordetella pertussis genetika patogenita metabolismus účinky léků MeSH
- buněčná smrt * účinky léků MeSH
- endoplazmatické retikulum metabolismus účinky léků MeSH
- homeostáza * MeSH
- interakce hostitele a patogenu MeSH
- lidé MeSH
- mitochondrie metabolismus účinky léků MeSH
- sekreční systém typu III metabolismus genetika MeSH
- vápník * metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
More than 783 million people worldwide are currently without access to clean and safe water. Approximately 1 in 5 cases of mortality due to waterborne diseases involve children, and over 1.5 million cases of waterborne disease occur every year. In the developing world, this makes waterborne diseases the second highest cause of mortality. Such cases of waterborne disease are thought to be caused by poor sanitation, water infrastructure, public knowledge, and lack of suitable water monitoring systems. Conventional laboratory-based techniques are inadequate for effective on-site water quality monitoring purposes. This is due to their need for excessive equipment, operational complexity, lack of affordability, and long sample collection to data analysis times. In this review, we discuss the conventional techniques used in modern-day water quality testing. We discuss the future challenges of water quality testing in the developing world and how conventional techniques fall short of these challenges. Finally, we discuss the development of electrochemical biosensors and current research on the integration of these devices with microfluidic components to develop truly integrated, portable, simple to use and cost-effective devices for use by local environmental agencies, NGOs, and local communities in low-resource settings.
- MeSH
- biosenzitivní techniky metody MeSH
- elektrochemické techniky metody MeSH
- lidé MeSH
- mikrobiologie vody * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
In this study we attempted to characterize cellular prion-like protein (PrPC) properties and its possible interactions with metal ions. In the first part of this study we described the structure of prion-like protein, its biochemical properties and its role in human or animal organism. In the next and the most important part we summarized accessible information about the metals and heavy metals which can bind prion-like protein. Especially the heavy metals could have really important role in the process of protein misfolding, but this role is still unknown. In the last section we focused on transmissible spongiform encephalopathies, their incubation period and clinical signs.
- MeSH
- kadmium MeSH
- kovy MeSH
- lidé MeSH
- měď MeSH
- prionové nemoci * MeSH
- priony * MeSH
- PrPC proteiny metabolismus MeSH
- PrPSc proteiny metabolismus patogenita MeSH
- těžké kovy * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
125 stran : tabulky ; 20 cm
Úvod shrnuje výsledky několikaletého výzkumu, který si ověřoval, jak jsou která dělnická povolání postižena chronickými katarálními chorobami a alergickými onemocněními dýchacích cest. Následují stati o přípravě nemocného na lázeňské léčení a předpokladech jeho úspěchu, ústavním a sanatorním režimu, léčbě klimatické, medikamentózní a minerálními vodami, doplňkové léčbě peloidní, fyziatrické, otolaryngologické a bronchoskopické, pohybové léčbě a masáži i o léčebné výživě. Výčet inhalačních léčiv v příloze uzavírá text.
- Konspekt
- Fyzioterapie. Psychoterapie. Alternativní lékařství
- NLK Obory
- rehabilitační a fyzikální medicína
- pneumologie a ftizeologie
- balneologie
- NLK Publikační typ
- kolektivní monografie
