Castellani & Chalmers 1919
Shigella flexneri is a species of Gram-negative bacteria in the genus Shigella that can cause diarrhea in humans. Several different serogroups of Shigella are described; S. flexneri belongs to group B. S. flexneri infections can usually be treated with antibiotics, although some strains have become resistant. Less severe cases are not usually treated because they become more resistant in the future.
Bacteria are a type of biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a number of shapes, ranging from spheres to rods and spirals. Bacteria were among the first life forms to appear on Earth, and are present in most of its habitats. Bacteria inhabit soil, water, acidic hot springs, radioactive waste, and the deep portions of Earth's crust. Bacteria also live in symbiotic and parasitic relationships with plants and animals. Most bacteria have not been characterised, and only about half of the bacterial phyla have species that can be grown in the laboratory. The study of bacteria is known as bacteriology, a branch of microbiology.
Shigella is a genus of Gram-negative, facultative aerobic, nonspore-forming, nonmotile, rod-shaped bacteria genetically closely related to E. coli. The genus is named after Kiyoshi Shiga, who first discovered it in 1897.
A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their cell surface antigens, allowing the epidemiologic classification of organisms to the sub-species level. A group of serovars with common antigens is called a serogroup or sometimes serocomplex.
The species was named after the American physician Simon Flexner; the genus is named for Japanese physician Kiyoshi Shiga, who researched the cause of dysentery.
Simon Flexner, M.D. was a physician, scientist, administrator, and professor of experimental pathology at the University of Pennsylvania (1899–1903). He served as the first director of the Rockefeller Institute for Medical Research (1901–1935) and a trustee of the Rockefeller Foundation. He was also a friend and adviser to John D. Rockefeller Jr..
Kiyoshi Shiga was a Japanese physician and bacteriologist.
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S. flexneri contains a virulence plasmid that codes for three virulence factors: a type-3 secretion system (T3SS), invasion plasmid antigen proteins (ipa proteins), and IcsA (used for cell-to-cell spread).
Upon infection, S. flexneri injects the host cell cytoplasm with ipa proteins using the T3SS—a needle-and-syringe-like apparatus common to many Gram-negative pathogens. These ipa proteins induce "membrane ruffling" by the host cell. Membrane ruffling creates membrane pockets which capture and engulf the bacteria. Once inside, S. flexneri uses host cell actin for propulsion to move directly from cell to cell using a cellular mechanism known as paracytophagy,similarly to the bacterial pathogen Listeria monocytogenes .
Paracytophagy is the cellular process whereby a cell engulfs a protrusion which extends from a neighboring cell. This protrusion may contain material which is actively transferred between the cells. The process of paracytophagy was first described as a crucial step during cell-to-cell spread of the intracellular bacterial pathogen Listeria monocytogenes, and is also commonly observed in Shigella flexneri. Paracytophagy allows these intracellular pathogens to spread directly from cell to cell, thus escaping immune detection and destruction. Studies of this process have contributed significantly to our understanding of the role of the actin cytoskeleton in eukaryotic cells.
Listeria monocytogenes is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the host's cells and is one of the most virulent foodborne pathogens, with 20 to 30% of foodborne listeriosis infections in high-risk individuals may be fatal. Responsible for an estimated 1,600 illnesses and 260 deaths in the United States annually, listeriosis ranks third in total number of deaths among foodborne bacterial pathogens, with fatality rates exceeding even Salmonella spp. and Clostridium botulinum. In the European Union, listeriosis follows an upward trend that began in 2008, causing 2,161 confirmed cases and 210 reported deaths in 2014, 16% more than in 2013. Listeriosis mortality rates in the US are also higher in the EU than for other foodborne pathogens.
S. flexneri is able to inhibit the acute inflammatory response in the initial stage of infectionby using an effector protein, OspI, which is encoded by ORF169b on the Shigella large plasmid and secreted by the type III secretion system. It dampens the inflammatory response during bacterial invasion by suppressing the TNF-α-receptor-associated factor 6 (TRAF6)-mediated signalling pathway. OspI has glutamine deamidase activity, and is able to selectively deaminate glutamine at position 100 in UBC13 to glutamate, and this results in a failure of the E2 ubiquitin-conjugating activity which is required for TRAF6 activation.
TRAF6 is a TRAF human protein.
Glutamine is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, polar amino acid. It is non-essential and conditionally essential in humans, meaning the body can usually synthesize sufficient amounts of it, but in some instances of stress, the body's demand for glutamine increases, and glutamine must be obtained from the diet. It is encoded by the codons CAA and CAG.
Ubiquitin-conjugating enzyme E2 N is a protein that in humans is encoded by the UBE2N gene.
Bacterial small RNAs play important roles in many cellular processes. RnaG and RyhB sRNAs have been well studied in S. flexneri.Ssr1 sRNA, which could play role in resistance to acidic stress and regulation of virulence was shown to exist only in Shigella.
Bacterial small RNAs (sRNA) are small RNAs produced by bacteria; they are 50- to 500-nucleotide non-coding RNA molecules, highly structured and containing several stem-loops. Numerous sRNAs have been identified using both computational analysis and laboratory-based techniques such as Northern blotting, microarrays and RNA-Seq in a number of bacterial species including Escherichia coli, the model pathogen Salmonella, the nitrogen-fixing alphaproteobacterium Sinorhizobium meliloti, marine cyanobacteria, Francisella tularensis, Streptococcus pyogenes, the pathogen Staphylococcus aureus, and the plant pathogen Xanthomonas oryzae pathovar oryzae. Bacterial sRNAs affect how genes are expressed within bacterial cells via interaction with mRNA or protein, and thus can affect a variety of bacterial functions like metabolism, virulence, environmental stress response, and structure.
RnaG is a small regulatory non-coding RNA encoded by the virulence plasmid of Shigella flexneri, a Gram-negative pathogenic bacterium that causes human bacillary dysentery. It is a first regulatory RNA characterised in S. flexneri. The RNA is 450 nucleotides long and it contains a region with specific secondary structure that interacts with icsA mRNA and forms a transcription terminator. Acting as antisense, RnaG is transcribed from the complementary strand of its target, icsA mRNA. The activity of the incA protein is crucial for spreading of the bacterial pathogen in the host cells.
RyhB RNA is a 90 nucleotide RNA that down-regulates a set of iron-storage and iron-using proteins when iron is limiting; it is itself negatively regulated by the ferric uptake repressor protein, Fur.
Secretion is the movement of material from one point to another, e.g. secreted chemical substance from a cell or gland. In contrast, excretion, is the removal of certain substances or waste products from a cell or organism. The classical mechanism of cell secretion is via secretory portals at the cell plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structure at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.
In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs). A phagosome is formed by the fusion of the cell membrane around a microorganism, a senescent cell or an apoptotic cell. Phagosomes have membrane-bound proteins to recruit and fuse with lysosomes to form mature phagolysosomes. The lysosomes contain hydrolytic enzymes and reactive oxygen species (ROS) which kill and digest the pathogens. Phagosomes can also form in non-professional phagocytes, but they can only engulf a smaller range of particles, and do not contain ROS. The useful materials from the digested particles are moved into the cytosol, and waste is removed by exocytosis. Phagosome formation is crucial for tissue homeostasis and both innate and adaptive host defense against pathogens.
Borrelia burgdorferi is a bacterial species of the spirochete class of the genus Borrelia. B. burgdorferi exists in North America and Europe and until 2016 was the only known cause of Lyme disease in North America. Borrelia species are considered diderm (double-membrane) bacteria rather than Gram-positive or negative.
Virulence factors are molecules produced by bacteria, viruses, fungi, and protozoa that add to their effectiveness and enable them to achieve the following:
Pascale Cossart is a bacteriologist at the Pasteur Institute of Paris, and the foremost authority on Listeria monocytogenes, a deadly and common food-borne pathogen responsible for encephalitis, meningitis, bacteremia, gastroenteritis, and other diseases.
Type three secretion system is a protein appendage found in several Gram-negative bacteria.
The PrfA thermoregulator UTR is an RNA thermometer found in the 5' UTR of the prfA gene. In Listeria monocytogenes, virulence genes are maximally expressed at 37 °C but are almost silent at 30 °C. The genes are controlled by PrfA, a transcriptional activator whose expression is thermoregulated. It has been shown that the untranslated mRNA (UTR) preceding prfA, forms a secondary structure, which masks the ribosome binding region. It is thought that at 37 °C, the hairpin structure 'melts' and the SD sequence is unmasked.
Listeriolysin O (LLO) is a hemolysin produced by the bacterium Listeria monocytogenes, the pathogen responsible for causing listeriosis. The toxin may be considered a virulence factor, since it is crucial for the virulence of L. monocytogenes.
Virulence-related outer membrane proteins are expressed in Gram-negative bacteria and are essential to bacterial survival within macrophages and for eukaryotic cell invasion.
Listeria monocytogenes is a gram positive bacterium and causes many food-borne infections such as Listeriosis. This bacteria is ubiquitous in the environment where it can act as either a saprophyte when free living within the environment or as a pathogen when entering a host organism. Many non-coding RNAs have been identified within the bacteria genome where several of these have been classified as novel non-coding RNAs and may contribute to pathogenesis.
The Actin assembly-inducing protein (ActA) is a protein encoded and used by Listeria monocytogenes to propel itself through a mammalian host cell. ActA is a bacterial surface protein comprising a membrane-spanning region. In a mammalian cell the bacterial ActA interacts with the Arp2/3 complex and actin monomers to induce actin polymerization on the bacterial surface generating an actin comet tail. The gene encoding ActA is named actA or prtB.
Listeria phage P100 is a virus of the family Myoviridae, genus Twortlikevirus.
Bacterial effectors are proteins secreted by pathogenic bacteria into the cells of their host, usually using a type 3 secretion system (TTSS/T3SS), a type 4 secretion system (TFSS/T4SS) or a Type VI secretion system (T6SS). Some bacteria inject only a few effectors into their host’s cells while others may inject dozens or even hundreds. Effector proteins may have many different activities, but usually help the pathogen to invade host tissue, suppress its immune system, or otherwise help the pathogen to survive. Effector proteins are usually critical for virulence. For instance, in the causative agent of plague, the loss of the T3SS is sufficient to render the bacteria completely avirulent, even when they are directly introduced into the bloodstream. Gram negative microbes are also suspected to deploy bacterial outer membrane vesicles to translocate effector proteins and virulence factors via a novel membrane vesicle trafficking secretory pathway, in order to modify their environment or attack/invade target cells, for example, at the host-pathogen interface.
Daniel A. Portnoy is a microbiologist, the Edward E. Penhoet Distinguished Chair in Global Public Health and Infectious Diseases, and a Professor of Biochemistry, Biophysics and Structural Biology in the Department of Molecular and Cell Biology and in the Division of Microbiology in the Department of Plant and Microbial Biology at the University of California, Berkeley. He is one of the world's foremost experts on Listeria monocytogenes, the bacterium that causes the severe foodborne illness Listeriosis. He has made seminal contributions to multiple aspects of bacterial pathogenesis, cell biology, innate immunity, and cell mediated immunity using L. monocytogenes as a model system and has helped to push forward the use of attenuated L. monocytogenes as an immunotherapeutic tool in the treatment of cancer.
Bacterial secretion systems are protein complexes present on the cell membranes of bacteria for secretion of substances. Specifically, they are the cellular devices used by pathogenic bacteria to secrete their virulence factors to invade the host cells. They can be classified into different types based on their specific structure, composition and activity. These major differences can be distinguished between Gram-negative and Gram-positive bacteria. But the classification is by no means clear and complete. There are at least eight types specific to Gram-negative bacteria, four to Gram-positive bacteria, while two are common to both. Generally, proteins can be secreted through two different processes. One process is a one-step mechanism in which proteins from the cytoplasm of bacteria are transported and delivered directly through the cell membrane into the host cell. Another involves a two-step activity in which the proteins are first transported out of the inner cell membrane, then deposited in the periplasm, and finally through the outer cell membrane into the host cell.
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