Question

 

Decades of extensive research has portrayed Shigella as a master of survival, maintaining the subtle balance between virulence and immune protection. A classic example is the modulation of O-antigen (OAg) chain length in S. flexneri. Chromosomal wzz produces short-chain OAg to maximize the T3SS machinery's exposure to host cells whereas the pHS2 counterpart promotes long-chain OAg to mask S. flexneri from serum complement killing.

 

Answer 1

Yes shingella is the master of survival and can maintain the subtle balance between virulence and immune protection.So,Sshingella is a member of the gram negative enterbacteriaceae family and they can further divided into four species based on serological typing:S.dydenteriae,S.boydii,S.flexneri and S.sonnei.The bacterium crosses the epithelium via M cells, and got induced the phagocytosis by macrophages in the submucosa.shigella quickly activate the macrophage death and interact with the epithalium basolateral surface trigaring the host cell cytoskeleton.Once inside the epithalial cell,they agiain lyse the surrounding phagosome and replicate,before disseminating intracellularly to adjacent cells using actin polymerization.Central to this well-choreographed pathogenesis is the large virulence plasmid (more than 200kbp), which encodes the syringe-like type three secretion system (T3SS) and an arsenal of effector protiens, including several invasion plasmid antigens. Various reviews have been dedicated to Shigella's pathogenesis as well as to eucidate the role of each virulence factors.Survival within host cells poses monumental challenge met by the free living E.coli cousins, namely the detection and eliminated by the host immune system.

Chromosomal wzz produces short-chain OAg to mask S.flexneri from serum complement killing.S.sonnei utilizes a different strategy to attain this same effect.It possesses a unique capsules made of OAg polysaccharides decreasing its invasiveness in return for increased protection addition,Shigella is particularly adept in subversion of the host immune responce, targeting both the innate and adaptive systems.Specially it is known to T lymphocytes via T3SS effector IpaD. These potentially deprive the human host to mount an effective and prolonged adaptive immune responce.The initial process upon Shigella infection is the induction of macrophase pyroptosis, allowing the realese of invading bacteria but compromising its survival by igniting a proinflammatory state.IpaD can meditate a noninflammatory macrophase apoptotic bodies.It is proposed that parallel pathway are complementary to balance the trade off between infectiousness and immune invasion.This same theme also underlies the function of the IpaH family, a bacteria E3 ubiquitin ligase of research interest in recent years.This enzyme catalyses the liganation of ubiquintin to target eukaryotic host protiens, usually designating them for degradation via proteasomes.Shigella carries numerous IpaH genes (situated both on chromosomes and the virulence plasmid), which potencially affect ubiquitination in differing protien substrates.Indeed, IpaH7.8 targets glomolin for proteolysis, thus indirectly activating inflammasomes and leading to macrophase pyroptosis.In contrast, IpaH1.4 and 2.5 were shown to suppress the NF-kB immune signalling by interfaring with the linear ubiquitin chain assembly comlex(LUBAC)machinery. Immune suppresion is also achieved thorugh the IpaH9.8-mediated destruction of the interfeon -induced guanylate-binding protiens(GBPs), and this circumvents and the host's cell-autonomus defence against intercellular microbes.In this degradation the promoting cell to cell dissemination in Shigella infection.The maintainance of the large virulence plasmid comes with a significant matabolic cost, which could be detrimental to shigella's survival in resource limited enviroments outside the host.It may contaract with expenditure by integrating pINV into the chromosome, thus down regulating the expression of virulence genes.This phenomenon has been observed in vitro duringS. flexneri's growth at envairomental temperatures and reversible pINV excision restores at some higer room temerature.