Virulence Toxins

VIRULENCE TOXINS
TABLE OF CONTENTS
ABSTRACT Pg: 3
LETHAL TOXIN Pg: 4-5
EDEMA TOXIN Pg: 6
ANTHROLYSIN O Pg: 7
sapM Pg: 8-9
ABSTRACT
The ability of an organism to infect the host and spread disease is
referred to as virulence. The chemicals known as virulence factors help
the bacterium colonise the host at the cellular level. These elements
either have a secretory, membrane-related, or cytosolic character.
Quick adaptive changes in the bacterium's metabolism, physiology, and
morphology are made possible by cytosolic components. The virulence
factors that are connected with the membrane help the bacterium
adhere to and avoid the host cell. In the bacterial arsenal, secretory
factors play a key role in assisting the bacterium in overcoming the
host's innate and adaptive immune response. The secretory virulence
factors of extracellular infections work in concert to harm the host cells.
We revisit the function of a few of the secreted
Bacterial toxins are virulence agents that alter the functioning of the
host cell and seize control of crucial biological functions in order to
promote microbial infection. Some poisons kill innate immune cells
directly, eliminating a significant portion of the host immunological
response.
LETHAL TOXIN
Lethal factor is a Zn2+ metal dependent endoprotease, and to achieve

the active protein conformation, the active site residues (HEXXH)
engage with the divalent metal ion (Zn2+) . Mek 1-4, 6, and 7 are
among the MAP Kinase Kinase (MAPKK) family members that the lethal
factor targets . The intoxicated host cells exhibit a wide range of
phenotypes as a result of the cleavage of the N-terminus of MAPKK
members. The phosphorylation status of host "Heat Shock Protein 27"
(HSP27), which is thought to be crucial for maintaining the permeability
across endothelial cell lining, is reduced as a result of lethal toxin-
mediated cleavage of MAPKK . Since HSP27 activity is controlled by
phosphorylation, anthrax infections are observed to have reduced
membrane permeability.
Polymorphonuclear cells are drawn to the site of the pathogen's
invasion during bacterial infections. The fatal toxin component of the
anthrax toxin system, however, interferes with this vital first response
to the virus. Important chemoattractant cytokine IL-8 is recognised by
neutrophils and is in charge of causing their migration to the site of
damage. According to reports, lethal toxin alters the histone
epigenetics of the IL-8 promoter
EDEMA TOXIN
Another virulence factor of Bacillus anthracis is edoema toxin. Edema
factor functions as an adenylyl cyclase and is activated by calmodulin
and calcium ions. Edema toxin enters the host cell cytoplasm via the PA
translocation channel and converts the cellular pool of adenosine
triphosphate (ATP) to 3′, 5′ cyclic adenosine monophosphate (cAMP), a
secondary messenger important in a variety of cellular processes . A
persistently elevated level of cAMP causes water loss from cells into the
intercellular milieu . The presence of edoema toxin alters the
phosphorylation status of water channels across the cell membrane,
aquaporin-2, activating them for increased water efflux, specifically in
the collecting ducts of the kidney . Excessive water retention is a
problem , which results in fewer NF-B transcription factor binding and
lower IL-8 translation rates . However, the precise chemical
mechanisms by which these alterations happen have not yet been
identified. On the other side, increased IL-8 degradation through deadly
toxin poisoning of the host cells also happens.
ANTHROLYSIN O
Anthrolysin O, which belongs to the Cholesterol Dependent Cytolysins
(CDC) class of cytolysins, is another potent virulence factor secreted by
the virulent strain of Bacillus anthracis. Anthrolysin O causes host cell
death by forming pores in the membrane and disrupting membrane
integrity. The formation of pores results in a diverse set of downstream
signalling, such as increased calcium ion influx in intoxicated cells.
Anthrolysin O disrupts the C2BBE monolayer by changing the
arrangement of Occludin, an integral membrane protein involved in
maintaining the cellular tight junction . Anthrolysin O's cytolytic activity
extends to cell types such as human monocytes, monocyte-derived
macrophages, neutrophils, erythrocytes, and lymphocytes. Anthrolysin
O has haemolytic activity.
SapM
The secreted proteins are the main weapon in Mtb's arsenal against its
host. Raynaud et al. conducted extensive research in 1998, identifying
enzymatic activities in secreted polypeptides from various
mycobacterial species. One of the 24 identified enzymatic activities was
acid phosphatase activity, which was found in culture filtrate protein
fractions from both pathogenic and non-pathogenic strains . Under
acidic conditions, acid phosphatase catalyses the breakdown of
phosphomonoesters (phosphoenolpyruvate, glycerophosphate,
guanosine triphosphate, NADPH, phosphotyrosine, trehalose-6-
phosphate, etc. Two years later, the acid phosphatase responsible for
the observed activity in the culture filtrate protein fraction was
identified as a 28-kDa protein . The presence of a typical prokaryotic
was discovered through N-terminal sequencing.
The ability of acid phosphatases from various other intracellular

pathogens to subdue the respiratory burst of activated human
neutrophils pointed to its role in intracellular survival . Vergne et al.
demonstrated in 2005 that M. tuberculosis var. bovis Bacillus Calmette-
Gue'rin (BCG) SapM could inhibit phagosomal maturation by lowering
membrane-bound lipid phosphatidylinositol 3-phosphate (PI3P)
concentrations [. Rab5, a Rab GTPase, recruits phosphatidylinositol 3-
kinase (PI3K), which in turn phosphorylates Phosphatidylinositol (PI)
converting it into PI3P. PI3P influences the function and cellular
localization of various effector proteins with PI3P binding domains (e.g.,
EEA1). The recruited proteins in turn mediate phagosomal maturation
into phago-lysosome .

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VIRULENCE TOXINS

Lethal factor is a Zn2+ metal dependent endoprotease, and to achieve

The ability of acid phosphatases from various other intracellular

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