Bacterial secretion systems allow bacteria to transport substrates across cell membranes. There are six known classes of secretion systems in Gram-negative bacteria and one additional system in Gram-positive bacteria. These systems transport a variety of substrates that help bacteria acquire nutrients, move, communicate, and cause infection. The systems range from simple transport across the inner membrane alone to complex nanomachines that transport effectors directly into host cells.
bacterial secretion system, tpyes of different secretion system, type 3 secretion system , regulation, effectors role of effectors, host bactrial relation molecular activities of effectors, chaperons, atpase
bacterial secretion system, tpyes of different secretion system, type 3 secretion system , regulation, effectors role of effectors, host bactrial relation molecular activities of effectors, chaperons, atpase
Bacteria- Bacteria, the oldest and most diversified creatures on our planet, have a structure that is both basic and interesting.
Key points-
cell envelope- Investigate the bacterial cell's outermost layers, including the cell wall, cell membrane, and any other components that defend and preserve cell integrity.
cytoplasm and nucleotide- Discover the inner workings of bacterial cells, where genetic material is stored, metabolism occurs, and critical functions are organised.
Appandages and Flagella-Learn about the many appendages that bacteria can have, such as flagella, pili, and fimbriae, and how they help in motility and adherence.
Inclusions and Granules:Learn how bacteria adapt to their surroundings by storing energy and critical chemicals in the form of inclusions and granules.
Structural variation-Explore the variety of bacterial structure across various species and how these changes contribute to their adaptation and success.
Interactions and Ecological Importance: Investigate how bacteria's structure effects their interactions with other species and their significance in ecosystems.
This slide is presented by
Deepti Negi
Assistant professor
Pharmacology
Shri Guru Ram Rai University
Dehradun
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stockrebeccabio
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stock
Telegram: bmksupplier
signal: +85264872720
threema: TUD4A6YC
You can contact me on Telegram or Threema
Communicate promptly and reply
Free of customs clearance, Double Clearance 100% pass delivery to USA, Canada, Spain, Germany, Netherland, Poland, Italy, Sweden, UK, Czech Republic, Australia, Mexico, Russia, Ukraine, Kazakhstan.Door to door service
Hot Selling Organic intermediates
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
2. Introduction
• Bacteria have evolved a remarkable number of pathways for
the transport of substrates across the cell-envelope.
• These systems are multiprotein complexes forming Nano
machines that allow regulated exchanges with the
extracellular milieu.
• The secreted substrates fulfill various functions in processes
such as acquisition of nutrients, motility, and intercellular
communication.
3. • Moreover, bacterial pathogens use these machineries to
secrete harmful toxins, adhesins, degradative enzymes, and
other translocated effectors to help during the colonization of
host organisms.
• The secretion systems used by pathogenic bacteria are
essential for their virulence and are grouped into different
classes according to their mechanism, composition, and
evolutionary relationship.
4. • In Gram-negative bacteria, where secretion involves
translocation across inner and outer membranes, there are
now known six general classes of protein secretion systems,
each of which shows considerable diversity.
• Gram-positive bacteria share some of the same secretion
systems as Gram negative bacteria and also display one
system specific to that group, the type VII system.
5. Secretion across the inner membrane
• The first impediment any protein will encounter when
trying to exit a bacterial cell will be the inner membrane,
regardless of whether the bacterium is Gram-positive or
negative.
• There are three main systems involved in the transport
of proteins through the inner membrane alone:
– The Sec (general secretory, or GSP),
– SRP (signal-recognition particle) and
– Tat (twin-arginine translocation) pathways.
6. • The Sec pathway is produced via the interaction of
several different proteins, which are conserved across
both prokaryotes, and eukaryotes , and is involved in
transport across the membrane of endoplasmic reticulum .
• Several of these proteins are also common to the SRP
system.
7. Secretion across the outer membrane
• Secretion across the outer membrane is by its very
nature a process only undertaken by Gram-negative
bacteria.
• Gram-negative bacteria have evolved a series of
mechanisms which allow them to either export proteins
– as a two-step process, utilising one of the methods
mentioned above to export the protein across the
inner membrane, or
– as a one step process, where the protein is exported
from the cytosol to outside of the cell without any
intermediate steps.
8. Type I Secretion
• Type-I secretions systems (T1SSs) allow for the movement
of proteins from the cytoplasm to outside of the cell in a
one-step manner, utilising a simple system of just three
proteins.
9. • These three proteins are an ATP-
binding cassette (ABC) transporter, a
membrane fusion protein (MFP) and
an outer membrane pore forming
protein (OMP) .
• The ABC protein consists of a
cytoplasmically located nucleotide
binding domain, and a transmembrane
domain produced from six α-helices .
• ABC proteins typically function as
homodimers or trimers in producing a
functional pore through which the
secreted protein can traverse .
10. • It is also the role of the ABC
protein to provide substrate
specificity to the secretion
machinery.
• The MF proteins interact in a
trimeric fashion with the ABC
proteins in order to provide a
periplasmic channel through
which the secreted protein can
travel.
11. • It has been suggested that the
binding of substrates to the ABC
protein leads to a conformational
change in the MFP, such that it
interacts with the OMP to
complete the channel to the
external environment .
• There are a wide variety of
proteins exported by T1S
machinery, from enzymes to
toxins and adhesins .
12. Type II secretion
• Compared to T1SSs, type II secretion systems (T2SSs) are
considerably more complex.
• This is despite the fact that T2SSs only traffic proteins across
the outer membrane.
• In order to traverse the inner membrane a separate secretion
system is required.
• Generally this is done by the Sec pathway , however there is
also evidence of there being type-II secreted proteins exported
through the inner membrane via the Tat system.
13. • The T2SS shows an evolutionary
relationship with the type IV pilus
assembly machinery.
• Indeed, both machineries share a
set of common core components -
the outer membrane secretin
(GspD), the cytoplasmic ATPase
(GspE), an inner transmembrane
protein (GspF), the major (GspG)
and the minor (GspH, I, J, K)
pseudopilins and the pre-
pseudopilin/ pilin peptidase/
methyltransferase (GspA).
14. • T2SSs utilise 12 to 16
proteins in order to effect
secretion through the
outer membrane.
• Perhaps surprisingly
though only a couple of
these are actually located
in the outer membrane .
15. • The remainder of the
proteins are located in
the cytoplasmic membrane
or in the periplasmic
space .
• There is also a
cytoplasmic protein GspE,
which interacts with ATP ,
and presumably acts as
an ATPase, providing
energy to drive the export
of proteins .
16. • The inner membrane located
proteins include several (GspL
and M) which anchor the
ATPase to the apparatus, and
GspF, which may function to
provide a pore for the
translocation of pseudopilins
into the periplasmic space.
• The pseudopilins themselves
are a group of proteins (GspG-
K) which come together to
form a large multimeric
structure called the pseudopilus.
17. • Based on evidence from
several experiments it has
been hypothesised that the
pilus may grow in order to
push secreted molecules
through the outer membrane
complex, or alternatively as a
cork to close off the outer
membrane channel when not
required.
18. • The outer membrane complex of
T2SSs consists of two components,
and pore forming protein GspD,
which exists as a multimer of 12-14
copies and forms the pore in the
outer membrane, and a lipoprotein
GspS.
• GspD and GspS proteins iterate in
a 1:1 stoichiometry , and GspS
serves to aid the localisation of the
GspD multimer into the outer
membrane .
• The pore formed by GspD is
approximately 95Å in diameter, a
size large enough for proteins to
pass through T2SSs in a folded
state
19. Type III secretion
• Type-III secretion systems (T3SSs) are possibly the most
complex of all the secretion systems thus far described.
• They accomplish secretion of proteins from the bacterial
cytoplasm to the cytoplasm of other cells.
• One step process by utilising a needle like appendage
with a tip on the end which allows for a hole to be
made in the cell membrane of the cell into which the
secreted protein will be translocated.
20. • The type III secretion system (T3SS) is found in Gram-negative
bacteria that interact with both plant and animal hosts, either
as pathogens or mutualists .
• The machinery of the T3SS, termed the injectisome, appears
to have a common evolutionary origin with the flagellum.
• The principal known function of the injectisome is to deliver
effector proteins across the bacterial and host membranes
into the cytosol of host cells, where they may modulate a
large variety of host cell functions, including immune and
defense responses and in this supplement .
21. • Some bacteria may harbor more than one T3SS; for example
Salmonella typhimurium contains two pathogenicity islands (SPI-1
and SPI-2), each of which encodes a different T3SS.
• Although up to 25 proteins may be required to assemble an
injectisome, only nine are conserved across all seven families, eight
of which are also conserved in the flagellar apparatus .
• Thus there has been considerable divergence and specialization of
the T3SS.
• In many cases, T3SS genes are encoded in pathogenicity islands
from foreign sources and/or are located on plasmids, and are
commonly subject to horizontal gene transfer .
22. • The structure and function of the injectisome have been well studied in
the animal pathogens Salmonella typhimurium and Yersinia pestis and in
the plant pathogen Pseudomonas syringae.
• The injectisomes are composed of a series of basal rings that span the
bacterial inner and outer membranes, connected to a hollow needle (in
Yersinia), filament (in Salmonella) or pilus in (P. syringae).
• Each structure is tipped with a translocation pore that is inserted into the
plasma membrane of the target cell .
• A conserved ATPase associates with the bacterial cytoplasmic base of the
injectisome and energizes transport.
• Two classes of chaperones aid in assembly of the injectisome, while a third
class assist in translocation of effector proteins .
23. • Type-III secretion systems fulfil
two significantly different roles
with bacteria.
• The first is to act as an assembly
and export system in the
production of the bacterial
flagellum (Flagellar- or F-T3SSs).
• The second is to translocate
effector proteins into the cells of
plants and animals.
• Whilst the majority of these T3SS
secrete pathogenicity factors, this
not always the case and as such
are termed here Non-Flagellar- or
NF-T3SS rather than pathogenic-
T3SS.
24. • As with certain other secretion
systems the apparatus spans both
membranes and the periplasm
creating an apparently continuous
channel through from the cytoplasm
to the external environment.
• This channel is made from a series
of components which form the
channel itself and a series of
accessory components which are
required for the function of the
secretion system.
25. Type IV secretion
• Type IV secretion systems (T4SSs)
are unique amongst the systems
characterised to date in that they
can translocate proteins both in a
one-step and two-step manner.
• Furthermore, T4SSs are not just
limited to the transport of
proteins; they can also function to
transport DNA.
• Once of the best studied T4SSs is
that of Agrobacterium tumefaciens,
which utilises a T4SS to export
transfer-DNA (t-DNA) into
dicotyledonous plants, where the
single stranded DNA which is
transferred contains oncogenes,
resulting in tumour formation in
the plant .
26. • The A. tumefaciens T4SS is
encoded on a plasmid which
contains two operons named virB
and virD , comprising eleven and
five genes respectively.
• The proteins encoded in the virB
operon function as part of the
main secretion apparatus, whilst
the virD operon consists of four
genes which encode proteins
(VirD1,2,3 and 5) involved in the
processing of the t-DNA and one
(VirD4) which couples the t-DNA
to the T4SS.
• As with T2SSs, the VirB proteins
are located in various positions
between the cytoplasm of the
bacteria and the outer membrane.
27. • VirB4 and VirB11 both contain
nucleotide binding domains and
exhibit ATPase activity ,suggesting
that these components provide
energy for the translocation of
proteins through the secretion
system.
• The VirD4 proteins also contains a
Walker A nucleotide-binding motif .
• Of the remaining proteins VirB6,
VirB8 and VirB10 all lie in the inner
membrane.
• Whilst the precise function of these
three proteins is unclear, they all
show a propensity to interact with
several other members of the
secretion system suggesting that
they act as a bridge anchoring the
components of the system together .
28. • VirB8 for example has been
shown to interact with VirB1,
VirB4, VirB8, VirB9, VirB10 and
VirB11 .
• All the remaining six virB operon
proteins have characteristic GSP
type signal sequences, and have
been shown to localise to the
periplasm and outer membrane.
• VirB2 is the pillin subunit, and
assembles together into the T4SS
pilus .
• VirB3 and VirB5 are thought to
interact with the VirB2 pilus, with
there being evidence that VirB5
interacts with VirB2 in a manner
dependant on several other VirB
proteins.
29. • VirB7 and VirB9 interact
together , and help form the
outer membrane pore for
translocation , with VirB9
forming the pore and VirB7
lipoprotein stabilising the
complex , in a situation similar
to GspD and GspS in T2SSs.
• Finally VirB1 has been shown
to localise to the periplasm
where it functions as a
transglycosylase, and is
postulated to aid the biogenesis
of the T4SS by creating a hole
in the periplasm , as well as
interacting with the pilus
proteins VirB2 and VirB5 .
30. Type V secretion
• Type V secretion systems (T5SSs) can be grouped into three main
categories: Type Va – the autotranporters (AT), type Vb – the two
partner system (TPS) and Vc – the oligomeric coiled-coil (Oca) system,
also known as the AT-2 system .
31. • Each of these three sub-systems have several identical characteristics,
which include the presence of a N-terminal GSP signal sequence for
transport through the inner membrane , formation of periplasmic
intermediates and formation of a β-barrel pore in the outer membrane
to permit secretion into the external environment .
32. • However beyond those points there are a number of
differences between the 3 varieties of T5SS.
• For example in the case of the AT and Oca systems the signal
sequence, β-barrel and secreted molecule are all within in a
single protein; TPS systems by contrast encode the β-barrel
and secreted molecule as two separate proteins.
33. • Furthermore, the AT and TPS systems produce a complete
β-barrel through one protein , whilst Oca system must
produce a homotrimer in the periplasm in order to direct
translocation of the secreted molecule through the outer
membrane.
34. • These differences present a series of obstacles for the export of
proteins via these systems. In the case of the TPS systems the
separation of the pore and exported protein means that they are
spatially separated.
• In order to direct the protein to its pore it is necessary to have to
some sort of signal recognition event between the two.
35. • In order for the proteins to associate the secreted protein contains
what is termed a TPS domain in its N-terminal region which interact
specifically with the pore forming protein to initiate translocation
through the outer membrane .
• Oca systems also require regions within the protein to allow for
assembly of the monomers into the trimer necessary for formation of
a complete pore in the outer membrane .
36. Type VI secretion system:
• The type VI secretion machinery (T6SS) is a recently
characterized secretion system that appears to constitute a
phage-tail-spike-like injectisome that has the potential to
introduce effector proteins directly into the cytoplasm of host
cells , analogous to the T3SS and T4SS machineries.
• The T6SS machinery was first noticed as a conserved family of
pathogenicity islands in Gram-negative bacteria, then was
identified as encoding secretory machinery in 2006.
37. • More than a quarter of sequenced bacterial genomes contain
genes for T6SS components, mostly within the proteobacteria,
but also within the planctomycetes and acidobacteria.
• The T6SS is required for virulence in human and animal
pathogens such as Vibrio cholerae, Edwardsiella tarda,
Pseudomonas aeruginosa, Francisella tularensis, and
Burkholderia mallei, and also in plant pathogens such as
Agrobacterium tumefaciens, Pectobacterium atrosepticum
and Xanthomonas oryzae .
38. • Some components of the machinery may also act as effectors,
translocated into host cells.
• For example VgrG-1, which is a component of the Vibrio
cholerae T6SS, contains a C-terminal domain that can enter
macrophages where it cross links actin .
• Overall however, the identities and functions of T6SS effectors
are still poorly understood.
39. Type VII secretion system
• Although Gram-positive bacteria have only a single
membrane, some species, most notably the mycobacteria,
have a cell wall that is heavily modified by lipids, called a
mycomembrane.
• As a result, the genomes of these speciesencode a family of
specialized secretion systems collectively called type VII
section systems (T7SS).
40. • The presence of the T7SS was initially predicted bioinformatically
based on clustering of genes encoding secreted proteins that
lacked signal sequences with those encoding membrane
proteins, ATPases and/or chaperones.
• Sequencing of the Mycobacterium bovis BCG vaccine strain, and
mutational analysis of the ESX-1 cluster in M.tuberculosis
confirmed the hypothesis.
• ESX-1 is also required for virulence and hemolysis in the fish
pathogen Mycobacterium marinum, and for conjugation in the
non-pathogenic species Mycobacterium smegmatis .
41. • Mycobacterial genomes contain up to five T7SS gene clusters
that do not functionally complement one another.
• T7SS gene clusters are also found in the closely related
pathogens Corynebacterium diphtheriae and Nocardia .
• More distantly related gene clusters are also found in the
genomes of pathogenic and non-pathogenic Gram-positive
species that lack mycomembranes such as Streptomyces
species and firmicutes such as Bacillus and Clostridium spp.,
Staphylococcus aureus, Streptococcus agalactiae and Listeria
monocytogenes.
42. • The T7SS is required for virulence in Staphylococcus aureus .
• The structure and operation of the T7SS are still being pieced
together.
• Current models suggest an inner membrane translocation channel
formed by the integral membrane protein Rv3877, and a separate
channel in the mycomembrane composed of as yet unknown
protein(s).
• Chaperone-like ATPases anchored to the inner membrane bind the
C-termini of effectors, which are invariably secreted as
heterodimers.
43. Conclusions
• A vast amount of information has been gathered about protein secretion
in Gram-negative bacteria, spurred on by the realization of the importance
of these pathways in bacterial pathogenesis.
• A wide range of secretion strategies has been uncovered, from simple
one-component systems to complex multicomponent assemblies.
• Relationships with organelle biogenesis mechanisms have informed our
understanding of a number of these pathways.
• However, much is still unknown about the structure of the various
secretion machineries, their molecular mechanisms of action, and
how the machineries themselves are assembled.
• Future work in this direction will answer important cell biological
questions and will also present attractive targets for the development of
antimicrobial therapeutics.