FimalEssays ,i, n.) Please discuss the meehanisms that Eordeteiia pertussis, Streptococcus pneumoniaet, Corynebacterium diphtheriae and lufycobacterium tuberculosis utilize to cause disease in the...

1. What Mechanism of action of Bordetella partussis, Streptococcus pneumonia,
Corynebacterium diptheriae, Mycobacterium tuberculosis in respiratory tract disease:
Bordetella partussis causes a respiratory illness commonly known as whooping cough or
pertusis. Bordetella pertussis colonizes the cilia of the mammalian respiratory epithelium and
causes the disease in two stages:
In first stage the bacteria colonizes at the upper respiratory tract and adhere at the wall of the
tract. Adherence is mediated by specific structure on bacterial cell membrane which is called
―filamentous hemagglutinin" (FHA), and cell-bound pertussis toxin (PTx). During this stage it
causes fever, malaise and coughing symptoms.
The second which is known as toxemic stage of pertussis bacteria colonizes within host cell. It
causes paroxysmal and prolonged coughing that often ends in a characteristic inspiratory gasp
(whoop). This stage is mediated by several toxins secreted by bacterial cells. These toxins
include: invasive adenylate cyclase that prevent phagocytic activity of host cell after entering
within it, lethal toxin (also called dermonecrotic toxin) which causes inflammation and local
necrosis adjacent to infection sites, tracheal cytotoxin (a peptidoglycan fragment) which is toxic
for ciliated respiratory epithelium and which will stop the ciliated cells from beating. PTX also
plays a key role in toxemic stage.
Role of transduction in disease causing process:
Bordetella partussis toxin prevents the G protein mediated signal transduction in host cell and
thus kills the cell. Partussis toxin has two subunit: B oligomeric unit and A enzymatic unit. A
subunit of PT has adenosine diphosphate ribosyltransferase activity. This activity causes ADP-
ribosylation of the Cys
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of protein Gi (GTP-binding protein), as well as the corresponding
cysteine of protein Gα and of transducin. These mechanisms prevent the exchange of GDP for
GTP and prevent G protein mediated signal transduction. This mechanism is responsible for
many of the symptoms and signs of pertussis.
Host defense that has to escape by Bordetella pertussis:
Bordetella pertussis secretes several toxins substances that help the bacteria to overcome host
defense. First they have to invade through the cell membrane which is facilitated by filamentous
hemmaglutinin and by pertussis toxin. Then the bacteria have to escape the phagocytic activity
of the macrophages of host cell. This is mediated by the hemmaglutinin that mediate the
phagocytosis of the bacteria by macrophages without oxidative burst that facilitate the bacteria to
survive within host immune cells. B. pertussis possesses all the mechanisms required to attach to
host cells, to evade immune response of host, and to cause damage to the respiratory tract of the
host.
Respiratory disease caused by Streptococcus
pneumonia:
Streptococcus pneumonia, a gram positive
pneumococcal causes pneumococcal pneumonia. This
bacteria adhere the cells of lung and invade the upper
and lower respiratory tract (bronchi, alveoli). These
bacteria adhere and invade the cells with help of
following bacterial molecules:
adherence is mediated by Pneumococcal surface protein C (PspC) ,Pneumococcal surface
antigen A (PsaA), Eno, Phospho-choline, IgA1 protease etc., all of these molecules facilitate the
bacterial cell to adhere and penetrate through the extracellular matrix of the host’s cell.
several transporter system of bacteria such as ABC ransporters, Ami and Plp (Ali) oligopeptide
transporters (involved in competence induction), Piu and Pia iron transporters , Psa manganese
transporter (where PsaA is specifically involved in adherence) , Adc zinc transporter Com
competence system etc facilitate the transport of nutrient to viral cells from host cells.
Internalization and translocation is mediated by PspC (CbpA) bound to the poly-Ig receptor and
Phospho-choline (PC) present in the bacterial cell wall. This is particularly important for the
translocation over the blood-brain barrier during meningitis development. Pneumolysin, a
cholesterol-dependent toxin secreted by bacteria induces apoptosis and kill epithelial cells and
gain access to the subepithelium and cause spread of the organisms.
Role of transduction:
Streptococcus pneumonia spread disease through generalized transduction.
Host defense:
To protect itself from bacterial infection the human host has evolved both innate and adaptive
mechanisms. Epithelial cells can phagocytose and kill bacteria. As Streptococcus
pneumoniae stay in extracellular space, it does not require the intracellular machinery of cells to
replicate and spread. Host’s immune system and epithelial cells produce antibacterial peptides
(cathelicidins and defensins) and proteins (lactoferrin, proteases) that can kill the bacteria.
Infections stimulate and attract several inflammatory substances such as nutrophils,
polymophoneuclear lymphocytes to the site of infection. Accumulation of these substances
causes sequence of chemical and physiological events that prevent the spread of infection. On
infection immune system of host activates complement system and produce antibody which are
crucial for an effective protection against this pathogen.
Escape from host immune system:
Streptococcus pneumonia has evolved several mechanisms to escape host immune response:
 The bacterial cell express cell surface molecule LytA which promotes lyses of the
bacterium which facilitates release of the intracellular toxin, Pneumolysin (Ply). Ply
activates complement and diverts the attack from other bacteria. Ply at higher
concentration promotes lyses of host cell by forming a pore in the cell membrane.
 Surface protein PspA prevents binding C3b and prevent activation of complement
system.
 Surface protein, PspC, prevents factor B binding to C3b to assemble the C3 convertase,
through binds factor H, a negative regulator of the alternative complement system.
 Pneumococcus is able to evade nutrophil net by expressing EndA, a DNA endonuclease
enzyme, that cleaves the DNA and permits escape from the net.
Respiratory disease caused by Corynebacterium diptheriae:
Corynebacterium diptheriae is a causal agent of diphtheria. These bacteria invade the cells of the
respiratory tract and causes pathogenecity in two stages:
First it colonizes at the local tissue of throat and adheres and then invades the cells through
proliferation.
In second stage, toxicogenesis stage bacteria release diphtheria toxin. Diphtheria toxin is a
exotoxin composed of three components: an A (active) domain, a B (binding) domain and a T
(translocation) domain. B domain helps the toxin to bind to the cell membrane and activates the
T domain which helps in insertion of A component into the target cell membrane. A component
has enzymatic action of the toxin which prevents protein synthesis in the host cells and
ultimately kills the cell.
Host’s protective mechanism and escape from it:
The innate immune system provides the first line of defense against infectious diseases;
anatomic barriers such as skin and optimized phagocytic cells (macrophages and neutrophils)
play a main role in innate immunity, antibodies also plays key role in inhibition of infection.
Thus for invasion and spreading in the host cells the bacteria must escape host’s immune
mechanisms. Bacterial exotoxin is very much potent; it helps them to escape from host’s immune
system. Because it immediately causes lysis of cells.
Respiratory disease caused by Mycobacterium tuberculosis:
Mycobacterium tuberculosis causes respiratory disease tuberculosis, TB. These bacteria
aspirated into the lung in aerosol form and invade in the alveolar macrophages. The majority of
these bacilli are destroyed or inhibited. That escape is multiply intracellular and is released after
the death of macrophages. If alive, these bacilli may spread through lymphatic channels or
through the bloodstream to more organs and distant tissues such as kidneys, lymhnodes, brain
etc.
Host immune response and escape from immune system:
Mycobacterium tuberculosis is in a led through air droplet and alveolar macrophages intake
them. Macrophages are designed to kill the bacteria. Thus the first step of escape is avoiding
killing by macrophages. Innate immunity and adaptive immunity play key role in preventing
invasion of Mycobacterium tuberculosis. Immune systems produce several antibodies and other
antimicrobial substances that prevent the spread of disease and ultimately kill the bacteria.
M. tuberculosis is a highly successful intracellular pathogen that has developed strategies to
survive even in the presence of high immune pressure. Mycobacterial lipids are most important
for the bacterium to escape from the host immune response. This lipids include glycolipid,
lipoarabinomannan (LAM), is composed of glycophosphatidyl inositol (GPI) ((Shui, Petzold et
al. 2011). Fast-growing, virulent species carry mannosylated LAM (ManLAM) (Dao, Kremer et
al. 2004) that inhibit phagosomal maturation in macrophages (Fratti, Chua et al. 2003; Hmama,
Sendide et al. 2004; Kang, Azad et al. 2005), thus escape from degradation by macrophages M.
tuberculosis also suppresses T-lymphocyte responses by recruiting mesenchymal stem cells
(MSCs) to the site of infection. Mesenchymal stem cells (MSCs) are attracted by the inflamed
area and recruited at the site of infection and suppress T-cell responses. Mesenchymal stem cells
acts via secretion of NO that inhibit the growth of bacteria and confined the bacteria at a
particular space but it cannot kill the bacteria.
Billions of bacteria are present in our body as mutualistic organism and don’t cause any problem
in the host body. These organisms are called normal flora. Upper respiratory tract and nose are
place of several bacteria such as Staphylococcus aureus, Corynebacterium species, Nisseria
spiece, Neisseria meningitides, C. diphtheriae, Bordetella pertussis etc are normal flora of upper
respiratory tract. These bacteria usually remain as mutualistic or commesial organism. But they
are actually opportunistic pathogen and cause pathogenesis in host cell when they invade in to
the other cells.
Role of personal hygiene, quorum sensing and sequential timing of microbial respiratory
tract disease:
Most of the respiratory tract disease arecontaguous and infectous. Spread of bacteria from an
infected individual occurs through the coughing, exhaled air, sneezing etc. personal hygiene
plays a major role to prevent infections of these bacteria.
Quorum sensing bacteria produce and release chemical signal molecules called autoinducers that
leads to an alteration in gene expression. Through quorum sensing various activity of bacteria
such as competence, symbiosis, sporulation, conjugation, virulence, motility, antibiotic
production, can be determined that is beneficial for controlling the spreading of bacteria.
Sequential timing helps to determine the density of bacteria at a particular time interval.
Receptor mediated process:
Any physiological process that is mediated by receptor on cell membrane is called receptor
mediated process. Receptor mediated endocytosis is a major physiological process, in which a
molecule is internalized within a cell through a cell membrane receptor.
Role of SOD and catalase in Bordetella pertussis infection:
Superoxide dismutase (SOD) and catalase induce synthesis of adenylate cyclase-hemolysin and
pertactin, two factors which are important for B. pertussis pathogenesis.
Obligate aerobes: obligate aerobes are organisms that require oxygen to grow. Without oxygen
they cannot survive.
Example: Mycobacterium tuberculosis (acid-fast). Pseudomonas aeruginosa.
Generalized transduction:
Generalized transduction is a transduction mechanism in which a bacteriophage infect a bacteria
and dusintigrate bacterial DNA. The phage DNA and bacterial DNA are packaged into new viral
particle. When a new viral particle with bacterial DNA is transferred to another bacteria
transduction of bacterial gene occurs.
Specialized transductuction:
In specialized transduction a set of bacterial gene that is adjacent to a phage DNA located in the
chromosome is excised and packaged into a viral particle and the transferred to another
bacterium.
Streptococcus pneumonia spread disease through generalized transduction.
Gene for the diphtheria toxin is carried in genome of a bacteriophage. C. diphtheria strains must
contain a bacteriophage (beta-phage), acquired by specialized transduction from other C.
diphtheria strains, in order to express the toxin.
References:
Shui, W., C. J. Petzold, et al. (2010). "Organelle membrane proteomics reveals differential
influence of mycobacterium lipoglycans on macrophage phagosome maturation and
autophagosome accumulation." J Proteome Res 10(1): 339-48.
Dao, D. N., L. Kremer, et al. (2004). "Mycobacterium tuberculosis lipomannan induces
apoptosis and interleukin-12 production in macrophages." Infect Immune 72(4): 2067-74.
Fratti, R. A., J. Chua, et al. (2003). "Mycobacterium tuberculosis glycosylated
phosphatidylinositol causes phagosome maturation arrest." Proc Natl Acad Sci U S A 100(9):
5437-42.
http://www.ncbi.nlm.nih.gov/books/NBK7813/
http://cid.oxfordjournals.org/content/49/10/1565.full
http://textbookofbacteriology.net/S.pneumoniae.html
http://jmm.sgmjournals.org/content/55/4/355.full
http://www.cdc.gov/tb/education/corecurr/pdf/chapter2.pdf
http://www.ncbi.nlm.nih.gov/books/NBK7617/
http://www.ncbi.nlm.nih.gov/pubmed/11544353
http://www.ncbi.nlm.nih.gov/books/NBK7813/
http://cid.oxfordjournals.org/content/49/10/1565.full
http://textbookofbacteriology.net/S.pneumoniae.html
http://jmm.sgmjournals.org/content/55/4/355.full
http://www.cdc.gov/tb/education/corecurr/pdf/chapter2.pdf
http://www.ncbi.nlm.nih.gov/books/NBK7617/
http://www.ncbi.nlm.nih.gov/pubmed/11544353
2. Clostridium tetani causes nervous disease tetanus which causes muscular spasm, tightening of
muscles and lock jaw. These bacteria are very resistant, their spores can live in the soil, and
animal feces for long time. These bacteria get entry to the human body through punctured
wounds, rusty nails, insects’ bites, splinters, broken skin etc. usually spores of their bacteria enter
to the human body from environment, and it is not transmitted from person to person.
These bacteria produce bacteria toxin (poison) tetanospasmin, which causes tetanus.
Tetanospasmin binds to motor nerves and enters the axons, and through retrogate intraneuronal
transport travels through the axon and reaches the body of the motor nerve in the spinal cord or
brainstem. Then the toxin migrates into the synapse and binds to presynaptic nerve terminals and
inhibits or stops the release of certain inhibitory neurotransmitters (glycine and gamma-
aminobutyric acid). Due to this inhibition the chemical signal to the motor nerve of the muscle
intensifies, resulting in huge continuous contraction or spasm. When tetanospasmin invade in the
bloodstream or lymphatic vessels from the wound site, it can be deposited in many different
presynaptic terminals causing continuous muscle contraction all over the body.
Host immune defense:
On encountering tetanus toxin body’s immune system produce antibodies against this toxin. To
invade and cause disease in the host cells bacteria has to escape from the innate and acquired
immune mechanism of host. If a patient never exposed to this toxin, cannot produce much
antibodies to resist these bacterial growth and invasion. This bacteria can encode several toxins
such as tetanus toxin, tetanolysin, and many proteins and enzymes such as hemolysin, and
fibronectin-binding proteins, surface-layer (S-layer) proteins etc. facilitates the bacteria to
penetrate through the host cell membrane and extracellular matrix and spreading of bacteria.
Methods of preventing Clostridium tetani:
Active immunization ("tetanus shots") plays an essential role in preventing tetanus. Vaccination
is most beneficial. The U.S. Centers for Disease Control and Prevention (CDC) had
recommended two vaccines: for pediatric populations, DTaP (diphtheria, tetanus and acellular
pertussis combination vaccine) and for nonimmunized adults and booster shots, Tdap (tetanus
and reduced amounts of diphtheria and acellular pertussis combination vaccine) is
recommended.
Tetanus-prone people who are not completely immunized should receive a tetanus booster in
addition to tetanus antibodies (human tetanus immune globulin or TIG). The tetanus antibodies
(TIG) will provide short-term protection against the disease.
Prevention of penetration of tetanus bacteria through skin should be prevented.
Clostridium...