The normal microbial flora of the human body includes diverse populations of microorganisms inhabiting different body sites. The composition of the flora varies by body region and is determined by environmental factors like pH, moisture and nutrients. The flora plays important roles in host health, aiding digestion and competing against pathogens. While usually harmless, elements of the flora can cause disease in immunocompromised hosts. The skin flora in particular is dominated by staphylococci and micrococci that vary in concentration between dry and moist skin sites.
2. INTRODUCTION
Skin Flora
• The varied environment of the skin results in locally dense or sparse populations, with
Gram-positive organisms (e.g., staphylococci, micrococci, diphtheroids) usually
predominating.
Oral and Upper Respiratory Tract Flora
• A varied microbial flora is found in the oral cavity, and streptococcal anaerobes inhabit the
gingival crevice. The pharynx can be a point of entry and initial colonization
for Neisseria, Bordetella, Corynebacterium, and Streptococcus spp.
Gastrointestinal Tract Flora
• Organisms in the stomach are usually transient, and their populations are kept low (103 to
106/g of contents) by acidity. Helicobacter pylori is a potential stomach pathogen that
apparently plays a role in the formation of certain ulcer types. In normal hosts the duodenal
flora is sparse (0 to 103/g of contents). The ileum contains a moderately mixed flora (106 to
108/g of contents). The flora of the large bowel is dense (109 to 1011/g of contents) and is
composed predominantly of anaerobes. These organisms participate in bile acid
conversion and in vitamin K and ammonia production in the large bowel. They can also
cause intestinal abscesses and peritonitis.
3. Urogenital Flora
The vaginal flora changes with the age of the individual, the vaginal pH, and hormone
levels. Transient organisms (e.g., Candida spp.) frequently cause vaginitis. The distal
urethra contains a sparse mixed flora; these organisms are present in urine specimens
(104/ml) unless a clean-catch, midstream specimen is obtained.
Conjunctival Flora
The conjunctiva harbors few or no organisms. Haemophilus and Staphylococcus are
among the genera most often detected.
Host Infection
Many elements of the normal flora may act as opportunistic pathogens, especially in
hosts rendered susceptible by rheumatic heart disease, immunosuppression, radiation
therapy, chemotherapy, perforated mucous membranes, etc. The flora of the gingival
crevice causes dental caries in about 80 percent of the population.
4. Introduction
1-A diverse microbial flora is associated with the skin and mucous membranes of every human
being from shortly after birth until death. The human body, which contains about 1013 cells,
routinely harbors about 1014 bacteria. This bacterial population constitutes the normal microbial
flora .
2- The normal microbial flora is relatively stable, with specific genera populating various body
regions during particular periods in an individual's life.
3- Microorganisms of the normal flora may aid the host (by competing for microenvironments
more effectively than such pathogens as Salmonella spp or by producing nutrients the host can
use), may harm the host (by causing dental caries, abscesses, or other infectious diseases), or
may exist as commensals (inhabiting the host for long periods without causing detectable harm
or benefit).
4- Even though most elements of the normal microbial flora inhabiting the human skin, nails,
eyes, oropharynx, genitalia, and gastrointestinal tract are harmless in healthy individuals, these
organisms frequently cause disease in compromised hosts.
5-Viruses and parasites are not considered members of the normal microbial flora by most
investigators because they are not commensals and do not aid the host.Numbers of bacteria
that colonize different parts of the body.
6-Numbers represent the number of organisms per gram of homogenized tissue or fluid or per
square centimeter of skin surface.
5. Significance of the Normal Flora
1-The fact that the normal flora substantially influences the well-being of the host was not well
understood until germ-free animals became available.
2- Germ-free animals were obtained by cesarean section and maintained in special isolators;
this allowed the investigator to raise them in an environment free from detectable viruses,
bacteria, and other organisms.
3-Two interesting observations were made about animals raised under germ-free conditions.
First, the germ-free animals lived almost twice as long as their conventionally maintained
counterparts, and second, the major causes of death were different in the two groups
.
4-Infection often caused death in conventional animals, but intestinal atonia frequently killed
germ-free animals. Other investigations showed that germ-free animals have anatomic,
physiologic, and immunologic features not shared with conventional animals.
5-For example, in germ-free animals, the alimentary lamina propria is underdeveloped, little or
no immunoglobulin is present in sera or secretions, intestinal motility is reduced, and the
intestinal epithelial cell renewal rate is approximately one-half that of normal animals (4 rather
than 2 days).
6-Although the foregoing indicates that bacterial flora may be undesirable, studies with
antibiotic treated animals suggest that the flora protects individuals from pathogens.
6. 7-Investigators have used streptomycin to reduce the normal flora and have then
infected animals with streptomycin-resistant Salmonella. Normally, about
106 organisms are needed to establish a gastrointestinal infection, but in
streptomycin-treated animals whose flora is altered, fewer than 10 organisms
were needed to cause infectious disease.
8-Further studies suggested that fermentation products (acetic and butyric
acids) produced by the normal flora inhibited Salmonella growth in the
gastrointestinal tract.
9-The normal flora in humans usually develops in an orderly sequence, or
succession, after birth, leading to the stable populations of bacteria that make
up the normal adult flora.
10-The main factor determining the composition of the normal flora in a body
region is the nature of the local environment, which is determined by pH,
temperature, redox potential, and oxygen, water, and nutrient levels.
11- Other factors such as peristalsis, saliva, lysozyme secretion, and secretion of
immunoglobulins also play roles in flora control. The local environment is like a
concerto in which one principal instrument usually dominates.
7. 12-For example, an infant begins to contact organisms as it moves through the birth
canal. A Gram-positive population (bifidobacteria arid lactobacilli) predominates in the
gastrointestinal tract early in life if the infant is breast-fed.
13- This bacterial population is reduced and displaced somewhat by a Gram-negative
flora (Enterobacteriaceae) when the baby is bottle-fed. The type of liquid diet provided
to the infant is the principal instrument of this flora control; immunoglobulins and,
perhaps, other elements in breast milk may also be important.
14- Animal and some human studies suggest that the flora influences human anatomy,
physiology, lifespan, and, ultimately, cause of death. Although the causal relationship
of flora to death and disease in humans is accepted, roles of the human microflora
need further study.
8. Normal Flora of Skin
1-Skin provides good examples of various microenvironments. Skin regions have been
compared to geographic regions of Earth: the desert of the forearm, the cool woods of
the scalp, and the tropical forest of the armpit.
2-The composition of the dermal microflora varies from site to site according to the
character of the microenvironment.
3-A different bacterial flora characterizes each of three regions of skin: (1) axilla,
perineum, and toe webs; (2) hand, face and trunk; and (3) upper arms and legs. Skin
sites with partial occlusion (axilla, perineum, and toe webs) harbor more
microorganisms than do less occluded areas (legs, arms, and trunk).
4-These quantitative differences may relate to increased amount of moisture, higher
body temperature, and greater concentrations of skin surface lipids. The axilla,
perineum, and toe webs are more frequently colonized by Gram-negative bacilli than
are drier areas of the skin.
5-The number of bacteria on an individual's skin remains relatively constant; bacterial
survival and the extent of colonization probably depend partly on the exposure of skin
to a particular environment and partly on the innate and species-specific bactericidal
activity in skin.
9. 6-Also, a high degree of specificity is involved in the adherence of bacteria to epithelial
surfaces. Not all bacteria attach to skin; staphylococci, which are the major element of
the nasal flora, possess a distinct advantage over viridans streptococci in colonizing the
nasal mucosa. Conversely, viridans streptococci are not seen in large numbers on the
skin or in the nose but dominate the oral flora.
7-The microbiology literature is inconsistent about the density of bacteria on the skin;
one reason for this is the variety of methods used to collect skin bacteria. The scrub
method yields the highest and most accurate counts for a given skin area.
8-Most microorganisms live in the superficial layers of the stratum corneum and
in the upper parts of the hair follicles. Some bacteria, however, reside in the
deeper areas of the hair follicles and are beyond the reach of ordinary
disinfection procedures. These bacteria are a reservoir for recolonization after
the surface bacteria are removed.
10. Staphylococcus epidermidis
S. epidermidis is a major inhabitant of the skin, and in some areas it makes up more
than 90 percent of the resident aerobic flora.
Staphylococcus aureus
The nose and perineum are the most common sites for S. aureus colonization, which is
present in 10 percent to more than 40 percent of normal adults. S. aureus is prevalent
(67 percent) on vulvar skin. Its occurrence in the nasal passages varies with age, being
greater in the newborn, less in adults. S. aureus is extremely common (80 to 100
percent) on the skin of patients with certain dermatologic diseases such as atopic
dermatitis, but the reason for this finding is unclear.
Micrococci
Micrococci are not as common as staphylococci and diphtheroids; however, they are
frequently present on normal skin. Micrococcus luteus, the predominant species,
usually accounts for 20 to 80 percent of the micrococci isolated from the skin.
11. Diphtheroids (Coryneforms)
1-The term diphtheroid denotes a wide range of bacteria belonging to the genus
Corynebacterium. ‘
2-Classification of diphtheroids remains unsatisfactory; for convenience, cutaneous
diphtheroids have been categorized into the following four groups: lipophilic or
nonlipophilic diphtheroids; anaerobic diphtheroids; diphtheroids producing porphyrins
(coral red fluorescence when viewed under ultraviolet light); and those that possess
some keratinolytic enzymes and are associated with trichomycosis axillaris (infection
of axillary hair).
3- Lipophilic diphtheroids are extremely common in the axilla, whereas nonlipophilic
strains are found more commonly on glabrous skin.
4-Anaerobic diphtheroids are most common in areas rich in sebaceous glands.
Although the name Corynebacterium acnes was originally used to describe skin
anaerobic diphtheroids, these are now classified as Propionibacterium acnes and as P.
granulosum.
12. 5- P. acnes is seen eight times more frequently than P.
granulosum in acne lesions and is probably involved in acne
pathogenesis. Children younger than 10 years are rarely colonized
with P. acnes.
6-The appearance of this organism on the skin is probably related to
the onset of secretion of sebum (a semi-fluid substance composed
of fatty acids and epithelial debris secreted from sebaceous glands)
at puberty. P. avidum, the third species of cutaneous anaerobic
diphtheroids, is rare in acne lesions and is more often isolated from
the axilla.
13. Streptococci
1-Streptococci, especially β-hemolytic streptococci, are rarely seen on normal skin. The
paucity of β-hemolytic streptococci on the skin is attributed at least in part to the
presence of lipids on the skin, as these lipids are lethal to streptococci.
2- Other groups of streptococci, such as α-hemolytic streptococci, exist primarily in the
mouth, from where they may, in rare instances, spread to the skin.
Gram-Negative Bacilli
1-Gram-negative bacteria make up a small proportion of the skin flora. In view of their
extraordinary numbers in the gut and in the natural environment, their scarcity on skin is
striking.
2-They are seen in moist intertriginous areas, such as the toe webs, and not on dry
skin.Desiccation is the major factor preventing the multiplication of Gram-negative
bacteria on intact skin.
3- Enterobacter, Klebsiella, Escherichia coli, and Proteus spp. are the predominant Gram-
negative organisms found on the skin. Acinetobacter spp also occurs on the skin of
normal individuals and, like other Gram-negative bacteria, is more common in the moist
intertriginous areas.
14. Nail Flora
The microbiology of a normal nail is generally similar to
that of the skin. Dust particles and other extraneous
materials may get trapped under the nail, depending on
what the nail contacts. In addition to resident skin flora,
these dust particles may carry fungi and
bacilli. Aspergillus, Penicillium, Cladosporium,
and Mucor are the major types of fungi found under the
nails.
15. Oral and Upper Respiratory Tract Flora
1-The oral flora is involved in dental caries and periodontal disease, which affect about
80 percent. of the population in the Western world.
2- Anaerobes in the oral flora are responsible for many of the brain, face, and lung
infections that are frequently manifested by abscess formation.
3-The pharynx and trachea contain primarily those bacterial genera found in the
normal oral cavity (for example, α-and β-hemolytic streptococci); however, anaerobes,
staphylococci, neisseriae, diphtheroids, and others are also present.
4-Potentially pathogenic organisms such as Haemophilus, mycoplasmas, and
pneumococci may also be found in the pharynx. Anaerobic organisms also are
reported frequently.
16. 5-The upper respiratory tract is so often the site of initial
colonization by pathogens (Neisseria meningitides, C.
diphtheriae, Bordetella pertussis, and many others) and could
be considered the first region of attack for such organisms.
6-In contrast, the lower respiratory tract (small bronchi and
alveoli) is usually sterile, because particles the size of
bacteria do not readily reach it. If bacteria do reach these
regions, they encounter host defense mechanisms, such
as alveolar macrophages, that are not present in the
pharynx.
17. Gastro intestinal microflora:
1-The stomach is a relatively hostile environment for bacteria. It contains bacteria
swallowed with the food and those dislodged from the mouth. Acidity lowers the
bacterial count, which is highest (approximately 103 to 106 organisms/g of contents)
after meals and lowest (frequently undetectable) after digestion.
2-Some Helicobacter species can colonize the stomach and are associated with type B
gastritis and peptic ulcer disease. Aspirates of duodenal or jejunal fluid contain
approximately 103 organisms/ml in most individuals.
3- Most of the bacteria cultured (streptococci, lactobacilli, Bacteroides) are thought to
be transients. Levels of 105 to about 107 bacteria/ml in such aspirates usually indicate
an abnormality in the digestive system (for example, achlorhydria or malabsorption
syndrome).
4-Rapid peristalsis and the presence of bile may explain in part the paucity of
organisms in the upper gastrointestinal tract. Further along the jejunum and into the
ileum, bacterial populations begin to increase, and at the ileocecal junction they reach
levels of 106 to 108 organisms/ml, with streptococci, lactobacilli, Bacteroides, and
bifidobacteria predominating.
18. 5--Concentrations of 109 to 1011 bacteria/g of contents are frequently found in human colon and
feces. This flora includes a bewildering array of bacteria (more than 400 species have been
identified); nonetheless, 95 to 99 percent belong to anaerobic genera such
as Bacteroides, Bifidobacterium, Eubacterium, Peptostreptococcus, and Clostridium.
6-In this highly anaerobic region of the intestine, these genera proliferate, occupy most available
niches, and produce metabolic waste products such as acetic, butyric, and lactic acids. The strict
anaerobic conditions, physical exclusion (as is shown in many animal studies), and bacterial
waste products are factors that inhibit the growth of other bacteria in the large bowel.
7-Anaerobes in the intestinal tract are the primary agents of intra-abdominal abscesses and
peritonitis. Bowel perforations produced by appendicitis, cancer, infarction, surgery, or gunshot
wounds almost always seed the peritoneal cavity and adjacent organs with the normal flora.
8-Anaerobes can also cause problems within the gastrointestinal lumen. Treatment with
antibiotics may allow certain anaerobic species to become predominant and cause disease. For
example, Clostridium difficile, which can remain viable in a patient undergoing antimicrobial
therapy, may produce pseudomembranous colitis.
9- Other intestinal pathologic conditions or surgery can cause bacterial overgrowth in the upper
small intestine. Anaerobic bacteria can then deconjugate bile acids in this region and bind
available vitamin B12 so that the vitamin and fats are malabsorbed.
19. 10-In these situations, the patient usually has been compromised in
some way; therefore, the infection caused by the normal intestinal flora
is secondary to another problem.
11-Research on animals has revealed that unusual filamentous
microorganisms attach to ileal epithelial cells and modify host
membranes with few or no harmful effects. Microorganisms have been
observed in thick layers on gastrointestinal surfaces and in the crypts of
Lieberkuhn.
12- Other studies indicate that the immune response can be modulated
by the intestinal flora. Studies of the role of the intestinal flora in
biosynthesis of vitamin K and other host-utilizable products, conversion
of bile acids (perhaps to cocarcinogens), and ammonia production
(which can play a role in hepatic coma) show the dual role of the
microbial flora in influencing the health of the host. More basic studies
of the human bowel flora are necessary to define their effect on
humans.
20. Urogenital Flora
1-The type of bacterial flora found in the vagina depends on the age, pH, and
hormonal levels of the host. Lactobacillus spp. predominate in female infants (vaginal
pH, approximately 5) during the first month of life.
2-Glycogen secretion seems to cease from about I month of age to puberty. During this
time, diphtheroids, S. epidermidis, streptococci, and E. coli predominate at a higher pH
(approximately pH 7).
3-At puberty, glycogen secretion resumes, the pH drops, and women acquire an adult
flora in which L. acidophilus, corynebacteria, peptostreptococci, staphylococci,
streptococci, and Bacteroides predominate.
4-After menopause, pH again rises, less glycogen is secreted, and the flora returns to
that found in prepubescent females. Yeasts (Torulopsis and Candida) are occasionally
found in the vagina (10 to 30 percent of women); these sometimes increase and cause
vaginitis.
5-In the anterior urethra of humans, S. epidermidis, enterococci, and diphtheroids are
found frequently; E. coli, Proteus, and Neisseria (nonpathogenic species) are reported
occasionally (10 to 30 percent).
6-Because of the normal flora residing in the urethra, care must be taken in clinically
interpreting urine cultures; urine samples may contain these organisms at a level of
104/ml if a midstream (clean-catch) specimen is not obtained.
21. Conjunctival Flora
1-The conjunctival flora is sparse. Approximately 17 to 49 percent of culture samples
are negative. Lysozyme, secreted in tears, may play a role in controlling the bacteria by
interfering with their cell wall formation.
2-When positive samples show bacteria, corynebacteria, Neisseriae, and Moraxellae
are cultured. Staphylococci and streptococci are also present, and recent reports
indicate that Haemophilus parainfluenzae is present in 25 percent of conjunctival
samples.
Host Infection by Elements of the Normal Flora
1-A breach in mucosal surfaces often results in infection of the host by members of the
normal flora. Caries, periodontal disease, abscesses, foul-smelling discharges, and
endocarditis are hallmarks of infections with members of the normal human flora .
2- In addition, impairment of the host (for example, those with heart failure or
leukemia) or host defenses (due to immunosuppression, chemotherapy, or irradiation)
may result in failure of the normal flora to suppress transient pathogens or may cause
members of the normal flora to invade the host themselves.
3- In either situation, the host may die.
22. References
1.Bitton G, Marshall KC: Adsorption of Microorganisms to Surfaces. John Wiley & Sons,
New York, 1980 .
2.Draser BS, Hill MJ: Human Intestinal Flora. Academic Press, London, 1974.
3.Freter R, Brickner J, Botney M. et al. Survival and implantation of Escherichia coli in
the intestinal tract. Infect Immun. 1983;39:686. [PMC free article] [PubMed]
4.Hentges DJ, Stein AJ, Casey SW, Que JU. Protective role of intestinal flora
against Pseudomonas aeruginosa in mice: influence of antibiotics on colonization
resistance. Infect Immun. 1985;47:118. [PMC free article] [PubMed]
5.Herthelius M, Gorbach SL, Mollby R. et al. Elimination of vaginal colonization
with Escherichia coli by administration of indigenous flora. Infect
Immun. 1989;57:2447. [PMC free article] [PubMed]
6.Maibach H, Aly R: Skin Microbiology: Relevance to Clinical Infection. Springer-Verlag,
New York, 1981 .
7.Marples MJ. Life in the skin. Sci Am. 1969;220:108. [PubMed]
8.Savage DC. Microbial ecology of the gastrointestinal tract. Annu Rev
Microbiol. 1977;31:107. [PubMed]
9.Tannock GW: Normal Microflora. Chapman and Hall,London, UK, 1995 .
23. Definitions
1.Infection
An infection is the invasion of an organism's body tissues by disease-causing agents,
their multiplication, and the reaction of host tissues to the infectious agents and
the toxins they produce. An infectious disease, also known as a transmissible
disease or communicable disease, is an illness resulting from an infection.
Infections are caused by infectious agents (pathogens) including:
•Viruses and related agents such as viroids and prions
•Bacteria
•Fungi,
•Parasites
•Arthropods : invasion of a human or animal body by these macroparasites is
usually termed infestation
Hosts can fight infections using their immune system. Mammalian hosts react to
infections with an innate response, often involving inflammation, followed by
an adaptive response. Specific medications used to treat infections
include antibiotics, antivirals, antifungals, antiprotozoals,
and antihelminthics. The branch of medicine that focuses on infections is referred to
as infectious disease.
24. 2-Invasion
The act of invading: as.
a : the penetration of the body of a host by a microorganism.
b : the spread and multiplication of a pathogenic microorganism or of malignant cells
in the body of a host.
3.Pathogen
In biology, a pathogen is anything that can produce disease. A pathogen may
also be referred to as an infectious agent, or simply a germ. Typically, the term
is used to describe an infectious microorganism or agent, such as
a virus, bacterium, protozoan, prion, viroid, or fungus. Small animals, such as
certain kinds of worms and insect larvae, can also produce disease. However,
these animals are usually, in common parlance, referred to as parasites rather
than pathogens. Diseases in humans that are caused by infectious agents are
known as pathogenic diseases, though not all diseases are caused by
pathogens.
4.Pathogenicity
Pathogenicity, or the capacity to cause disease, is a relatively rare quality
among microbes. It requires the attributes of transmissibility or communicability
from one host or reservoir to a fresh host, survival in the new host, infectivity or
the ability to breach the new host's defences, and virulence, a variable that is
multifactorial and denotes the capacity of a pathogen to harm the host.
25. .Virulence
5-Virulence is a pathogen's or microbe's ability to infect or damage a host.
Virulence refers to a pathogen's ability to infect a resistant host. In most other
contexts, especially in animal systems, virulence refers to the degree of
damage caused by a microbe to its host. The pathogenicity of an organism - its
ability to cause disease - is determined by its virulence factors. Virulent can
describe either disease severity or a pathogen's infectivity .
6.Toxigenicity
It is defined as the:
a. Ability of the pathogen to invade and multiply in the host
b. Pathogen's ability to produce disease by the production of a soluble toxin
c.Ability of an agent to produce diseased.
d.Potency of a pathogen measured in terms of the number of microorganisms
required to kill the host
7.Carrier
A person, animal, or plant that harbors and transmits the causative agent of an
infectious disease especially : one who carries the causative agent systemically
but is asymptomatic or immune to it .
26. Disease carrier
Disease carrier could refer to:
•Asymptomatic carrier, a person or organism infected with an infectious disease
agent, but displays no symptoms
•Genetic carrier, a person or organism that has inherited a genetic trait or mutation,
but displays no symptoms
•Transient carriers: The host can be infectious for a short period
•Chronic carrier :The host can be infectious over a prolonged period
•Incubating carriers have been infected and can spread the pathogen, but do not yet
show the symptoms of the illness
•Convalescent carriers continue to spread the pathogen even though they have
recovered from illness.
•Paradoxical carrier: A person is a paradoxical carrier when he acquires the
microorganism from another carrier.
•Biliary Carrier asymptomatic person who sheds typhoid bacteria in stool or
bile
•Urinary Carrier asymptomatic person who sheds typhoid bacteria in urine
27.
28. Disease Transmission
Overview
Infectious diseases are transmitted from person to person by direct or indirect contact.
Certain types of viruses, bacteria, parasites, and fungi can all cause infectious disease.
Malaria, measles, and respiratory illnesses are examples of infectious diseases.
Direct contact
Infectious diseases are often spread through direct contact. Types of direct contact
include:
1. Person-to-person contact
Infectious diseases are commonly transmitted through direct person-to-person contact.
Transmission occurs when an infected person touches or exchanges body fluids with
someone else. This can happen before an infected person is aware of the illness. Sexually
transmitted diseases (STDs) can be transmitted this way.Pregnant women can also
transmit infectious diseases to their unborn children via the placenta. Some STDs,
including gonorrhea, can be passed from mother to baby during childbirth.
29. 2-Direct spread
he spray of droplets during coughing and sneezing can spread an infectious
disease. You can even infect another person through droplets created when you
speak. Since droplets fall to the ground within a few feet, this type of transmission
requires close proximity.
Indirect contact
Infectious diseases can also be spread indirectly through the air and other
mechanisms. For example:
1. Airborne transmission
Some infectious agents can travel long distances and remain suspended in the
air for an extended period of time. You can catch a disease like measles by
entering a room after someone with measles has departed.
2. Contaminated objects
Some organisms can live on objects for a short time. If you touch an object, such
as a doorknob, soon after an infected person, you might be exposed to infection.
Transmission occurs when you touch your mouth, nose, or eyes before
thoroughly washing your hands.Germs can also be spread through contaminated
blood products and medical supplies/instruments.
30. . 3-Food and drinking water
Infectious diseases can be transmitted via contaminated food and water. E. coli is
often transmitted through improperly handled produce or undercooked meat.
Improperly canned foods can create an environment ripe for Clostridium
botulinum, which can lead to botulism.
4. Animal-to-person contact
Some infectious diseases can be transmitted from an animal to a person. This
can happen when an infected animal bites or scratches you or when you handle
animal waste. The Toxoplasma gondii parasite can be found in cat feces.
Pregnant women and people with compromised immune systems should take
extra care (disposable gloves and good hand washing) when changing cat litter,
or avoid it altogether.
5. Animal reservoirs
Animal-to-animal disease transmission can sometimes transfer to humans.
Zoonosis occurs when diseases are transferred from animals to people. Zoonotic
diseases include:
•anthrax (from sheep)
•rabies (from rodents and other mammals)
•West Nile virus (from birds)
•plague (from rodents)
31. .6- Insect bites (vector-borne disease)
Some zoonotic infectious agents are transmitted by insects, especially those that
suck blood. These include mosquitos, fleas, and ticks. The insects become
infected when they feed on infected hosts, such as birds, animals, and humans.
The disease is then transmitted when the insect bites a new host. Malaria, West
Nile virus, and Lyme disease are all spread this way.
7. Environmental reservoirs
Soil, water, and vegetation containing infectious organisms can also be
transferred to people. Hookworm, for example, is transmitted through
contaminated soil. Legionnaires’ disease is an example of a disease that can be
spread by water that supplies cooling towers and evaporative condensers.
32. Lipopolysaccharides(LPS)
(Glycobiology Analysis Manual, 2nd Edition)
1-Lipopolysaccharide (LPS) is the major component of the outer membrane of Gram-
negative bacteria. Lipopolysaccharide is localized in the outer layer of the membrane and
is, in noncapsulated strains, exposed on the cell surface.
Structure
1- Intact bacterial lipopolysaccharides are macromolecules of molecular mass 10-20 kDa
made up of three structural components :
•A hydrophobic lipid section, lipid A, which is responsible for the toxic properties of the molecule,
•A hydrophilic core polysaccharide chain, and
•A repeating hydrophilic O-antigenic oligosaccharide side chain that is specific to the bacterial
serotype.1
2-The lipid A core is made up of a β-glucosamine-(1→6)-glucosamine-1-phosphate base with fatty
acid esters attached to both carbohydrates. The acyl chain length and number of acyl groups may
vary between bacterial species but are relatively conserved within a species.
3- The inner polysaccharide core typically contains between 1 and 4 molecules of the KDO
(3-deoxy-α-D-manno-octulosonic acid) attached to the disaccharide core. KDO is specifically
associated with lipopolysaccharide, and biologically active lipid A was thought to require at least
one KDO residue for bacterial survival.
4-However, an Escherichia coli K-12 suppressor strain that is KDO deficient demonstrates that the
KDO requirement is not absolute for viability.
33. 5-The KDO-containing inner core also is modified with heptulose (ketoheptose) monosaccharides,
the most common of which is L-glycero-α-D-manno-heptopyranose. The inner core glycan residues
are typically phosphorylated or modified with phosphate-containing groups, e.g., pyrophosphate or
2-aminoethylphosphate. The phosphate groups of lipopolysaccharides increase the overall negative
charge of the cell membrane and help to stabilize the structure.
6--The outer core of the lipopolysaccharide contains more common hexoses, including glucose,
galactose, and N-acetylglucosamine and is structurally more diverse than the inner core.
7--The O-antigen is a repeating oligosaccharide unit typically comprised of two to six sugars. The
O-antigen is the primary structural constituent of lipopolysaccharide that differentiates bacteria. The
distinctive O-antigen structures have been used to identify and assign serogroups to Escherichia
coli, Salmonella enterica, and Vibrio cholerae. Lipopolysaccharides from rough mutant strains of E.
coli lack the O-antigen portion of the structure.
8--The core section and the lipid A section of a lipopolysaccharide may have some variability in
structure, while the O-antigen has a high degree of structural variability as well as variability in the
number of repeating units. These differences result in a significant amount of heterogeneity in LPS
preparations.
9-Since LPS is heterogeneous and tends to form aggregates of varying sizes, there is a reported
"molecular mass" range for these aggregates of 1-4 million Dalton or greater. When the LPS is
treated with sodium dodecyl sulfate (SDS) and heat, the molecular mass is ~50-100 kDa.
34. Functions and Applications
1-Within Gram-negative bacteria, the membrane lipopolysaccharides protect the
bacterium against the action of bile salts and lipophilic antibiotics.
2- Lipopolysaccharides are heat stable endotoxins and have long been recognized as a
key factor in septic shock (septicemia) in humans and, more generally, in inducing a
strong immune response in normal mammalian cells. The lipid A moiety has been
identified as critical to the endotoxin activity of lipopolysaccharide.
3- This was demonstrated, Galanos, et al., by finding identical bioactive results, including
endotoxic activity, between synthetic and natural-sourced E. coli lipid A preparations. The
active receptor for lipopolysaccharide has been identified as the CD14/TLR4/MD2
receptor complex, which promotes the secretion of proinflammatory cytokines including
tumor necrosis factor-α and interleukin-1.
4-While the lipid A component is primarily responsible for immune response activation, the
polysaccharide component of Salmonella enterica LPS is also necessary for NF-κB
activation
. 5-Lipopolysaccharide preparations have been used in research for the elucidation of LPS
structure, metabolism, immunology, physiology, toxicity, and biosynthesis.
6-They have also been used to induce synthesis and secretion of growth promoting
factors such as interleukins. Because of its connection to septicemia, lipopolysaccharide
has been studied to identify possible targets for antibodies and inhibitors to LPS
biosynthesis.