Understand the concept of microbiota

Appreciate the range of normal microbiota

Understand the importance of surface infections

Describe the range and origins of surface infections on both natural and prosthetic surfaces

Describe the pathogenesis of infections at a surface

Describe the management of infected surfaces

Describe the different types of hypersensitivity reaction

Understand the pathophysiology behind the types of hypersensitivity reaction

Appreciate the clinical significance of hypersensitivity reactions

is the term used to describe the various bacteria and fungi that are

permanent residents of certain body sites

The viruses and parasites, which are the two other major groups of microorganisms, are

usually not considered members of the normal flora, although they can be present in

asymptomatic individuals.

The members of the normal flora vary in both number and kind from one site to another.

Normal flora organisms inhabit the body surfaces exposed to the environment, such as

the skin, oropharynx, intestinal tract, and vagina. Members of the normal flora differ

in number and kind at various anatomic sites

the internal organs usually are sterile areas such as the central nervous system, blood, lower bronchi and alveoli, liver, spleen, kidneys, and bladder are free of all but the occasional transient organism.

• Members of the normal flora are low-virulence organisms. In their usual anatomic site, they are nonpathogenic. However, if they leave their usual anatomic site, especially in an immunocompromised individual, they can cause disease.

• Colonization resistance occurs when members of the normal flora occupy receptor sites on the skin and mucosal surfaces, thereby preventing pathogens from binding to those receptors.

Sterile (Microbe-Free) Anatomical Sites

and Fluids

Sites That Harbor Normal Resident

Microbes

All Internal Tissues and Organs

Heart and circulatory system Bones

Liver Ovaries/testes

Kidneys and bladder Glands (pancreas, salivary)

Lungs Sinuses

Brain and spinal cord Middle and inner ear

Muscles Internal eye

Fluids Within an Organ or Tissue

Blood

Urine in kidneys, ureters, bladder

Cerebrospinal fluid

Saliva prior to entering the oral cavity

Semen prior to entering the urethra

Amniotic fluid surrounding the embryo and fetus

• Skin and its contiguous mucous

membranes

• Upper respiratory tract (oral cavity,

pharynx, nasal mucosa)

• Gastrointestinal tract (mouth, colon,

rectum, anus)

• Outer opening of urethra

• External genitalia

• Vagina

• External ear and canal

• External eye (lids, lash follicles)

▪ Resident NF – consists of relatively fixed types of microorganisms

regularly found in a given area at a given age; if disturbed, it promptly

reestablishes itself.

▪ Transient NF –consists of nonpathogenic or potentially pathogenic

microorganisms that inhabit the skin or mucous membranes for hours,

days, or weeks; it is derived from the environment, does not produce

disease, and does not establish itself permanently on the surface.

1.Local Environment (pH, temperature,

O2, H2O, and nutrient levels…).

2. Diet

3. Age

4. Health condition (immune activity)

5. Antibiotics

▪ Healthy fetus, in utero, is essentially free of MOs

▪ Infant exposed immediately to MOs when passing

through mothers vaginal tract and then to MOs in

environment

▪ Within few hours, oral and nasopharyngeal flora of

neonate established

▪ Within one day, resident flora of lower intestinal tract

established

Protection from External Invaders

a) Because of the normal flora occupy body's epithelial surfaces, they are able to prevent other bacteria by blocking receptors that

can interfere with colonization by pathogenic bacteria . The ability of members of the normal flora to limit the growth of

pathogens is called colonization resistance .

b) competing for essential nutrients

c) producing anti-bacteria substances e.g : Fatty acids, peroxides , Bacteriocins

May be source of opportunistic infections

e.g : In Patients with impaired defense Mechanisms . For example , antibiotics can reduce the normal colonic flora that

predisposes to pseudomembranos colitis caused by Clostridium difficile .

Nutrition Some of the normal intestinal flora e.g. E. coli & Bacteroids produce Vitamin K in the gut and aid in digestion and

absorption of nutrients.

Important Members of the Normal Flora

Objective 3

Skin. The predominant member of the normal flora of

the skin is Staphylococcus epidermidis. It is an

important cause of infections of prosthetic heart valves

and prosthetic joints.

Candidia albicans, a yeast also found on the skin, can

enter the bloodstream and cause disseminated infections,

such as endocarditis in intravenous drug users. S. aureus

is also present on the skin, but its main site is in the

nose. It causes abscesses in the skin and in many other

organs.

Oropharynx. The main members of the

normal flora of the mouth and throat

are the viridans streptococci, such as

S. sanguis and S. mutans . Viridans

streptococci are the most common cause

of subacute endocarditis.

Examples of bacteria that

inhabit the gastrointestinal

tract.

Gastrointestinal tract. The stomach contains very few organisms

because of the low pH. The colon containsthe largest number of

normal flora and the most diverse species, including both anaerobic and

facultative bacteria. There are both gram-positive and gram-negative rods

and cocci.

The members of the colonic normal flora are an important cause of disease

outside of the colon. The two most important members of the colonic flora

that cause disease are the anaerobe Bacteroides fragilis and the

facultative Escherichia coli. Enterococcus faecalis, a facultative, is

also a very important pathogen.

Vagina. Lactobacilli are the predominant normal flora organisms in the vagina.They keep the pH of the vagina low, which inhibits the growth of organisms such as C. albicans, an important cause of vaginitis.

Urethra. The outer third of the urethra contains a mixture of bacteria, primarily S. epidermidis . The female urethra can become colonized with fecal flora such as E. coli , which predisposes to urinary tract infections.

Associations between microbes and

humans. Effects of contact with

microbes can progress in a variety of

directions, ranging from no effect to

colonization, and from infection to

disease and immunity. The example

shown here follows the possible events in

the case of contact with a pathogen such

as Streptococcus pneumoniae (the

pneumococcus). This bacterium can be

harbored harmlessly in the upper

respiratory tract, but it may also invade

and infect the ear, cranium, and

respiratory tract.

•The two main ways in which an individual will encounter a pathogen are:

where the normal microbiota can multiply and develop due to a disruption of normal defences

result when infecting bacteria have been acquired from an external source and is not part of the natural microbiota

Pili (fimbriae): Are hairlike filaments that extend from the cell surface , they are shorter and straighter than flagella and composed of subunits of aprotein , pilin. They mediate attachment of bacteria to specific receptors witch is necessary step in initiation of infection . For example, Escherichia coli

Glycocalyx (Slime layer): Is a polysaccharide coating that is secreted by many bacteria . It cover surface like afilm and allows the bacteria to adhere firmly to various surface such as skin, heart, valves, and catheters .Streptococcus mutans adhere to the surface of teeth lead to formation of plaque the precursor of dental caries .

Capsule : Is a gelatinous layer covering the entire bacterium . It is composed of polysaccharide except inthe anthrax bacillus which have capsule of polymerized D-glutamic acid . Poly- saccharide capsuleprevent phagocyte from adhering to bacteria.

M protein: Extend from an anchor in the cell membrane , through the cell wall and then thecapsule and exposed on the surface of the bacterium. M protein are antiphagocytic and theyform a coat that interferes with complement binding. Streptococcus pyogenes attach to thepharyngeal mucosa via action M protein and cause pharyngitis.

Protein A : Is the major protein in cell wall of Staphylococcus aureus, it is an importantvirulence factor because it bind to the Fc portion of IgG at the complement binding sit thereby

preventing the activation of complement.

Surface proteins

Collagenase and hyaluronidas: Which degrade collagen and hyaluronic acid thereby

allow bacteria to spread through subcutaneous tissue they are especially important in

cellulitis casued by Streptococcus pyogenes .

Enzymes secreted by invasive bacteria

Coagulase: Which is produced by staphylococcus aureus and accelerates theformation of a fibrin clot from its precursor fibrinogen (this clot may protectthe bacteria from phagocytosis)by coating the organisms with a layer of fibrin.

Coagulase test: Coagulase is an enzyme that causes a clot to form when bacteria areincubated with plasma .The test is used to differentiate Staphylococcus aureus (coagulasepositive) from coagulase-negative staphylococci S. epidermidis and S. saprophyticus

– Invasion

• e.g. Strep pyogenes pharyngitis

– Migration

• e.g. Escherichia coli urinary tract infection

– Innoculation

• e.g. Coagulase negative staphylococcus prosthetic joint

infection

– Haematogenous

• e.g. viridans Strep endocarditis

What is a surface? Objective 4Interface between a solid and either a liquid or gas.

Patient

Pathogen

Infection Management Outcome

Mechanism of infection

epithelium

hair

nails

conjunctival

gastrointestinal

respiratory

genitourinary

• External • Internal

– Cellulitis – Endovascular

– Pharyngitis – Endocarditis

– Conjunctivitis – Vasculitis

– Gastroenteritis – Septic arthritis

– Urinary tract infection – Osteomyelitis

– Pneumonia – Empyema

Intravascular lines

Peritoneal dialysis

catheters

Prosthetic joints

Pacing wires

Cardiac valves

Endovascular grafts

Ventriculo-peritoneal shunts

Prosthetic valve endocarditis

HACEK group: Haemophilus, Aggregatibacter, Cardiobacterium, Eiknenella, Kingella

Prosthetic joint infections

Cardiac pacing wire endocarditis

Processes in the pathogenesis of infection at surfaces

Objective 5

• Adherence to host cells or prosthetic surface

• Biofilm formation

• Invasion and multiplication

• Host response

– Pyogenic (neutrophils -> pus)

– Granulomatous (fibroblasts, lymphocytes,

macrophages -> nodular inflammatory

lesions)

What is Biofilm

Biofilms are multicellular aggregates of bacteria and yeast

that congregate on surfaces.

Biofilm formation is a nearly universal bacterial trait, and

biofilms are found on almost all natural and artificial

surfaces

Biofilms are formed to protect the bacteria from host

defenses, antibiotics, and from harsh environmental

conditions.

Some examples of biofilms are the plaque that forms on

teeth and the slime that forms on surfaces in watery areas

A process that enables bacteria to

communicate using secreted signaling

molecules called auto inducers

This process enables a population of

bacteria to regulate gene expression

collectively and therefore, control behavior

on a community-wide scale.

Quorum Sensing helps in

Bacteria use Quorum sensing to

mastermind behaviors or (Controls)

– Sporulation

– Biofilm formation

– Virulence factor secretion

Three principles steps

1) production of small biochemical signal molecules by the bacterial cell.

2) release of the signal molecules, either actively or passively, into the surrounding

environment

3) recognition of the signal molecules by specific receptors once they exceed a

threshold concentration, leading to Gene expression ->co-operative behaviours and

more production.

Natural surface

• Maintain surface integrity

• Prevent bacterial surface colonisation

• Remove colonising bacteria

Prosthetic surfaces

• Prevent contamination

• Inhibit surface colonisation

• Remove colonising bacteria

Question

A-Pseudomembrane colitis is caused by the strains of which of the following microorganism?

1-Streptococcus mutant

2-Clostridium difficile

3-Streptococcus saprophyticus

4- Clostridium botulinum

B- Where does the Streptococcus mutants adhere to the body site

1- intestinal tract

2-tongue

3-teeth

4-hairs