Bacteria Pathogenicity

Ability to Cause Infection

Infectious Diseases

• Encounter-bug meets host (reservoir)

• Bug adheres to host

• Entry-bug enters host

• Multiplication- bug multiplies in host–

Infectious Diseases

• Damage to host– Virulence of bug or host response

• Outcome- bug or host wins or

• Coexist- chronic infection

Reservoir

• Exposure to microbe– Humans– Animals – Environment

Virulence Factors

• Enhance colonization & growth

• # of cells required to establish infection

• Measure of pathogenicity

Adherence (Virulence Factor)

• Attachment to host cells

• Adhesins on pathogen (proteins)– Bind to complimentary surface receptor

Adherence

• Prevent infection

• Influenza changes adhesions over time

• Neisseria gonorrhoeae -variety of adhesions

Portals of Entry

• Mucous membranes– Respiratory

– GI– Genitourinary

• Conjunctiva

Portals of Entry

• Skin

• Bugs have preferred portal

• C. tetani spores in soil --- anaerobic wound

Inoculum

• Number of microbes-dose

• Greater dose, more chance infection will occur

• ID50 or LD50 expresses virulence

– Infectious or lethal dose for 50% of population

– LD50 used for toxins

ID50

• ID50 for B.anthracis via skin is 10 to 50 endospores

• Via which route is infection more likely?

• Via which route is infection more lethal?

Invasins

• Adherence of microbe to surface

• Activates factors that let microbe in-penetration

• Microbes produce invasins (proteins)

• Endocytosis

Colonization

• Requires multiplication

• Compete with normal flora for space & nutrients

Colonization

• Overcome local host defenses– IgA (mucosal surfaces)

• Avoid IgA– Rapid turnover of fimbriae/pili– Antigenic variation in type of pili– IgA proteases (enzymes) destroy IgA

Multiplication

• Need Fe to multiply– Most is bound in host– Have own iron-binding molecules that compete

for Fe-siderophores• \

Avoid Phagocytosis

• Avoid recognition & attachment

• Capsule– Impairs phagocytosis DT negative charges– Produce antibodies to capsule– \

Avoiding Phagocytosis

• Components of cell wall –virulence

– Mycolic acids in M. tuberculosis

Surviving Within Phagocyte

• Escape from phagosome, vesicle, before

fuses with lysosome

• Prevent fusion with lysosome

• Grow inside phagocyte protected from host

Tuberculosis

• Ancient disease

• 1/3 of world population infected

• 8 million develop active TB each year

• 2 million die each year

• AIDs increases activation of latent TB

Tuberculosis

• Dependent upon virulence of strain & host resistance

• Produces cell mediated immunity which prevents active disease in many people

• Multi drug resistance has developed

S & S of Pulmonary TB

• Chronic disease

• Progressive weight loss

• Night sweats

• Chronic cough

• Hemoptysis

Mycobacterium tuberculosis

• Acid fast bacillus (AFB)

• Resistant to drying

• Aerobic, slow growth

• Airborne transmission

Mycobacterium tuberculosis

• Inhale airborne droplets

• Ingested by alveolar macrophages

• Multiply in macrophages even with ongoing immune response

TB Response

• Host immune response-delayed type hypersensitivity reaction

• Tissue damage DT Inflammatory response

TB Conversion

• TST skin reaction is positive

• Occurs within 24 – 48 hours after exposure to TB antigens

• Purified protein derivative of bacillus

• Cell mediated immunity

• Sensitized T cells react with proteins

QuantiferonGold

• Blood test

• Detects interferon gamma

How to Confirm Diagnosis

• Sputum cultures for AFB smear & culture

• Chest xray

Pathogenesis

• LTBI (latent TB infection)– Immune defenses contain organism– Formation of tubercle – TB converter– No S&S of disease

Active Disease

• Low resistance – Disease not controlled– Cytokines damage lung– Acute pulmonary infection– Can spread & cause death

TB Outcomes

• Primary infection- positive skin test– 90% immune system controls infection via

cellular immunity• TB germs isolated within tubercles( Activated

macrophages)

TB Outcomes

• 10% progressive primary infection-not controlled– Illness or death if not treated– Cavities in lungs– Spread throughout body

Secondary or Reactivation Infection

• Reinfection-2nd exposure or

• Bacteria escape immune system-reactivation

• Activated macrophages release cytokines

• Delayed hypersensitivity reaction

Prevention of Transmission

• Negative pressure rooms

• Respirator masks-fit tested

• Admit staff aware of symptoms of TB

• Yearly TST of staff

• Conversions treated with 6-9 months of INH

Treatment

• INH for LTBI or TB conversion

• TB disease-active TB– 4 drugs till drug sensitivities return– DOT

• 9- 12 months of treatment– Slow growing– Impedes abx entering cell wall

Resistant TB

• MDR TB– Resistant to INH, & 1 other TB drug

• XDR TB– Resistant to all 1st line drugs– Use 2nd line drugs for several years– Often leads to death

• DT improper treatment

BCG

• Live culture of M. bovis– Attenuated strain– Used in other countries to protect children from

miliary disease– Can cause positive reaction on TST

Latent vs Active

• Latent TB– Infected but no S&S– Not infectious

• Active TB– S&S of disease– Infectious if pulmonary TB

Leprosy

• Hanson’s disease- discovered in 1873

• Seen in tropics and underserved countries

• U.S.-150 new cases per year

Leprosy

• Infection of nervous system

• Infects the peripheral nerves within skin

• 2 forms of disease dependent upon immune response

M. leprae

• Tuberculoid form– Regions of skin, lost sensation surrounded by

nodules– Lose pigmentation– Causes strong cell mediated response– Activated macrophages keep microbe under

control

Lepromatous Form

• Weak immune response & microbe spreads

• Skin & nerve cells infected

• Shed large #s in nasal secretions and oozing sores-more infectious

Invasion via Enzymes

• Exoenzymes- excreted to outside

• Coagulases-clot fibrinogen in blood

Kinases

• Breakdown fibrin– Produced by strep– Invades tissues & spreads– Used to isolate infections

Enzymes

• Hyaluronidases – hydrolyzes hyaluronic acid (polysaccharide)

• IgA proteases– Destroys IgA antibodies in secretions

Enzymes

• Leukocidins– Kill neutrophils

• Hemolysins-staph & strep– Dissolve RBCs– Able to obtain Fe

Invasion via Toxins

• Toxins– Poisonous substances damage tissues– Cause shock, fever, inhibit protein synthesis

• Two types– Exotoxins– Endotoxins

Exotoxins

• Produced inside cell

• Mostly proteins, kill in low concentrations

• Mainly gram positive

• Gene on plasmids or phages– Not bacterial genes

Exotoxins

• Destroy part of cell or inhibit metabolic processes– Specific for each exotoxin

• Toxin responsible for S &S of disease

Exotoxins

• Antitoxins– Antibodies to toxin

• Toxoid– Inactivated exotoxin– Use to induce immunity to toxins– Vaccines

A-B Toxins

• 2 parts-polypeptides

• A-active or enzyme component

• B-binding component

• B binds toxin to host cell

• A-B toxin enters

• Components separate & A kills host– Disrupts protein synthesis

Superantigens

• Bacterial toxins provoke intense response

• Stimulate nonspecifically T cells

• T cells release cytokines– Fever, N & V, diarrhea

– System wide effect with organ failure

Naming of Exotoxins

• Neurotoxins attack nerve cells

• Cardiotoxins-heart cells

• Hepatoxins-liver cells

• Leukotoxins-WBCs

• Enterotoxins-release of fluids-nausea, vomiting & diarrhea

• Cytotoxins-variety of cells

Endotoxin

• Lipid A

• Stimulates macrophages to release cytokines– High levels are toxic

• Activate complement & immune defenses

S & S

• Chills, fever, weakness, aches

• Later shock and death

• Activate blood clotting– Clots obstruct capillaries– Death of tissues-DIC

• Endotoxin shock sepsis

Shock

• Loss of blood pressure

• Gram negatives-endotoxin shock

• Cytokine-tumor necrosis factor (TNF)

• Damages blood vessels -leaky

Endotoxins

• Do not promote antitoxins ( abs to Lipid A)

• Antibodies produced to bug don’t affect toxin

• Assay to detect minute amounts of endotoxins in drugs & body fluids

Staphylococci

• Staph divided based upon coagulase

• S. aureus is coagulase positive

• S. epidermidis (CNS)

• Found on humans and animals

S. aureus

• Named for yellow pigmented colonies

• Facultative anaerobe, catalase positive

• Grows well in nares-colonization

S. aureus

• If infected, shed high numbers– Don’t work around food or patients

• Survives well in environment-resists drying

• Now resistant to most antibiotics

• MRSA

Epidemiology

• Nasal carriers have 2-7 times greater risk of infection than non carriers

• Screening of high risk pts

Successful Pathogen

• Biofilm

• Capsule

• Exoenzymes

• Toxins

Biofilm

• Protective growth medium for microorganisms– WBCs, antibodies, antibiotics

• ET & trach tubes-PNA

• IV catheters-BSIs

• Implants- SSIs

• Facilitates transfer of resistant genes

Capsule

• Protection from phagocytes

• Attachment

• Prevents dehydration

Enzymes

• Proteases– Degrade fibrous protein in collagen

• Hyaluronidase– Degrades cement between cells

• Promote spread in tissues

Enzymes

• Lipases– Colonize hair follicles– Breaks down sebum

• Leukocidins– Kill WBCs– Pus formation (pyogenic)

Skin Infections

• Pimples, boils, abscesses– Impetigo of newborn, blisters– Infection of insect bites, burns, scrapes etc.

• Cellulitis– Spread of bug through skin and soft tissue

• Wound infections-major cause • Use of antibiotics• Resistant MRSA

Invasion via Toxins

• Produce many exotoxins

• Secreted to outside– Increase ability to invade tissue and cause

damage

• Exfoliatin toxin-scalded skin syndrome– Occurs in infants

Toxic shock syndrome

• Superantigen

• Symptoms – High fever, hypotension, vomiting, rash &

death

• Female normal flora– Use of tampons abrade wall

S. aureus Intoxication

• Enterotoxin causes food poisoning– Restricted to GI tract

• S & S       – Vomiting, diarrhea, abdominal cramps

• Prevention-hand hygiene & refrigerate food – Toxin not produced

Treatment

• Use of antibiotics for infections only

• Over use/misuse

• Resulted in selection of MRSA in hospitals

• Isolate these patients

CA-MRSA

• MRSA in community

• Patient lacks risk factors for HA-MRSA– Hospitalization– Surgery– Long term care– Dialysis– Indwelling catheters

Outbreaks in Community

• Sports participants

• Daycare, elementary schools

• Inmates

• Military recruits

• Men having sex with men (MSM)

• Tattoo recipients

CA-MRSA

• Susceptible to more antibiotics

• Gene for Panton-Valentine leukocidin (PVL)

• Causes skin & soft tissue infections

PVL Gene

• May be associated with severe necrotizing infections

• HA MRSA & S. aureus strains rarely carry this gene

Preventing Transmission• Exclude from work, school, sports, etc.

• Dispose of used bandages in trash

• Avoid sharing personal items

• Shower every day with Dial or anti-bacterial soap

Clostridium botulinum

• Gram positive rod

• Soil and vegetation

• Produces several exotoxins- neurotoxin

Neurotoxin

• Toxin causes flaccid paralysis of muscles

• Prevents release of neurotransmitter, acetylcholine– Muscles can’t contract

Botulism-Foodborne Disease

• Disease caused by exposure to toxin– Microbe can’t compete with normal gut flora in adults

• Infant botulism-don’t have protective gut flora– Associated with honey

• Treatment-supportive care– Ventilator

– Antitoxins-trivalent

Toxin

• 1 pt kills everyone in world• 1 oz kills everyone in US• Botox –type A

Clostridium tetani

• Gram positive, endospore forming rod

• Found in soil contaminated with animal feces

• Encounter- deep puncture wounds with dirt

Neurotoxin

• Released by lysis of bacteria

• Binds to nerve cells that control contraction of skeletal muscles

• Toxin blocks relaxing pathway so both muscles contract spasm

• Jaw muscles first, can’t open mouth

Lockjaw

• Death from spasms of respiratory tract– Pneumonia & regurgitation of stomach contents

• Prevention– DPT -toxoid, inactivated toxin– Anti toxin neutralizes toxin

Clostridium difficile

• Anaerobe

• Endospore forming rod

• Vegetative cells– Survive for at least 24 hr on inanimate surfaces

Epidemiology

• Present in soil and water

• Found in gut of humans & animals

• Hospitals are a major reservoir– 20-40% of pts become colonized

• Recently, found in pork

Range of Disease

• Asymptomatic carriage ( outnumber those with disease)

• Clostridium difficile infection (CDI)

• Pseudomembranous colitis

• Toxic megacolon

• Sepsis

• Death

Pathogenesis of CDI

• C. difficile ingested either as vegetative form or spores

• Spores germinate in small intestine • Normal flora disrupted by antibiotic

therapy, disease can occur• C. difficile releases toxins causing severe

inflammation of colon

New Issues

• CDI rates are increasing

• Epidemic strain found in US, Canada, & Europe

• More severe disease– Higher mortality– Higher rates of colectomy

Treatment

• Stop the inciting antibiotics• 25% recover without further treatment• Flagyl is first line of therapy

Treatment

• Must monitor response to therapy

• Vanco po for moderate to severe disease

• Both antibiotics disrupt the normal flora– Susceptible to relapses or re-infection

Transmission

• Fecal-oral route

• Contaminated hands of HCWs

• Contaminated hands of patients

• Contaminated environment

Environment

• Clean and disinfect surfaces in close proximity of the patient

• Patient care equipment.

• Use bleach for C. difficile

• Privacy drapes