Pathogenesis of Bacterial Pathogenesis of Bacterial Infections

Sofyan LubisDepartemen Mikrobiologi FK USUMedan

Patogenisitas & Virulensi :Patogenisitas & Virulensi :

Th t l t d t t There are two related terms to characterize the disease-related capabilities :capabilities :

PATHOGENICITYPATHOGENICITYVIRULENCE

PATHOGENICITY & VIRULENCE

Pathogenicity refer to ability of Pathogenicity refer to ability of a microorganisms to cause disease.

Virulence refer to the degree of pathogenicity pathogenicity In other words :Virulence is the relative ability of Virulence is the relative ability of a pathogen to infect a host and cause diseasecause disease

Virulence factors of Infectious Agents:Agents:

Adh i f t ( dh t h t Adhesion factors ( adhere to host cells)E t ll l Extracellular enzymesToxins : exotoxins & endotoxinsAntiphagocytic factors :

capsules & antiphagocytic chemicals

The Role of Adhesion in InfectionThe Role of Adhesion in Infection

L i Obj ti Learning Objectives :

1. List the types of adhesion factors and the roles they play in infection

2. Explain how a biofilm may facilitate contamination and infection

Adhesion ( attaching to the Host )Adhesion ( attaching to the Host )

Adhesion is a process by which Adhesion is a process by which microbes gain a more stable foothold at the portal of entryat the portal of entryAdhesion is dependent on binding between specific molecules on both pthe host and pathogen, thereby a particular pathogen is limited to onlythose cells ( and organisms) to which those cells ( and organisms) to which it can bind

KOLONISASI BAKTERI DI JARINGAN TUBUH MANUSIAJARINGAN TUBUH MANUSIA

Bakteri Jaringan ( tissue)Bakteri Jaringan ( tissue)N.gonorrhoeae Epitel saluran kemihStrep mutans Permukaan gigiStrep.mutans Permukaan gigiStrep,salivarius Permukaan lidahVibrio cholerae Epitel usus halusVibrio cholerae Epitel usus halusE.coli Epitel usushalusStaph aureus Mukosa hidungStaph.aureus Mukosa hidungStaph.epidermidis Permukaan kulitC diphtheriae ThroatC.diphtheriae Throat

AdhesionAdhesion……

Pathogens such as bacteria fungi Pathogens such as bacteria, fungi attach most often by mechanisms:

Fimbriae ( pili)Fimbriae ( pili)Surface proteins,andAdhesive slimes or capsules

h hFirm attachment to host tissues is almost always a prerequisite for causing disease since the body has causing disease since the body has so many mechanism for flushing microbes from its tissues

Specific Adherence

Adherence (of the bacterium to the eukaryotic cell surface) is inhibited by :cell surface) is inhibited by :

a. isolated adhesin or receptor moleculesa. isolated adhesin or receptor moleculesb. adhesin or receptor analogsc. enzymes and chemicals that specifically c e y es a d c e ca s t at spec ca y

destroy adhesins or receptorsd. antibodies specific to surface d a bod es spec c o su ace

components (i.e. adhesins or receptors

Extracellular enzymesExtracellular enzymes

Many pathogens secrete enzymes that Many pathogens secrete enzymes that enable them :

To dissolve structutal chemicals in the body and thereby maintain an infection, invade and thereby maintain an infection, invade further, and avoid body defenses

Some extracellular enzymes are :o a u a y aHyaluronidase CollagenaseCoagulasegKinasesKeratinase & mucinase

Extracellular enzymes :

Hyaluronidase digests hyaluronic Hyaluronidase digests hyaluronic acid, the ground substance that cements animal cells together g(“glue”).Collagenase digests the principal g g p pfiber of connective tissue and is an invasive factor of Clostridium sp.

Keratinase : digests the principal Keratinase : digests the principal component of skin and hair .This enzyme is secreted by fungi that enzyme is secreted by fungi that cause dermatophytosis ( ringworm, tinea ).Mucinase : digests the protective coating on mucous membranes. ( Mucinase is a factor in amoebic ( Mucinase is a factor in amoebic dysentery ).

Extracellular enzymes:y

C l hCoagulase :an enzyme that causes clotting of blood or plasma, providing a “hidden place” for bacteria within l ta clot.

Kinases: such as staphylokinase & Kinases: such as staphylokinase & streptokinase digest blood clots (dissolving fibrin clots) allowing subsequent invasion of damaged subseque t as o o da agedtissues

Hyaluronidase Degrades hyaluronic of connective Hyaluronidase Degrades hyaluronic of connective tissue

Collagenases Dissolve collagen framework of muscles

Neuramidases Degrades neuraminic acid of intestinal mucous

Coagulase Converts fibrinogen to fibrin which causes clotting

Kinases Converts plaminogen to fibrin which digest fibrin

Leukocidin Disrupts neutrophil membranes and causes discharge of lysosomal granules

Streptolysins Repels phagocytes & disrupts phagocyte membrane and causes discharge of lysosomal granules

Toxins :Toxins are chemicals produced by p ypathogens that either harm tissues or trigger host immune responses that cause diseasedisease.

WHAT IS THE DISTINCTION BETWEEN EXTRACELLULAR ENZYMES AND TOXINS ? The distinction is not always clear,because many enzymes are toxic, and many toxins y y , yhave enzymatic action

Two types of toxin:Two types of toxin:

EXOTOXINS

ENDOTOXIN

ExotoxinsExotoxins

E t i t i ith t Exotoxins are proteins with a strong specificity for a target cell and extremely powerful effectsextremely powerful effects.Exotoxins generally affect cell by :

Damaging the cell memb ane and Damaging the cell membrane and initiating lysis, orDisrupting intracellular functionp g

EXOTOXINS:EXOTOXINS:

E t i t d b iExotoxins secreted by many micro-organisms are central for their pathogenicitiespathogenicities.

Th i i l f iThree principals types of exotoxins:CytotoxinsNeurotoxinsNeurotoxinsEnterotoxins

Types of Exotoxins :Types of Exotoxins :

C t t i hi h kill h t ll i Cytotoxins which kill host cells in general or affect their function.

Neurotoxins,which specifically i f i h ll f iinterfere with nerve cell function

Enterotoxins,which affect cells lining the gastrointestinal tract

Bacteria that secrete exotoxins:Bacteria that secrete exotoxins:

Clostridium perfringens ( Cl.welchii )Clostridium botulinumClostridium tetaniCorynebacterium diphtheriaeCorynebacterium diphtheriaeS.aureus that cause food poisoningStrains E coli that cause diarrheaStrains E.coli that cause diarrhea

EndotoxinEndotoxin

Endotoxin is actually a chemical called LPS Endotoxin is actually a chemical called LPS, which is part of the outer membrane of gram-negative cell wall

Endotoxin is released only when bacterial cells die naturally or are digested by phagocytic cells, such as macrophages. These LPS cells, such as macrophages. These LPS molecules are released into the infection site or into the circulation.

Endotoxin can cause fever, inflammation, diarrhea,hemorrhage, shock, and blood coagulationg

Endotoxin :Endotoxin :

Most Gram negative pathogens can Most Gram-negative pathogens can potentially life threatening because the release of endotoxin from dead bacteria can produce serious, systemic effects in the hostBl d i f ti b S l ll Blood infection by Salmonella, Shigella, N.meningitidis,and E.coli are particularly dangerous in that it can particularly dangerous in that it can lead to fatal endotoxic shock.

Antiphagocytic factorsAntiphagocytic factors

The longer a pathogen remains in a host The longer a pathogen remains in a host, the greater the damage and the more severe the disease.To limit the extent and duration of infections, the body’s phagocytic cells such as macrophages,engulf and remove invading pathogens.Two virulence factors related to the Two virulence factors related to the evasion of phagocytosis are bacterial capsules and antiphagocytic chemicals.p p g y

Bacterial CapsulesBacterial Capsules

The capsules of many pathogenic bacteria The capsules of many pathogenic bacteria are effective virulence factors because

Many capsules are composed of chemicals that y p pare normally found in the body, as a result they do not stimulate the host’s immune response.p

Capsules are often slippery,making it diffi lt f h t t d d difficult for phagocytes to surround and phagocytize them

Antiphagocytic chemicals ;p g y ;

Some bacteria produce chemicals that Some bacteria produce chemicals that prevents the fusion of lysosomes with phagocytic vesicles (phagosome) which ll th b t i t i i id allows the bacteria to survive inside

phagocytes ( e.g. gonococcus).S.pyogenes produces a protein on its cell S.pyogenes produces a protein on its cell wall and fimbriae,called M.protein,that resists phagocytosis and thus increases virulencevirulence.Bacteria that produce leukocidins which capable of destroying phagocytic cells.p y g p g y

Virulence Factors ( summary)Virulence Factors ( summary)

1 E t ll 1. Extracelluar enzymes.1. Hyaluronidase and collagenase digest

structural materials in the body.structural materials in the body.

2. Coagulase in effect “camouflages”bacteria inside a blood clot,whereas kinases digest clots to release bacteria.

Virulence Factors ( summary)

2 T i2. Toxins:Exotoxins are released from living

th d h i hb i pathogens and harm neighboring cells.E d i i l d f Endotoxin is released from many dead Gram-negative bacteria and can trigger widespread disruption of can trigger widespread disruption of normal bodily functions

Virulence Factors : summaryVirulence Factors : summary

3 A ti h ti f t3. Antiphagocytic factors:1. Bacterial capsules can prevent phago-

cytosis or stop digestion by a phagocyte.cytosis or stop digestion by a phagocyte.2. Antiphagocytic Chemicals:

1. Chemical substances that prevent the f i f l ith h ti fusion of lysosomes with phagocytic vesicles( phagosome)

2. A protein on the cell wall and fimbriae ( ll d M t i ) i S(called M.protein) in S.pyogenes.

3. Leukocidins which capable of destroying phagocytic cells.

Steps in PathogenesisSteps in Pathogenesis

1 Pathogen enters Host1. Pathogen enters Host2. Pathogen clonizes appropriate site3. Pathogen reproduces rapidly3. Pathogen reproduces rapidly4. Prodromal signs may appear5. Acute signs present6. Decreased reproduction & death of

pathogensb d7. Recovery – signs subside

8. Total recovery

Development of Infection: Clinical Signs and Symptoms

Local signsLocal signsInflammationPurulent exudate if bacterial infection; Purulent exudate if bacterial infection; serous exudate if viralTissue necrosisLymphadenopathyRespiratory effects

S i iSystemic signsFever, fatigue, headache, nausea