PATHOGENESIS OF BACTERIAL INFECTIONS

THE ATTRIBUTES OF MICROBIAL PATHOGENS

Joanna Kdzielska Depatment of Medical Microbiology Medical University of Warsaw, Warsaw, Poland

PATHOGENESIS OF BACTERIAL INFECTION

HOST-PARASITE INTERACTIONS
Pathogen microbe that can cause

disease in a susceptible host

Opportunistic Pathogen microbe

that can cause disease only if a significant change occurs in host resistance or within the organism itself

HOST-PARASITE INTERACTIONS
Opportunistic Infections - infections

caused by opportunistic pathogens

Iatrogenic Infections infections

resulting from medical treatment or procedures

HOST-PARASITE INTERACTIONS
Virulence relative ability of a

microorganism to cause disease, or the degree of pathogenicity

Virulence factors factors such as

capsules, toxins, enzymes, cell wall receptors, pili, etc. that allow pathogens to evade or overcome host defenses

HOST-PARASITE INTERACTIONS
Infectious Agent Factors Adherence most infectious agents must attach to host cells before infection occurs Proliferation pathogens must be able to replicate after attachment to host cells (overcome host resistance factors) Tissue Damage makes the infection visible; results from toxins or from host inflammatory substances

BACTERIAL VIRULENCE FACTORS

GRAM- POSITIVE: Peptidoglycan Surface proteins Capsule Exotoxins Spores

BACTERIAL VIRULENCE FACTORS

Gram- negative: LPS Pili (Fimbriae) OMP Capsule Exotoxins Flagella Siderophore system

CELL WALL COMPONENTS

PEPTIDOGLYCAN & L P S:

Pyrogenic acute phase response

L P S:

also inflamatory response

ENDOTOXIN
(LPS = LIPOPOLISACCHARIDE) OF GRAM-NEGATIVE BACTERIA

Ecthyma gangrenosum

SURFACE PROTEINS OF GRAM-POSITIVE BACTERIA

ADHERENCE
S.aureus, S.pyogenes

ANTIPHAGOCYTIC
Proteins: A- S.aureus, M & M-like S.pyogenes

ANTIGENIC SHIFT
S.pyogenes

FIMBRIAE / PILI OF GRAMNEGATIVE BACTERIA

p p All Gram (-) Several hundreds /cell p Different types: CFA P fimbriae S fimbriae Role: attachment colonization stage of infection

FIMBRIAE OF E. COLI

E. COLI FIMBRIAE

FIMBRIAE / PILI FOR ADHESION

OUTER MEMBRANE PROTEINS (OMP) OF GRAMNEGATIVE BACTERIA

Yersinia resist phagocytic killing

YOPs: Yop H Yop J/P Yop E Yop N/M

GRAMGRAM-NEGATIVE CELL WALL

CAPSULE
PREVENTS PHAGOCYTOSIS POLYSACCHARIDE GRAM-POSITIVE &

GRAM-NEGATIVE BACTERIA

BACTEROIDES FRAGILIS
CAPSULE

FUZZY COAT OF STREPTOCOCCUS PYOGENES

ENCAPSULATED GRAMPOSITIVE BACTERIA

S.pyogenes S.agalactiae S.aureus Bacillus anthracis
(HYALURONIC)

S.pneumoniae

ENCAPSULATED GRAMNEGATIVE BACTERIA

Klebsiella pneumoniae E.coli Yersinia pestis Haemophilus influenzae Pseudomonas aeruginosa Neisseria sp. Bacteroides fragilis

EXOTOXINS
Toxic bacterial proteins Most plasmid or phage coded Gram-positive & Gram-

negative bacteria

BACTERIAL EXOTOXINS
A /B type Superantigens Cytolytic enzymes

A /B TOXINS
Dimeric structure Biochemical targets:

2 ribosomes 2 transport mechanism 2 intracellular signals

(cAMP, cGMP)

A /B TOXINS

EFFECTS OF A/B TOXINS

DIARRHOEA Enterotoxins of E.coli, Vibrio, Salmonella LOSS OF NEURONAL FUNCTION Clostridia:C.tetani, C.botulinum DEATH C.diphtheriae, P.aeruginosa, E.coli-EHEC

EXOTOXINS & ENDOTOXINS

Exotoxins
Most have two units, one for attachment and the other is the toxin Commonly coded by phages or plasmids

Endotoxins
G- bacteria Toxicity caused by the lipid A portion of the lipopolysaccharide in the cell wall Cause dramatic host responses, including inflammation, fever, hypotension, septic shock, death

Toxin

Receptor

Endocytic

Target

Effect

Diptheria phage

Heparin binding epidermal growth factor

Elongation factor 2 Ribosylation

Inhibition of protein synthesis - mycocardial cells especially susceptible Inhibits release of acetyl choline. No stimulation flaccid paralysis Inhibits release of gamma-amino butyrate. No inhibition of action - spastic paralysis C-AMP rises. NaCl lost water from blood. Diarrhoea - 40L per day C-AMP as in cholera. Mucous secretion ?cough

Botulinum phage plasmid

Peripheral nerves glycoprotein

Synaptobrevins (synaptic vesicles) Zincdependent endoeptidase

Tetanus

Central nerves

Synaptobrevins

Cholera phage

GMI gangliosides

Pore?

G-proteins ribosylation

Pertussis

Lactosyl

G-proteins ribosylation

SUPERANTIGENS

Stimulation of T- cell receptors & MHC II

Staphylococcal enterotoxins TSST-1 S.aureus SPES S.pyogenes

SUPERANTIGENS

Superantigens are molecules which short-circuit the immune system, resulting in massive activation of T-cells rather than the usual, carefully controlled response to foreign antigens. It is believed that they do this by binding to both the variable region of the -chain of the T-cell receptor (V-) and to MHC II molecules, cross-linking them in a non-specific way

FLAGELLA OF GRAMNEGATIVE BACTERIA

1 Most Gram(-) 1 Role: motility
no flagella: Salmonella gallinarum Shigella Klebsiella sp.

BACTERIAL FLAGELLA

FLAGELLA OF SALMONELLA

PROTEUS MIRABILIS

FLAGELLA OF SPIROCHAETA

SPIROCHAETA

CAMPYLOBACTER

SIDEROPHORE SYSTEM OF GRAM-NEGATIVE BACTERIA

AEROBACTIN PIGMENTS of Pseudomonas aeruginosa Role:

iron acquisition

PSEUDOMONAS AERUGINOSA

BACTERIAL BIOFILM
Regulation of ica operon expression in Staphylococcus epidermidis. The icaADBC gene cluster encodes a poly-saccharide adhesin required for biofilm formation. The icaR gene encodes a represor protein which impairs expresion of the ica genes and biofilm formation. The activity of icaR is in turn influenced by environmental conditions.

Widespread use of implanted biomaterials such as catheters used for renal dialysis in hospital patients has resulted in new risks of infection

GRAM-POSITIVE BACTERIA: SPORES

Bacillus Clostridium

Spores of Clostridium botulinum

DEGRADATIVE ENZYMES OF BACTERIA

Hyaluronidase Protease DNA-se Elastase Collagenase Coagulase Catalase Lipase

IMMUNE RESPONSE

INHIBITION OF FAGOLYSOSOME FUSION

LEGIONELLA MYCOBACTERIUM TUBERCULOSIS MYCOBACTERIUM LEPRAE LISTERIA CHLAMYDIA species

Legionella pneumophila

LISTERIA

THE CLONAL NATURE OF BACTERIA GENETIC MATERIAL

Plasmids IS sequencies Phages

BACTERIAL VIRULENCE FACTORS

BACTERIAL GENETIC EXCHANGE

HOST-PARASITE INTERACTIONS
Host Resistance Factors Physical barriers skin Cleansing mechanisms
Desquamation Fluids of the eye (IgA and lysozyme) Respiratory, digestive, urinary, and genital tracts have fluids and movements to cleanse the surfaces

FIMBRIAE / PILI FOR ADHESION

HOST-PARASITE INTERACTIONS
Antimicrobial Substances
Lysozymes Antibodies -lysins Interferon

Indigenous Microbial Flora Phagocytosis Chemotaxis Inflammation Immune Responses

HOST-PARASITE INTERACTIONS

White blood cell eating bacteria

HOST-PARASITE INTERACTIONS
Invasion all pathogens have the ability to penetrate and grow in tissues Dissemination
Spread of organisms to distant sites Some pathogens stay at site (C. diphtheriae); others spread (Salmonella ssp.)