Virulence, Adherence, & Antigenic Diversity

INITIAL PATHOGEN-HOST INTERACTIONS Host must make contact with its environment exchange air ingest food eliminate waste HOST DILEMMA PREVENTION OF MICROBIAL ENTRY VS CONTACT WITH ENVIRONMENT

PATHOGENS CAPITALIZE ON POINTS OF ENTRY DIGESTIVE TRACT RESPIRATORY TRACT UROGENITAL TRACT CONJUNCTIVA HOST POSSESSES DEFENSE MECHANISMS TO PREVENT ENTRY MECHANICAL CLEANSING e.g. blinking & peristalsis

pilC pilE opa capsule opc Adherence Adherence Invasion Serum resistance Adherence Invasion

a bacterial defense against host’s mechanical cleansing ADHERENCE a bacterial defense against host’s mechanical cleansing HOST CELL RECEPTOR bacterium BACTERIAL ADHESIN PILI OMPs host cell requires two factors host receptor bacterial adhesin

surface protein structure ADHESIN surface protein structure 1) pilus (fimbria) - for attachment at a distance 2) non-fimbrial adhesin (outer membrane protein) - for intimate attachment

pili flagella www.nature.com/genomics/images/e_coli_200.jpg

ADHESIN DIVERSITY HOST RANGE ENVIRONMENTAL CONDITIONS SPECIFIC ADHESIN FOR SPECIFIC HOST RECEPTOR ex. N. GONORRHEA (VAGINA vs RECTUM) ENVIRONMENTAL CONDITIONS ex. Uropathogenic E. COLI (PYELONEPHRITIS ISOLATES) EXPRESS TYPE 1 PILI – (Bladder) LIQUID TYPE P PILI – (Kidney) SOLID SURFACE

VARYING ADHESIN COMPOSITION ADHESIN DIVERSITY MEDICAL IMPORTANCE NEISSERIA GONORRHEA AVOID IMMUNE SYSTEM BY VARYING ADHESIN COMPOSITION

Majority with one antigen Minority with different antigen

majority killed by immune response subpopulation avoids immune response

Subpopulation multiplies New subpopulation

ANTIGENIC VARIATION

MECHANISMS OF ANTIGENIC VARIATION each N. gonorrhea cell possesses genetic information for a large number of variant pilin proteins thus, each cell can produce progeny that synthesize pili that exhibit different epitopes than did its parent

} PILIN GENE ORGANIZATION pilE pilS pilE - expressed due to promoter pilS - silent genes due to i) lack of promoter ii) incomplete pilS genes same orientation as pilE } A B C A promoter pilE pilS

upon the sequence of pilE Antigenicity depends upon the sequence of pilE } A A B C A } pilS pilE B A B C B

MECHANISMS i) gene conversion ii) transformation

Gene Conversion pilS = endogenote A B C A type A pilus A B C type B pilus recombination

Transformation Lysed Donor Recipient pilS = exogenote B A C recombination A B C C Recipient type C pilus

Antigenic possibilities are infinite D X X B B/C B/C B/C/D