Age-related differences in rabbits during experimental Staphylococcus aureus keratitis.
OBJECTIVE
To analyze age-related changes in susceptibility to experimental Staphylococcus aureus keratitis and purified alpha-toxin in rabbits.


METHODS
Intrastromal injection of S. aureus (100 colony-forming units [CFUs]) induced keratitis in young (6-8 weeks) and aged (approximately 30 months) New Zealand White rabbits. Bacteria and polymorphonuclear leukocytes (PMNs) per cornea were quantified. Purified alpha-toxin at 1, 10, 25, or 50 hemolytic units (HU) or heat-inactivated alpha-toxin was intrastromally injected into corneas, and pathologic changes were determined by slit lamp examination (SLE) and histopathologic analysis. alpha-Toxin hemolysis assays were performed using erythrocytes from young and aged rabbits.


RESULTS
S. aureus keratitis produced significantly higher SLE scores in young rabbits than in aged rabbits at 15, 20, and 25 hours postinfection (PI; P < or = 0.001); aged rabbits essentially recovered from S. aureus keratitis by 7 days PI. At 25 hours PI, numbers of CFUs and PMNs in corneas of young and aged rabbits were equivalent (P > or = 0.6); the bacterial burden in aged rabbits declined by 5 logs per cornea from day 1 to day 7 PI. Intrastromal injection of > or =10 HU alpha-toxin also produced significantly more disease in young than in aged rabbit corneas (P < or = 0.05), whereas 1 HU or heat-inactivated toxin yielded negligible pathologic changes in either group. Hemolysis assays of erythrocytes from young rabbits demonstrated greater susceptibility to alpha-toxin compared with those from aged rabbits.


CONCLUSIONS
Corneas and erythrocytes of young rabbits, relative to aged rabbits, are significantly more susceptible to S. aureus keratitis and to alpha-toxin.
O'Callaghan
Richard J
RJ
Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216, USA. rocallaghan@microbio.umsmed.edu
McCormick
Clare C
CC
Caballero
Armando R
AR
Marquart
Mary E
ME
Gatlin
Hattie P
HP
Fratkin
Jonathan D
JD
D000375:Aging / Q000502:physiology*; D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage; D015169:Colony Count, Microbial; D003319:Corneal Stroma / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D003320:Corneal Ulcer / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D015818:Eye Infections, Bacterial / Q000382:microbiology* / Q000473:pathology; D006460:Hemolysin Proteins / Q000008:administration & dosage; D007267:Injections; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D013203:Staphylococcal Infections / Q000382:microbiology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D014774:Virulence
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin; D009195:Peroxidase