Mf. Lampe et al., KILLING OF CHLAMYDIA-TRACHOMATIS BY NOVEL ANTIMICROBIAL LIPIDS ADAPTED FROM COMPOUNDS IN HUMAN BREAST-MILK, Antimicrobial agents and chemotherapy, 42(5), 1998, pp. 1239-1244
The development of new methods for prevention of sexually transmitted
Chlamydia trachomatis infection is a top public health priority. Topic
al self-administered vaginal microbicides represent one such approach
in which the organism is eradicated at the time of initial exposure. T
o this end, we examined the activity of five synthetic lipids adapted
from naturally occurring compounds found in human breast milk. C. trac
homatis serovar D or F elementary bodies were added to serial dilution
s of the lipids and incubated for various times. Aliquots were then cu
ltured in monolayers of McCoy cells, and inclusions were counted. A 7.
5 mM concentration of 2-O-octyl-sn-glycerol completely prevented growt
h of C. trachomatis after 120 min of contact with the organism. The re
maining lipids, 1-O-octyl-, 1-O-heptyl-, 2-O-hexyl-, and 1-O-hexyl-sn-
glycerol, showed less activity, On electron microscopic examination, t
he lipids were shown to have disrupted the chlamydial inner membrane,
allowing leakage of the cytoplasmic contents from the cell. Lipid acti
vity was unaffected by the presence of 10% human blood or alterations
in pH from 4.0 to 8.0, conditions reflecting those sometimes found in
the vagina. Our results suggest that these lipids, especially 2-O-octy
l-sn-glycerol, may be effective as topical microbicides in preventing
the transmission of C. trachomatis. Further efficacy and toxicity stud
ies with these lipids and assessment of their activity against other s
exually transmitted disease pathogens are in progress.