Killing of Chlamydia trachomatis by novel antimicrobial lipids adapted from compounds in human breast milk.
The development of new methods for prevention of sexually transmitted Chlamydia trachomatis infection is a top public health priority. Topical self-administered vaginal microbicides represent one such approach in which the organism is eradicated at the time of initial exposure. To this end, we examined the activity of five synthetic lipids adapted from naturally occurring compounds found in human breast milk. C. trachomatis serovar D or F elementary bodies were added to serial dilutions of the lipids and incubated for various times. Aliquots were then cultured in monolayers of McCoy cells, and inclusions were counted. A 7.5 mM concentration of 2-O-octyl-sn-glycerol completely prevented growth of C. trachomatis after 120 min of contact with the organism. The remaining lipids, 1-O-octyl-, 1-O-heptyl-, 2-O-hexyl-, and 1-O-hexyl-sn-glycerol, showed less activity. On electron microscopic examination, the lipids were shown to have disrupted the chlamydial inner membrane, allowing leakage of the cytoplasmic contents from the cell. Lipid activity 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-octyl-sn-glycerol, may be effective as topical microbicides in preventing the transmission of C. trachomatis. Further efficacy and toxicity studies with these lipids and assessment of their activity against other sexually transmitted disease pathogens are in progress.
Lampe
M F
MF
University of Washington, Seattle 98195, USA. lampe@u.washington.edu
Ballweber
L M
LM
Isaacs
C E
CE
Patton
D L
DL
Stamm
W E
WE
D002692:Chlamydia trachomatis / Q000187:drug effects* / Q000648:ultrastructure; D004396:Coloring Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D006863:Hydrogen-Ion Concentration; D050356:Lipid Metabolism; D008055:Lipids / Q000138:chemical synthesis / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D008895:Milk, Human / Q000737:chemistry*; D010078:Oxazines; D014966:Xanthenes
D004396:Coloring Agents; D008055:Lipids; D010078:Oxazines; D014966:Xanthenes; C005843:resazurin