Lipid rafts, caveolae, caveolin-1, and entry by Chlamydiae into host cells.
Obligate intracellular bacterial pathogens of the genus Chlamydia are reported to enter host cells by both clathrin-dependent and clathrin-independent processes. C. trachomatis serovar K recently was shown to enter cells via caveolae-like lipid raft domains. We asked here how widespread raft-mediated entry might be among the Chlamydia. We show that C. pneumoniae, an important cause of respiratory infections in humans that additionally is associated with cardiovascular disease, and C. psittaci, an important pathogen in domestic mammals and birds that also infects humans, each enter host cells via cholesterol-rich lipid raft microdomains. Further, we show that C. trachomatis serovars E and F also use these domains to enter host cells. The involvement of these membrane domains in the entry of these organisms was indicated by the sensitivity of their entry to the raft-disrupting agents Nystatin and filipin, and by their intracellular association with caveolin-1, a 22-kDa protein associated with the formation of caveolae in rafts. In contrast, caveolin-marked lipid raft domains do not mediate entry of C. trachomatis serovars A, 36B, and C, nor of LGV serovar L2 and MoPn. Finally, we show that entry of each of these chlamydial strains is independent of cellular expression of caveolin-1. Thus, entry via the Nystatin and filipin-sensitive pathway is dependent on lipid rafts containing cholesterol, rather than invaginated caveolae per se.
Stuart
Elizabeth S
ES
Department of Microbiology, University of Massachusetts, 203 Morrill Science Center IVN, Amherst, MA 01003-5720, USA. esstuart@microbio.umass.edu
Webley
Wilmore C
WC
Norkin
Leonard C
LC
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D021941:Caveolae / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism*; D002689:Chlamydia / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity*; D002690:Chlamydia Infections / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005057:Eukaryotic Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D005372:Filipin / Q000494:pharmacology; D006367:HeLa Cells; D006790:Host-Parasite Interactions / Q000187:drug effects / Q000502:physiology; D006801:Humans; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D009761:Nystatin / Q000494:pharmacology; D013045:Species Specificity
D000900:Anti-Bacterial Agents; C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D009761:Nystatin; D005372:Filipin; D002784:Cholesterol