Chlamydia species-dependent differences in the growth requirement for lysosomes.
Genome reduction is a hallmark of obligate intracellular pathogens such as Chlamydia, where adaptation to intracellular growth has resulted in the elimination of genes encoding biosynthetic enzymes. Accordingly, chlamydiae rely heavily on the host cell for nutrients yet their specific source is uncl...
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| Format: | Article |
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Public Library of Science (PLoS)
2011-03-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0016783&type=printable |
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| author | Scot P Ouellette Frank C Dorsey Simon Moshiach John L Cleveland Rey A Carabeo |
| author_facet | Scot P Ouellette Frank C Dorsey Simon Moshiach John L Cleveland Rey A Carabeo |
| author_sort | Scot P Ouellette |
| collection | DOAJ |
| description | Genome reduction is a hallmark of obligate intracellular pathogens such as Chlamydia, where adaptation to intracellular growth has resulted in the elimination of genes encoding biosynthetic enzymes. Accordingly, chlamydiae rely heavily on the host cell for nutrients yet their specific source is unclear. Interestingly, chlamydiae grow within a pathogen-defined vacuole that is in close apposition to lysosomes. Metabolically-labeled uninfected host cell proteins were provided as an exogenous nutrient source to chlamydiae-infected cells, and uptake and subsequent labeling of chlamydiae suggested lysosomal degradation as a source of amino acids for the pathogen. Indeed, Bafilomycin A1 (BafA1), an inhibitor of the vacuolar H(+)/ATPase that blocks lysosomal acidification and functions, impairs the growth of C. trachomatis and C. pneumoniae, and these effects are especially profound in C. pneumoniae. BafA1 induced the marked accumulation of material within the lysosomal lumen, which was due to the inhibition of proteolytic activities, and this response inhibits chlamydiae rather than changes in lysosomal acidification per se, as cathepsin inhibitors also inhibit the growth of chlamydiae. Finally, the addition of cycloheximide, an inhibitor of eukaryotic protein synthesis, compromises the ability of lysosomal inhibitors to block chlamydial growth, suggesting chlamydiae directly access free amino acids in the host cytosol as a preferred source of these nutrients. Thus, chlamydiae co-opt the functions of lysosomes to acquire essential amino acids. |
| format | Article |
| id | doaj-art-41e40317d6144fc996f1e6a893407997 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2011-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-41e40317d6144fc996f1e6a8934079972025-08-20T03:45:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-03-0163e1678310.1371/journal.pone.0016783Chlamydia species-dependent differences in the growth requirement for lysosomes.Scot P OuelletteFrank C DorseySimon MoshiachJohn L ClevelandRey A CarabeoGenome reduction is a hallmark of obligate intracellular pathogens such as Chlamydia, where adaptation to intracellular growth has resulted in the elimination of genes encoding biosynthetic enzymes. Accordingly, chlamydiae rely heavily on the host cell for nutrients yet their specific source is unclear. Interestingly, chlamydiae grow within a pathogen-defined vacuole that is in close apposition to lysosomes. Metabolically-labeled uninfected host cell proteins were provided as an exogenous nutrient source to chlamydiae-infected cells, and uptake and subsequent labeling of chlamydiae suggested lysosomal degradation as a source of amino acids for the pathogen. Indeed, Bafilomycin A1 (BafA1), an inhibitor of the vacuolar H(+)/ATPase that blocks lysosomal acidification and functions, impairs the growth of C. trachomatis and C. pneumoniae, and these effects are especially profound in C. pneumoniae. BafA1 induced the marked accumulation of material within the lysosomal lumen, which was due to the inhibition of proteolytic activities, and this response inhibits chlamydiae rather than changes in lysosomal acidification per se, as cathepsin inhibitors also inhibit the growth of chlamydiae. Finally, the addition of cycloheximide, an inhibitor of eukaryotic protein synthesis, compromises the ability of lysosomal inhibitors to block chlamydial growth, suggesting chlamydiae directly access free amino acids in the host cytosol as a preferred source of these nutrients. Thus, chlamydiae co-opt the functions of lysosomes to acquire essential amino acids.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0016783&type=printable |
| spellingShingle | Scot P Ouellette Frank C Dorsey Simon Moshiach John L Cleveland Rey A Carabeo Chlamydia species-dependent differences in the growth requirement for lysosomes. PLoS ONE |
| title | Chlamydia species-dependent differences in the growth requirement for lysosomes. |
| title_full | Chlamydia species-dependent differences in the growth requirement for lysosomes. |
| title_fullStr | Chlamydia species-dependent differences in the growth requirement for lysosomes. |
| title_full_unstemmed | Chlamydia species-dependent differences in the growth requirement for lysosomes. |
| title_short | Chlamydia species-dependent differences in the growth requirement for lysosomes. |
| title_sort | chlamydia species dependent differences in the growth requirement for lysosomes |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0016783&type=printable |
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