The perilipin‐like PPE15 protein in Mycobacterium tuberculosis is required for triacylglycerol accumulation under dormancy‐inducing conditions
Summary Mycobacterium tuberculosis (Mtb) causes latent tuberculosis infection in one‐third of the world population and remains quiescent in the human body for decades. The dormant pathogen accumulates lipid droplets containing triacylglycerol (TAG). In mammals, perilipin regulates lipid droplet home...
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Veröffentlicht in: | Molecular microbiology 2016-09, Vol.101 (5), p.784-794 |
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creator | Daniel, Jaiyanth Kapoor, Nidhi Sirakova, Tatiana Sinha, Rajesh Kolattukudy, Pappachan |
description | Summary
Mycobacterium tuberculosis (Mtb) causes latent tuberculosis infection in one‐third of the world population and remains quiescent in the human body for decades. The dormant pathogen accumulates lipid droplets containing triacylglycerol (TAG). In mammals, perilipin regulates lipid droplet homeostasis but no such protein has been identified in Mtb. We identified an Mtb protein (PPE15) that showed weak amino acid sequence identities with mammalian perilipin‐1 and was upregulated in Mtb dormancy. We generated a ppe15 gene‐disrupted mutant of Mtb and examined its ability to metabolically incorporate radiolabeled oleic acid into TAG, accumulate lipid droplets containing TAG and develop phenotypic tolerance to rifampicin in two in vitro models of dormancy including a three‐dimensional human granuloma model. The mutant showed a significant decrease in the biosynthesis and accumulation of lipid droplets containing TAG and in its tolerance of rifampicin. Complementation of the mutant with a wild‐type copy of the ppe15 gene restored the lost phenotypes. We designate PPE15 as mycobacterial perilipin‐1 (MPER1). Our findings suggest that the MPER1 protein plays a critical role in the homeostasis of TAG ‐containing lipid droplets in Mtb and influences the entry of the pathogen into a dormant state.
Triacylglycerol accumulation inside Mycobacterium tuberculosis is associated with its entry into a drug‐tolerant, dormant state. The mycobacterial ppe15 gene is shown in this study to be essential for the accumulation of lipid droplets under dormancy‐inducing conditions. Deletion of the ppe15 gene diminished the ability of the pathogen to accumulate triacylglycerol in lipid droplets and decreased its ability to develop phenotypic tolerance to rifampicin in the multiple‐stress and in vitro granuloma models of dormancy. |
doi_str_mv | 10.1111/mmi.13422 |
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Mycobacterium tuberculosis (Mtb) causes latent tuberculosis infection in one‐third of the world population and remains quiescent in the human body for decades. The dormant pathogen accumulates lipid droplets containing triacylglycerol (TAG). In mammals, perilipin regulates lipid droplet homeostasis but no such protein has been identified in Mtb. We identified an Mtb protein (PPE15) that showed weak amino acid sequence identities with mammalian perilipin‐1 and was upregulated in Mtb dormancy. We generated a ppe15 gene‐disrupted mutant of Mtb and examined its ability to metabolically incorporate radiolabeled oleic acid into TAG, accumulate lipid droplets containing TAG and develop phenotypic tolerance to rifampicin in two in vitro models of dormancy including a three‐dimensional human granuloma model. The mutant showed a significant decrease in the biosynthesis and accumulation of lipid droplets containing TAG and in its tolerance of rifampicin. Complementation of the mutant with a wild‐type copy of the ppe15 gene restored the lost phenotypes. We designate PPE15 as mycobacterial perilipin‐1 (MPER1). Our findings suggest that the MPER1 protein plays a critical role in the homeostasis of TAG ‐containing lipid droplets in Mtb and influences the entry of the pathogen into a dormant state.
Triacylglycerol accumulation inside Mycobacterium tuberculosis is associated with its entry into a drug‐tolerant, dormant state. The mycobacterial ppe15 gene is shown in this study to be essential for the accumulation of lipid droplets under dormancy‐inducing conditions. Deletion of the ppe15 gene diminished the ability of the pathogen to accumulate triacylglycerol in lipid droplets and decreased its ability to develop phenotypic tolerance to rifampicin in the multiple‐stress and in vitro granuloma models of dormancy.</description><identifier>ISSN: 0950-382X</identifier><identifier>EISSN: 1365-2958</identifier><identifier>DOI: 10.1111/mmi.13422</identifier><identifier>PMID: 27325376</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Amino Acid Sequence ; Antigens, Bacterial - genetics ; Antigens, Bacterial - metabolism ; Conserved Sequence ; Homeostasis ; Host-Pathogen Interactions ; Humans ; Latent Tuberculosis - microbiology ; Lipid Metabolism ; Lipids ; Mammals ; Mutation ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - genetics ; Mycobacterium tuberculosis - metabolism ; Pathogens ; Perilipin-1 - genetics ; Perilipin-1 - metabolism ; Proteins ; Sequence Analysis, Protein - methods ; Triglycerides - metabolism ; Tuberculosis</subject><ispartof>Molecular microbiology, 2016-09, Vol.101 (5), p.784-794</ispartof><rights>2016 John Wiley & Sons Ltd</rights><rights>2016 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4762-7bf2880e979f0354ba8529e6943d01dca9dd8110486851ee63c9e11f09bc8baa3</citedby><cites>FETCH-LOGICAL-c4762-7bf2880e979f0354ba8529e6943d01dca9dd8110486851ee63c9e11f09bc8baa3</cites><orcidid>0000-0002-3605-687X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fmmi.13422$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fmmi.13422$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27325376$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Daniel, Jaiyanth</creatorcontrib><creatorcontrib>Kapoor, Nidhi</creatorcontrib><creatorcontrib>Sirakova, Tatiana</creatorcontrib><creatorcontrib>Sinha, Rajesh</creatorcontrib><creatorcontrib>Kolattukudy, Pappachan</creatorcontrib><title>The perilipin‐like PPE15 protein in Mycobacterium tuberculosis is required for triacylglycerol accumulation under dormancy‐inducing conditions</title><title>Molecular microbiology</title><addtitle>Mol Microbiol</addtitle><description>Summary
Mycobacterium tuberculosis (Mtb) causes latent tuberculosis infection in one‐third of the world population and remains quiescent in the human body for decades. The dormant pathogen accumulates lipid droplets containing triacylglycerol (TAG). In mammals, perilipin regulates lipid droplet homeostasis but no such protein has been identified in Mtb. We identified an Mtb protein (PPE15) that showed weak amino acid sequence identities with mammalian perilipin‐1 and was upregulated in Mtb dormancy. We generated a ppe15 gene‐disrupted mutant of Mtb and examined its ability to metabolically incorporate radiolabeled oleic acid into TAG, accumulate lipid droplets containing TAG and develop phenotypic tolerance to rifampicin in two in vitro models of dormancy including a three‐dimensional human granuloma model. The mutant showed a significant decrease in the biosynthesis and accumulation of lipid droplets containing TAG and in its tolerance of rifampicin. Complementation of the mutant with a wild‐type copy of the ppe15 gene restored the lost phenotypes. We designate PPE15 as mycobacterial perilipin‐1 (MPER1). Our findings suggest that the MPER1 protein plays a critical role in the homeostasis of TAG ‐containing lipid droplets in Mtb and influences the entry of the pathogen into a dormant state.
Triacylglycerol accumulation inside Mycobacterium tuberculosis is associated with its entry into a drug‐tolerant, dormant state. The mycobacterial ppe15 gene is shown in this study to be essential for the accumulation of lipid droplets under dormancy‐inducing conditions. Deletion of the ppe15 gene diminished the ability of the pathogen to accumulate triacylglycerol in lipid droplets and decreased its ability to develop phenotypic tolerance to rifampicin in the multiple‐stress and in vitro granuloma models of dormancy.</description><subject>Amino Acid Sequence</subject><subject>Antigens, Bacterial - genetics</subject><subject>Antigens, Bacterial - metabolism</subject><subject>Conserved Sequence</subject><subject>Homeostasis</subject><subject>Host-Pathogen Interactions</subject><subject>Humans</subject><subject>Latent Tuberculosis - microbiology</subject><subject>Lipid Metabolism</subject><subject>Lipids</subject><subject>Mammals</subject><subject>Mutation</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - genetics</subject><subject>Mycobacterium tuberculosis - metabolism</subject><subject>Pathogens</subject><subject>Perilipin-1 - genetics</subject><subject>Perilipin-1 - metabolism</subject><subject>Proteins</subject><subject>Sequence Analysis, Protein - methods</subject><subject>Triglycerides - metabolism</subject><subject>Tuberculosis</subject><issn>0950-382X</issn><issn>1365-2958</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks9qFTEUh4Mo9lpd-AIScKOLafNnJjPZCFKqFnqxiwruQiZz5jY1k9wmE2V2PoL4iD6JaW8tKgiGA1nk48s5yQ-hp5Qc0LIOp8keUF4zdg-tKBdNxWTT3UcrIhtS8Y593EOPUrokhHIi-EO0x1rOGt6KFfp-fgF4C9E6u7X-x9dvzn4CfHZ2TBu8jWEG63Gp9WJCr81cwDzhOfcQTXYh2YRLRbjKNsKAxxDxHK02i9u4xUAMDmtj8pSdnm3wOPsBIh5CnLQ3S7nO-iEb6zfYBD_YayY9Rg9G7RI8ud330Yc3x-dH76rT929Pjl6fVqZuBavafmRdR0C2ciS8qXvdNUyCkDUfCB2MlsPQUUrqTnQNBRDcSKB0JLI3Xa8130evdt5t7icYDPg5aqe20U46Lipoq_488fZCbcJn1RAqKRNF8OJWEMNVhjSrySYDzmkPISdFO9ZKwuu2_Q-U1kKwVjQFff4Xehly9OUlbqjyp2XCQr3cUSaGlCKMd31Toq5DoUoo1E0oCvvs90HvyF8pKMDhDvhiHSz_Nqn1-mSn_AkvM8af</recordid><startdate>201609</startdate><enddate>201609</enddate><creator>Daniel, Jaiyanth</creator><creator>Kapoor, Nidhi</creator><creator>Sirakova, Tatiana</creator><creator>Sinha, Rajesh</creator><creator>Kolattukudy, Pappachan</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3605-687X</orcidid></search><sort><creationdate>201609</creationdate><title>The perilipin‐like PPE15 protein in Mycobacterium tuberculosis is required for triacylglycerol accumulation under dormancy‐inducing conditions</title><author>Daniel, Jaiyanth ; Kapoor, Nidhi ; Sirakova, Tatiana ; Sinha, Rajesh ; Kolattukudy, Pappachan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4762-7bf2880e979f0354ba8529e6943d01dca9dd8110486851ee63c9e11f09bc8baa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Amino Acid Sequence</topic><topic>Antigens, Bacterial - genetics</topic><topic>Antigens, Bacterial - metabolism</topic><topic>Conserved Sequence</topic><topic>Homeostasis</topic><topic>Host-Pathogen Interactions</topic><topic>Humans</topic><topic>Latent Tuberculosis - microbiology</topic><topic>Lipid Metabolism</topic><topic>Lipids</topic><topic>Mammals</topic><topic>Mutation</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - genetics</topic><topic>Mycobacterium tuberculosis - metabolism</topic><topic>Pathogens</topic><topic>Perilipin-1 - genetics</topic><topic>Perilipin-1 - metabolism</topic><topic>Proteins</topic><topic>Sequence Analysis, Protein - methods</topic><topic>Triglycerides - metabolism</topic><topic>Tuberculosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Daniel, Jaiyanth</creatorcontrib><creatorcontrib>Kapoor, Nidhi</creatorcontrib><creatorcontrib>Sirakova, Tatiana</creatorcontrib><creatorcontrib>Sinha, Rajesh</creatorcontrib><creatorcontrib>Kolattukudy, Pappachan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Daniel, Jaiyanth</au><au>Kapoor, Nidhi</au><au>Sirakova, Tatiana</au><au>Sinha, Rajesh</au><au>Kolattukudy, Pappachan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The perilipin‐like PPE15 protein in Mycobacterium tuberculosis is required for triacylglycerol accumulation under dormancy‐inducing conditions</atitle><jtitle>Molecular microbiology</jtitle><addtitle>Mol Microbiol</addtitle><date>2016-09</date><risdate>2016</risdate><volume>101</volume><issue>5</issue><spage>784</spage><epage>794</epage><pages>784-794</pages><issn>0950-382X</issn><eissn>1365-2958</eissn><abstract>Summary
Mycobacterium tuberculosis (Mtb) causes latent tuberculosis infection in one‐third of the world population and remains quiescent in the human body for decades. The dormant pathogen accumulates lipid droplets containing triacylglycerol (TAG). In mammals, perilipin regulates lipid droplet homeostasis but no such protein has been identified in Mtb. We identified an Mtb protein (PPE15) that showed weak amino acid sequence identities with mammalian perilipin‐1 and was upregulated in Mtb dormancy. We generated a ppe15 gene‐disrupted mutant of Mtb and examined its ability to metabolically incorporate radiolabeled oleic acid into TAG, accumulate lipid droplets containing TAG and develop phenotypic tolerance to rifampicin in two in vitro models of dormancy including a three‐dimensional human granuloma model. The mutant showed a significant decrease in the biosynthesis and accumulation of lipid droplets containing TAG and in its tolerance of rifampicin. Complementation of the mutant with a wild‐type copy of the ppe15 gene restored the lost phenotypes. We designate PPE15 as mycobacterial perilipin‐1 (MPER1). Our findings suggest that the MPER1 protein plays a critical role in the homeostasis of TAG ‐containing lipid droplets in Mtb and influences the entry of the pathogen into a dormant state.
Triacylglycerol accumulation inside Mycobacterium tuberculosis is associated with its entry into a drug‐tolerant, dormant state. The mycobacterial ppe15 gene is shown in this study to be essential for the accumulation of lipid droplets under dormancy‐inducing conditions. Deletion of the ppe15 gene diminished the ability of the pathogen to accumulate triacylglycerol in lipid droplets and decreased its ability to develop phenotypic tolerance to rifampicin in the multiple‐stress and in vitro granuloma models of dormancy.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>27325376</pmid><doi>10.1111/mmi.13422</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-3605-687X</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Sequence Antigens, Bacterial - genetics Antigens, Bacterial - metabolism Conserved Sequence Homeostasis Host-Pathogen Interactions Humans Latent Tuberculosis - microbiology Lipid Metabolism Lipids Mammals Mutation Mycobacterium tuberculosis Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - metabolism Pathogens Perilipin-1 - genetics Perilipin-1 - metabolism Proteins Sequence Analysis, Protein - methods Triglycerides - metabolism Tuberculosis |
title | The perilipin‐like PPE15 protein in Mycobacterium tuberculosis is required for triacylglycerol accumulation under dormancy‐inducing conditions |
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