Salmonella enterica serovar Typhi plasmid pR ST98 enhances intracellular bacterial growth and S. typhi-induced macrophage cell death by suppressing autophagy

OBJECTIVES: Plasmid pR ST98 is a hybrid resistance-virulence plasmid isolated from Salmonella enterica serovar Typhi (S. typhi). Previous studies demonstrated that pR ST98 could enhance the virulence of its host bacteria. However, the mechanism of pR ST98-increased bacterial virulence is still not f...

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Main Authors: Peiyan He, Shuyan Wu, Yuanyuan Chu, Yanru Yang, Yuanyuan Li, Rui Huang
Format: Article
Sprog:English
Udgivet: Elsevier
Serier:Brazilian Journal of Infectious Diseases
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Online adgang:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702012000300008&lng=en&tlng=en
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author Peiyan He
Shuyan Wu
Yuanyuan Chu
Yanru Yang
Yuanyuan Li
Rui Huang
author_facet Peiyan He
Shuyan Wu
Yuanyuan Chu
Yanru Yang
Yuanyuan Li
Rui Huang
author_sort Peiyan He
collection DOAJ
description OBJECTIVES: Plasmid pR ST98 is a hybrid resistance-virulence plasmid isolated from Salmonella enterica serovar Typhi (S. typhi). Previous studies demonstrated that pR ST98 could enhance the virulence of its host bacteria. However, the mechanism of pR ST98-increased bacterial virulence is still not fully elucidated. This study was designed to gain further insight into the roles of pR ST98 in host responses. METHODS: Human-derived macrophage-like cell line THP-1 was infected with wild-type (ST8), pR ST98-deletion (ST8-ΔpR ST98), and complemented (ST8-c-pR ST98) S. typhi strains. Macrophage autophagy was performed by extracting the membrane-unbound LC3-I protein from cells, followed by flow cytometric detection of the membrane-associated fraction of LC3-II. Intracellular bacterial growth was determined by colony-forming units (cfu) assay. Macrophage cell death was measured by flow cytometry after propidium iodide (PI) staining. Autophagy activator rapamycin (RAPA) was added to the medium 2 h before infection to investigate the effect of autophagy on intracellular bacterial growth and macrophage cell death after S. typhi infection. RESULTS: Plasmid pR ST98 suppressed autophagy in infected macrophages and enhanced intracellular bacterial growth and S. typhi-induced macrophage cell death. Pretreatment with RAPA effectively restricted intracellular bacterial growth of ST8 and ST8-c-pR ST98, and alleviated ST8 and ST8-c-pR ST98-induced macrophage cell death, but had no significant effect on ST8-ΔpR ST98. CONCLUSIONS: Plasmid pR ST98 enhances intracellular bacterial growth and S. typhi-induced macrophage cell death by suppressing autophagy.
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spelling doaj.art-ad768722f5974111a25530e03be901b32022-12-21T20:04:16ZengElsevierBrazilian Journal of Infectious Diseases1678-439116326226610.1590/S1413-86702012000300008S1413-86702012000300008Salmonella enterica serovar Typhi plasmid pR ST98 enhances intracellular bacterial growth and S. typhi-induced macrophage cell death by suppressing autophagyPeiyan He0Shuyan Wu1Yuanyuan Chu2Yanru Yang3Yuanyuan Li4Rui Huang5Soochow UniversitySoochow UniversitySoochow UniversitySoochow UniversitySoochow UniversitySoochow UniversityOBJECTIVES: Plasmid pR ST98 is a hybrid resistance-virulence plasmid isolated from Salmonella enterica serovar Typhi (S. typhi). Previous studies demonstrated that pR ST98 could enhance the virulence of its host bacteria. However, the mechanism of pR ST98-increased bacterial virulence is still not fully elucidated. This study was designed to gain further insight into the roles of pR ST98 in host responses. METHODS: Human-derived macrophage-like cell line THP-1 was infected with wild-type (ST8), pR ST98-deletion (ST8-ΔpR ST98), and complemented (ST8-c-pR ST98) S. typhi strains. Macrophage autophagy was performed by extracting the membrane-unbound LC3-I protein from cells, followed by flow cytometric detection of the membrane-associated fraction of LC3-II. Intracellular bacterial growth was determined by colony-forming units (cfu) assay. Macrophage cell death was measured by flow cytometry after propidium iodide (PI) staining. Autophagy activator rapamycin (RAPA) was added to the medium 2 h before infection to investigate the effect of autophagy on intracellular bacterial growth and macrophage cell death after S. typhi infection. RESULTS: Plasmid pR ST98 suppressed autophagy in infected macrophages and enhanced intracellular bacterial growth and S. typhi-induced macrophage cell death. Pretreatment with RAPA effectively restricted intracellular bacterial growth of ST8 and ST8-c-pR ST98, and alleviated ST8 and ST8-c-pR ST98-induced macrophage cell death, but had no significant effect on ST8-ΔpR ST98. CONCLUSIONS: Plasmid pR ST98 enhances intracellular bacterial growth and S. typhi-induced macrophage cell death by suppressing autophagy.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702012000300008&lng=en&tlng=enplasmid pR ST98macrophageautophagyintracellular bacterial growthcell death
spellingShingle Peiyan He
Shuyan Wu
Yuanyuan Chu
Yanru Yang
Yuanyuan Li
Rui Huang
Salmonella enterica serovar Typhi plasmid pR ST98 enhances intracellular bacterial growth and S. typhi-induced macrophage cell death by suppressing autophagy
Brazilian Journal of Infectious Diseases
plasmid pR ST98
macrophage
autophagy
intracellular bacterial growth
cell death
title Salmonella enterica serovar Typhi plasmid pR ST98 enhances intracellular bacterial growth and S. typhi-induced macrophage cell death by suppressing autophagy
title_full Salmonella enterica serovar Typhi plasmid pR ST98 enhances intracellular bacterial growth and S. typhi-induced macrophage cell death by suppressing autophagy
title_fullStr Salmonella enterica serovar Typhi plasmid pR ST98 enhances intracellular bacterial growth and S. typhi-induced macrophage cell death by suppressing autophagy
title_full_unstemmed Salmonella enterica serovar Typhi plasmid pR ST98 enhances intracellular bacterial growth and S. typhi-induced macrophage cell death by suppressing autophagy
title_short Salmonella enterica serovar Typhi plasmid pR ST98 enhances intracellular bacterial growth and S. typhi-induced macrophage cell death by suppressing autophagy
title_sort salmonella enterica serovar typhi plasmid pr st98 enhances intracellular bacterial growth and s typhi induced macrophage cell death by suppressing autophagy
topic plasmid pR ST98
macrophage
autophagy
intracellular bacterial growth
cell death
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702012000300008&lng=en&tlng=en
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