Structure–Function Aspects of PstS in Multi-Drug–Resistant Pseudomonas aeruginosa

The increasing prevalence of multi-drug–resistant (MDR) strains of Pseudomonas aeruginosa among critically ill humans is of significant concern. In the current study, we show that MDR clinical isolates of P. aeruginosa representing three distinct genotypes that display high virulence against intesti...

Deskribapen osoa

Gorde:
Xehetasun bibliografikoak
Egile Nagusiak: Zaborina, Olga, Holbrook, Christopher, Chen, Yimei, Long, Jason, Zaborin, Alexander, Morozova, Irina, Fernandez, Hoylan, Wang, Yingmin, Turner, Jerrold R, Alverdy, John C
Formatua: Artikulua
Hizkuntza:English
Argitaratua: Public Library of Science 2008
Gaiak:
Research Article
Sarrera elektronikoa:https://ncbi.nlm.nih.gov/pmc/articles/PMC2242829/
https://ncbi.nlm.nih.gov/pubmed/18282104
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1371/journal.ppat.0040043
Etiketak: Etiketa erantsi
Etiketarik gabe, Izan zaitez lehena erregistro honi etiketa jartzen!
id pubmed-2242829
record_format dspace
spelling pubmed-22428292008-02-15 Structure–Function Aspects of PstS in Multi-Drug–Resistant Pseudomonas aeruginosa Zaborina, Olga Holbrook, Christopher Chen, Yimei Long, Jason Zaborin, Alexander Morozova, Irina Fernandez, Hoylan Wang, Yingmin Turner, Jerrold R Alverdy, John C PLoS Pathog Research Article The increasing prevalence of multi-drug–resistant (MDR) strains of Pseudomonas aeruginosa among critically ill humans is of significant concern. In the current study, we show that MDR clinical isolates of P. aeruginosa representing three distinct genotypes that display high virulence against intestinal epithelial cells, form novel appendage-like structures on their cell surfaces. These appendages contain PstS, an extracellular phosphate binding protein. Using anti-PstS antibodies, we determined that the PstS-rich appendages in MDR strains are involved in adherence to and disruption of the integrity of cultured intestinal epithelial cell monolayers. The outer surface–expressed PstS protein was also identified to be present in P. aeruginosa MPAO1, although to a lesser degree, and its role in conferring an adhesive and barrier disruptive phenotype against intestinal epithelial cells was confirmed using an isogenic ΔPstS mutant. Formation of the PstS rich appendages was induced during phosphate limitation and completely suppressed in phosphate-rich media. Injection of MDR strains directly into the intestinal tract of surgically injured mice, a known model of phosphate limitation, caused high mortality rates (60%–100%). Repletion of intestinal phosphate in this model completely prevented mortality. Finally, significantly less outer surface PstS was observed in the MPAO1 mutant ΔHxcR thus establishing a role for the alternative type II secretion system Hxc in outer surface PstS expression. Gene expression analysis performed by RT-PCR confirmed this finding and further demonstrated abundant expression of pstS analogous to pa5369, pstS analogous to pa0688/pa14–55410, and hxcX in MDR strains. Taken together, these studies provide evidence that outer surface PstS expression confers a highly virulent phenotype of MDR isolates against the intestinal epithelium that alters their adhesive and barrier disrupting properties against the intestinal epithelium. Public Library of Science 2008-02 2008-02-15 /pmc/articles/PMC2242829/ /pubmed/18282104 http://dx.doi.org/10.1371/journal.ppat.0040043 Text en © 2008 Zaborina et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
institution US National Library of Medicine
collection PubMed Central
language English
format Article
topic Research Article
spellingShingle Research Article
Zaborina, Olga
Holbrook, Christopher
Chen, Yimei
Long, Jason
Zaborin, Alexander
Morozova, Irina
Fernandez, Hoylan
Wang, Yingmin
Turner, Jerrold R
Alverdy, John C
Structure–Function Aspects of PstS in Multi-Drug–Resistant Pseudomonas aeruginosa
description The increasing prevalence of multi-drug–resistant (MDR) strains of Pseudomonas aeruginosa among critically ill humans is of significant concern. In the current study, we show that MDR clinical isolates of P. aeruginosa representing three distinct genotypes that display high virulence against intestinal epithelial cells, form novel appendage-like structures on their cell surfaces. These appendages contain PstS, an extracellular phosphate binding protein. Using anti-PstS antibodies, we determined that the PstS-rich appendages in MDR strains are involved in adherence to and disruption of the integrity of cultured intestinal epithelial cell monolayers. The outer surface–expressed PstS protein was also identified to be present in P. aeruginosa MPAO1, although to a lesser degree, and its role in conferring an adhesive and barrier disruptive phenotype against intestinal epithelial cells was confirmed using an isogenic ΔPstS mutant. Formation of the PstS rich appendages was induced during phosphate limitation and completely suppressed in phosphate-rich media. Injection of MDR strains directly into the intestinal tract of surgically injured mice, a known model of phosphate limitation, caused high mortality rates (60%–100%). Repletion of intestinal phosphate in this model completely prevented mortality. Finally, significantly less outer surface PstS was observed in the MPAO1 mutant ΔHxcR thus establishing a role for the alternative type II secretion system Hxc in outer surface PstS expression. Gene expression analysis performed by RT-PCR confirmed this finding and further demonstrated abundant expression of pstS analogous to pa5369, pstS analogous to pa0688/pa14–55410, and hxcX in MDR strains. Taken together, these studies provide evidence that outer surface PstS expression confers a highly virulent phenotype of MDR isolates against the intestinal epithelium that alters their adhesive and barrier disrupting properties against the intestinal epithelium.
author Zaborina, Olga
Holbrook, Christopher
Chen, Yimei
Long, Jason
Zaborin, Alexander
Morozova, Irina
Fernandez, Hoylan
Wang, Yingmin
Turner, Jerrold R
Alverdy, John C
author_facet Zaborina, Olga
Holbrook, Christopher
Chen, Yimei
Long, Jason
Zaborin, Alexander
Morozova, Irina
Fernandez, Hoylan
Wang, Yingmin
Turner, Jerrold R
Alverdy, John C
author_sort Zaborina, Olga
title Structure–Function Aspects of PstS in Multi-Drug–Resistant Pseudomonas aeruginosa
title_short Structure–Function Aspects of PstS in Multi-Drug–Resistant Pseudomonas aeruginosa
title_full Structure–Function Aspects of PstS in Multi-Drug–Resistant Pseudomonas aeruginosa
title_fullStr Structure–Function Aspects of PstS in Multi-Drug–Resistant Pseudomonas aeruginosa
title_full_unstemmed Structure–Function Aspects of PstS in Multi-Drug–Resistant Pseudomonas aeruginosa
title_sort structure–function aspects of psts in multi-drug–resistant pseudomonas aeruginosa
publisher Public Library of Science
publisher_facet Public Library of Science
publishDate 2008
url https://ncbi.nlm.nih.gov/pmc/articles/PMC2242829/
https://ncbi.nlm.nih.gov/pubmed/18282104
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1371/journal.ppat.0040043
_version_ 1760528120961564672

Antzeko izenburuak