High Levels of Cyclic Di-GMP in Klebsiella pneumoniae Attenuate Virulence in the Lung.

Citation data:

Infection and immunity, ISSN: 1098-5522, Vol: 86, Issue: 2, Page: 734-742

Publication Year:
2017
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Repository URL:
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PMID:
29158434; 28232390
DOI:
10.1128/iai.00647-17; 10.1136/bmjqs-2016-006123; 10.5038/9780977674435.ch19; 10.5038/9780977674435.ch29; 10.5038/9780977674435.ch21; 10.5038/9780977674435.ch20; 10.5038/9780977674435.ch27; 10.5038/9780977674435.ch17; 10.5038/9780977674435.ch14; 10.5038/9780977674435.ch12; 10.5038/9780977674435.ch13; 10.5038/9780977674435.ch30; 10.5038/9780977674435.ch11; 10.5038/9780977674435.ch4; 10.5038/9780977674435.ch26; 10.5038/9780977674435.ch22; 10.5038/9780977674435.ch5; 10.5038/9780977674435.ch6; 10.5038/9780977674435.ch3; 10.5038/9780977674435.ch1; 10.5038/9780977674435.ch9; 10.5038/9780977674435.ch28; 10.5038/9780977674435.ch24; 10.5038/9780977674435; 10.5038/9780977674435.ch23; 10.5038/9780977674435.ch2; 10.5038/9780977674435.ch16; 10.5038/9780977674435.ch15; 10.5038/9780977674435.ch25; 10.5038/9780977674435.ch18; 10. i 142/s2010495214500080; 10. 1136/bmjqs- 2016- 006123; 10.html#/es/; 10.pdf#xml=http:/www.fultonhistory.com/dtsearch/dtisapi6.dll?cmd=getpdfhits; 10.html/full; 10.pdf#xml%3dhttp%3a/fultonhistory.com/dtsearch/dtisapi6.dll%3fcmd%3dgetpdfhits%26u%3d17588c39%26docid%3d6839331%26index%3dz%3a%5cindex%20o%2dg%2dt%26hitcount%3d3%26hits%3de06+e07+e08+%26searchform%3d%2ffulton%5fform%2ehtml%26.pdf; 10.html#path/pw/by-topic/industry-news/people/article/43032-people-week-of-5-3-10.html; 10.html#document/p2/a208676; 10.htm/#; 10.html#/apple_ref/doc/uid/tp40017145-sw1; 10.pdf#xml%3dhttp%3a/fultonhistory.com/dtsearch/dtisapi6.dll%3fcmd%3dgetpdfhits%26u%3d3cdb5c2d%26docid%3d12204882%26index%3dz%3a%5cindex%20i%2de%2dv%26hitcount%3d2%26hits%3d444+445+%26searchform%3d%2ffulton%5fform%2ehtml%26.pdf; 10.html#http:/media.mercedsunstar.com/smedia/2010/10/04/08/04_monsterfest_43.standalone.prod_affiliate.111.jpg2; 10.html#/apple_ref/doc/uid/tp40014484-sw1; 10.pdf#xml%3dhttp%3a/fultonhistory.com/dtsearch/dtisapi6.dll%3fcmd%3dgetpdfhits%26u%3d361fe5a4%26docid%3d932410%26index%3dz%3a%5cindex%20o%2dg%2dt%26hitcount%3d4%26hits%3d37+38+12c+12d+%26searchform%3d%2ffulton%5fnew%5fform%2ehtml%26.pdf; 10.htm#!page/101393/mode/1up--; 10.pdf#__bgbl__/*[%40attr_id%3d%27bgbl115s0010.pdf%27]__1438730698018; 10.htm#04-01/2; 10.pdf#xml=http:/fultonhistory.com/dtsearch/dtisapi6.dll?cmd=getpdfhits; 10.html#!/2011/01/ladies-trek-to-nagalapuram-dec-2010.html
ISBN:
9780977674435
Author(s):
Westbrook, Johanna I.; Li, Ling; Hooper, Tamara D.; Raban, Magda Z.; Middleton, Sandy; Lehnbom, Elin C.
Publisher(s):
University of South Florida Libraries; BMJ; American Society for Microbiology; BMJ Publishing Group ltd.
Tags:
Immunology and Microbiology; Medicine; machine learning; meta-analysis; metagenomics; statistical analysis; Nursing; Genetics and Genomics; Public Health; Statistics and Probability
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article description
The bacterial second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) has been shown to influence the expression of virulence factors in certain pathogenic bacteria, but little is known about its activity in the increasingly antibiotic-resistant pathogen Here, the expression in of a heterologous diguanylate cyclase increased the bacterial c-di-GMP concentration and attenuated pathogenesis in murine pneumonia. This attenuation remained evident in mice lacking the c-di-GMP sensor STING, indicating that the high c-di-GMP concentration exerted its influence not on host responses but on bacterial physiology. While serum resistance and capsule expression were unaffected by the increased c-di-GMP concentration, both type 3 and type 1 pili were strongly upregulated. Importantly, attenuation of virulence by high c-di-GMP levels was abrogated when type 1 pilus expression was silenced. We conclude that increased type 1 piliation may hamper virulence in the respiratory tract and that c-di-GMP signaling represents a potential therapeutic target for antibiotic-resistant in this niche.