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A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa
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نویسنده
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cao q. ,wang y. ,chen f. ,xia y. ,lou j. ,zhang x. ,yang n. ,sun x. ,zhang q. ,zhuo c. ,huang x. ,deng x. ,yang c.-g. ,ye y. ,zhao j. ,wu m. ,lan l.
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منبع
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plos pathogens - 2014 - دوره : 10 - شماره : 8
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چکیده
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The rhl quorum-sensing (qs) system plays critical roles in the pathogenesis of p. aeruginosa. however,the regulatory effects that occur directly upstream of the rhl qs system are poorly understood. here,we show that deletion of gene encoding for the two-component sensor bfms leads to the activation of its cognate response regulator bfmr,which in turn directly binds to the promoter and decreases the expression of the rhlr gene that encodes the qs regulator rhlr,causing the inhibition of the rhl qs system. in the absence of bfms,the acka-pta pathway can modulate the regulatory activity of bfmr. in addition,bfms tunes the expression of 202 genes that comprise 3.6% of the p. aeruginosa genome. we further demonstrate that deletion of bfms causes substantially reduced virulence in lettuce leaf,reduced cytotoxicity,enhanced invasion,and reduced bacterial survival during acute mouse lung infection. intriguingly,specific missense mutations,which occur naturally in the bfms gene in p. aeruginosa cystic fibrosis (cf) isolates such as dk2 strains and rp73 strain,can produce bfms variants (bfmsl181p,bfmsl181p/e376q,and bfmsr393h) that no longer repress,but instead activate bfmr. as a result,bfms variants,but not the wild-type bfms,inhibit the rhl qs system. this study thus uncovers a previously unexplored signal transduction pathway,bfms/bfmr/rhlr,for the regulation of rhl qs in p. aeruginosa. we propose that bfmrs tcs may have an important role in the regulation and evolution of p. aeruginosa virulence during chronic infection in cf lungs. © 2014 cao et al.
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آدرس
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hainan university,haikou,hainan,china,shanghai institute of materia medica,chinese academy of sciences,shanghai, China, shanghai institute of materia medica,chinese academy of sciences,shanghai,china,institute of chemistry and biomedical sciences,state key laboratory of pharmaceutical biotechnology,school of life sciences,nanjing university,nanjing, China, shanghai institute of materia medica,chinese academy of sciences,shanghai, China, shanghai institute of materia medica,chinese academy of sciences,shanghai, China, shanghai institute of materia medica,chinese academy of sciences,shanghai, China, shanghai institute of materia medica,chinese academy of sciences,shanghai, China, shanghai institute of materia medica,chinese academy of sciences,shanghai, China, shanghai institute of materia medica,chinese academy of sciences,shanghai, China, state key laboratory of respiratory diseases,first affiliated hospital of guangzhou medical college,guangzhou, China, state key laboratory of respiratory diseases,first affiliated hospital of guangzhou medical college,guangzhou, China, hainan university,haikou,hainan, China, department of chemistry and institute for biophysical dynamics,the university of chicago,chicago,il, United States, shanghai institute of materia medica,chinese academy of sciences,shanghai, China, department of basic sciences,university of north dakota school of medicine and health sciences,grand forks,nd, United States, institute of chemistry and biomedical sciences,state key laboratory of pharmaceutical biotechnology,school of life sciences,nanjing university,nanjing, China, department of basic sciences,university of north dakota school of medicine and health sciences,grand forks,nd, United States, shanghai institute of materia medica,chinese academy of sciences,shanghai, China
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Authors
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