Isolation and characterization of Pseudomonas aeruginosa genes inducible by respiratory mucus derived from cystic fibrosis patients

被引:79
作者
Wang, JY
Lory, S
Ramphal, R
Jin, SG
机构
[1] UNIV ARKANSAS MED SCI HOSP,DEPT MICROBIOL & IMMUNOL,LITTLE ROCK,AR 72205
[2] UNIV WASHINGTON,DEPT MICROBIOL,SEATTLE,WA 98195
[3] UNIV FLORIDA,DEPT INFECT DIS,GAINESVILLE,FL 32610
关键词
D O I
10.1046/j.1365-2958.1996.01533.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pseudomonas aeruginosa, an opportunistic human pathogen, is a major causative agent of mortality and morbidity in immunocompromised individuals and those with cystic fibrosis (CF). in OF patients, the secretion of abnormally high amounts of mucus into the airways contributes to their susceptibility to infection by P. aeruginosa. To identify virulence genes of P. aeruginosa that are important in infection of CF patients, an in vivo selection system (IVET) was used to identify promoters that are specifically inducible by respiratory mucus derived from OF patients, Three genetic loci that are highly inducible by the mucus were identified, One of them is a well-characterized virulence gene (fptA), encoding the receptor for pyochelin, which is a P. aeruginosa iron siderophore. Induction of the fptA gene by mucus is suppressed by the addition of exogenous iron, demonstrating that the mucus is an iron chelator and generates an iron-deficient environment in OF lungs. Therefore, as a part of the host-defence mechanism, the mucus could also be responsible for induction of iron-regulated virulence factors of bacterial pathogens, The second locus, np20, encodes a peptide that shares sequence homology to a number of transcriptional regulators, An identical locus was previously identified to be inducible in vivo during infection of mice and was shown to be important in bacterial virulence in a neutropenic-mouse infection model, The third locus, designated migA (mucus Inducible gene), was sequenced and found to encode a 299-amino-acid peptide which is homologous to glycosyltransferases of other bacteria, and is involved in the biosynthesis of lipopolysaccharides or exopolysaccharides. Inducibilities of the np20 and migA genes are not affected by iron and the exact nature of the inducing signals in the mucus is not known, The possible implications of the migA inducibility by respiratory mucus is discussed in relation to the P. aeruginosa infection in CF.
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收藏
页码:1005 / 1012
页数:8
相关论文
共 31 条
[1]   EFFECTS OF SIDEROPHORES ON THE GROWTH OF PSEUDOMONAS-AERUGINOSA IN HUMAN-SERUM AND TRANSFERRIN [J].
ANKENBAUER, R ;
SRIYOSACHATI, S ;
COX, CD .
INFECTION AND IMMUNITY, 1985, 49 (01) :132-140
[2]   FPTA, THE FE(III)-PYOCHELIN RECEPTOR OF PSEUDOMONAS-AERUGINOSA - A PHENOLATE SIDEROPHORE RECEPTOR HOMOLOGOUS TO HYDROXAMATE SIDEROPHORE RECEPTORS [J].
ANKENBAUER, RG ;
QUAN, HN .
JOURNAL OF BACTERIOLOGY, 1994, 176 (02) :307-319
[4]  
BJORN MJ, 1978, INFECT IMMUN, V19, P785, DOI 10.1128/IAI.19.3.785-791.1978
[5]   MOLECULAR ANALYSIS OF THE AMS OPERON REQUIRED FOR EXOPOLYSACCHARIDE SYNTHESIS OF ERWINIA-AMYLOVORA [J].
BUGERT, P ;
GEIDER, K .
MOLECULAR MICROBIOLOGY, 1995, 15 (05) :917-933
[6]   ALTERED CARBOHYDRATE-COMPOSITION OF SALIVARY MUCINS FROM PATIENTS WITH CYSTIC-FIBROSIS AND THE ADHESION OF PSEUDOMONAS-AERUGINOSA [J].
CARNOY, C ;
RAMPHAL, R ;
SCHARFMAN, A ;
LOGUIDICE, JM ;
HOUDRET, N ;
KLEIN, A ;
GALABERT, C ;
LAMBLIN, G ;
ROUSSEL, P .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1993, 9 (03) :323-334
[7]   PSEUDOMONAS-AERUGINOSA OUTER-MEMBRANE ADHESINS FOR HUMAN RESPIRATORY MUCUS GLYCOPROTEINS [J].
CARNOY, C ;
SCHARFMAN, A ;
VANBRUSSEL, E ;
LAMBLIN, G ;
RAMPHAL, R ;
ROUSSEL, P .
INFECTION AND IMMUNITY, 1994, 62 (05) :1896-1900
[8]   EFFECT OF PYOCHELIN ON THE VIRULENCE OF PSEUDOMONAS-AERUGINOSA [J].
COX, CD .
INFECTION AND IMMUNITY, 1982, 36 (01) :17-23
[9]   MUTANTS OF ESCHERICHIA-COLI REQUIRING METHIONINE OR VITAMIN-B12 [J].
DAVIS, BD ;
MINGIOLI, ES .
JOURNAL OF BACTERIOLOGY, 1950, 60 (01) :17-28
[10]   WHOLE-GENOME RANDOM SEQUENCING AND ASSEMBLY OF HAEMOPHILUS-INFLUENZAE RD [J].
FLEISCHMANN, RD ;
ADAMS, MD ;
WHITE, O ;
CLAYTON, RA ;
KIRKNESS, EF ;
KERLAVAGE, AR ;
BULT, CJ ;
TOMB, JF ;
DOUGHERTY, BA ;
MERRICK, JM ;
MCKENNEY, K ;
SUTTON, G ;
FITZHUGH, W ;
FIELDS, C ;
GOCAYNE, JD ;
SCOTT, J ;
SHIRLEY, R ;
LIU, LI ;
GLODEK, A ;
KELLEY, JM ;
WEIDMAN, JF ;
PHILLIPS, CA ;
SPRIGGS, T ;
HEDBLOM, E ;
COTTON, MD ;
UTTERBACK, TR ;
HANNA, MC ;
NGUYEN, DT ;
SAUDEK, DM ;
BRANDON, RC ;
FINE, LD ;
FRITCHMAN, JL ;
FUHRMANN, JL ;
GEOGHAGEN, NSM ;
GNEHM, CL ;
MCDONALD, LA ;
SMALL, KV ;
FRASER, CM ;
SMITH, HO ;
VENTER, JC .
SCIENCE, 1995, 269 (5223) :496-512