Pulmonary infections in patients with cystic fibrosis

Rajan, Sujatha; Saiman, Lisa

doi:10.1053/srin.2002.31690

Cited by 210 publications

(169 citation statements)

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“…This data would suggest then that the number of H. influenzae isolates in CF groups is increasing over this period. This increase is worrisome since recently it has been showed that infection of CF patients with H. influenzae in infancy is associated with a significant lower FEV0.5 (-18.2%) [4]. We are unaware of any previous reports describing this trend in CF patients, with H. parainfluenzae.…”

Section: Discussionmentioning

confidence: 43%

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Haemophilus influenzae and Haemophilus parainfluenza in Cystic Fibrosis: 15 Years Experience

Ebbing¹,

Robertson

Robinson

2015

J Medical Microbiol Diagnosis

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Section: Discussionmentioning

confidence: 43%

“…The latter organism is regularly involved in chronic lung infections and acute exacerbations in CF patients and has recently been shown to be associated with lower lung function in infants with CF [3,4]. Although generally not regarded as a pathogen, H. parainfluenzae does occasionally cause infections in humans, including pneumonia [5].…”

Section: Introductionmentioning

confidence: 99%

Haemophilus influenzae and Haemophilus parainfluenza in Cystic Fibrosis: 15 Years Experience

Ebbing¹,

Robertson

Robinson

2015

J Medical Microbiol Diagnosis

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“…These in turn lead to impaired bacterial clearance from respiratory epithelial cells (Saiman and Siegel 2004). Pulmonary infections remain to be the greatest cause of morbidity and mortality leading to premature death in CF (Rajan and Saiman 2002).…”

Section: B Respiratory Syncytial Virus (Rsv) Parainfluenza Virus (Pmentioning

confidence: 99%

Viral Respiratory Tract Infections in Cystic Fibrosis

Wat¹

2012

Cystic Fibrosis - Renewed Hopes Through Research

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“…In addition to engendering a range of nosocomial infections, including keratitis (Green et al, 2008), burn wounds (de Macedo & Santos, 2005), endocarditis (Baddour et al, 2005) and implanted medical devices (Hidron et al, 2008), it also colonizes the lungs of 80 % of persons with the heritable disease cystic fibrosis (CF) (Rajan & Saiman, 2002;Rosenfeld et al, 2003). Colonization by P. aeruginosa contributes to the decline of lung function in this patient population (Rajan & Saiman, 2002), due in part to its wide array of virulence factors that promote its growth and persistence within the host. One such virulence factor is the well-characterized exotoxin haemolytic phospholipase C (PlcH), which is secreted by P. aeruginosa when in association with eukaryotic hosts.…”

Section: Introductionmentioning

confidence: 99%

Global regulator Anr represses PlcH phospholipase activity in Pseudomonas aeruginosa when oxygen is limiting

et al. 2014

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Haemolytic phospholipase C (PlcH) is a potent virulence and colonization factor that is expressed at high levels by Pseudomonas aeruginosa within the mammalian host. The phosphorylcholine liberated from phosphatidylcholine and sphingomyelin by PlcH is further catabolized into molecules that both support growth and further induce plcH expression. We have shown previously that the catabolism of PlcH-released choline leads to increased activity of Anr, a global transcriptional regulator that promotes biofilm formation and virulence. Here, we demonstrated the presence of a negative feedback loop in which Anr repressed plcH transcription and we proposed that this regulation allowed for PlcH levels to be maintained in a way that promotes productive host-pathogen interactions. Evidence for Anr-mediated regulation of PlcH came from data showing that growth at low oxygen (1 %) repressed PlcH abundance and plcH transcription in the WT, and that plcH transcription was enhanced in an Danr mutant. The plcH promoter featured an Anr consensus sequence that was conserved across all P. aeruginosa genomes and mutation of conserved nucleotides within the Anr consensus sequence increased plcH expression under hypoxic conditions. The Anr-regulated transcription factor Dnr was not required for this effect. The loss of Anr was not sufficient to completely derepress plcH transcription as GbdR, a positive regulator of plcH, was required for expression. Overexpression of Anr was sufficient to repress plcH transcription even at 21 % oxygen. Anr repressed plcH expression and phospholipase C activity in a cell culture model for P. aeruginosa-epithelial cell interactions. INTRODUCTIONPseudomonas aeruginosa squanders few opportunities to colonize a vulnerable human host. In addition to engendering a range of nosocomial infections, including keratitis (Green et al., 2008), burn wounds (de Macedo & Santos, 2005), endocarditis (Baddour et al., 2005) and implanted medical devices (Hidron et al., 2008), it also colonizes the lungs of 80 % of persons with the heritable disease cystic fibrosis (CF) (Rajan & Saiman, 2002;Rosenfeld et al., 2003). Colonization by P. aeruginosa contributes to the decline of lung function in this patient population (Rajan & Saiman, 2002), due in part to its wide array of virulence factors that promote its growth and persistence within the host. One such virulence factor is the well-characterized exotoxin haemolytic phospholipase C (PlcH), which is secreted by P. aeruginosa when in association with eukaryotic hosts. PlcH is essential for virulence in co-culture with fungal filaments, on Arabidopsis leaves, in Galleria mellonella larvae and in mammalian hosts (Hogan & Kolter, 2002;Jander et al., 2000;Rahme et al., 2000), highlighting its importance in diverse models of infection.PlcH degrades the abundant phospholipids phosphatidylcholine (PC) and sphingomyelin, which are found in eukaryotic membranes and in lung surfactant (Berka & Vasil, 1982;Vasil, 2006). PC degradation releases both fatty acids and choline-containing c...

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Pulmonary infections in patients with cystic fibrosis

Cited by 210 publications

References 0 publications

Haemophilus influenzae and Haemophilus parainfluenza in Cystic Fibrosis: 15 Years Experience

Haemophilus influenzae and Haemophilus parainfluenza in Cystic Fibrosis: 15 Years Experience

Viral Respiratory Tract Infections in Cystic Fibrosis

Global regulator Anr represses PlcH phospholipase activity in Pseudomonas aeruginosa when oxygen is limiting

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