Mucoid<i>Pseudomonas</i>in Cystic Fibrosis

Pritt, Bobbi S.; O'Brien, Linda; Winn, Washington C.

doi:10.1309/kjrpc7dd5tr9ntdm

Cited by 88 publications

(85 citation statements)

References 11 publications

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“…39 Mucoid conversion of P. aeruginosa in CF is associated with resistance to antibiotics and increased morbidity and mortality. 40 In the present study, which was not designed to address those questions, sex and the mucoid state of P. aeruginosa were not significant determinants of respiratory muscle function in CF subjects. The lack of statistical difference in P Imax between subjects infected with mucoid versus non-mucoid P. aeruginosa raises the question of whether muscle weakness is the result of the chronic disease itself rather than the P. aeruginosa infection state.…”

Section: Discussioncontrasting

confidence: 50%

ChronicPseudomonas aeruginosaInfection and Respiratory Muscle Impairment in Cystic Fibrosis

et al. 2013

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BACKGROUND: Chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is associated with increased morbidity. Chronic infection can cause limb and respiratory muscle compromise. Respiratory muscle function can be assessed via maximal inspiratory pressure (P Imax ), maximal expiratory pressure (P Emax ), and the pressure-time index of the respiratory muscles (PTI mus ). We studied the effect of chronic P. aeruginosa infection on respiratory muscle function in patients with CF. METHODS: This cross-sectional study assessed P Imax , P Emax , PTI mus , FEV 1 , FVC, maximum expiratory flow during the middle half of the FVC maneuver, body mass index, and upper arm muscle area in 122 subjects with CF, in 4 subgroups matched for age and sex at different stages of P. aeruginosa infection, according to the Leeds criteria. We compared respiratory muscle function in the subgroups according to P. aeruginosa infection state. RESULTS: Median P Imax was significantly lower in CF subjects with chronic P. aeruginosa infection (P Imax ‫؍‬ 62 cm H 2 O), compared to subjects who were never infected (P Imax ‫؍‬ 86 cm H 2 O, P ‫؍‬ .02), free of infection (P Imax ‫؍‬ 74 cm H 2 O, P ‫؍‬ .01), or intermittently infected (P Imax ‫؍‬ 72 cm H 2 O, P ‫؍‬ .02). Median PTI mus was significantly increased in CF subjects with chronic P. aeruginosa infection (PTI mus ‫؍‬ .142), compared to subjects who were free of infection (PTI mus ‫؍‬ .102, P ‫؍‬ .006). Median upper-arm muscle area was significantly lower in CF subjects with chronic P. aeruginosa infection (upper-arm muscle area ‫؍‬ 2,219 mm 2 ), compared to subjects who were never infected (2,754 mm 2 , P ‫؍‬ .03), free of infection (2,678 mm 2 , P ‫؍‬ .01), or intermittently infected (2,603 mm 2 , P ‫؍‬ .04). Multivariate logistic regression revealed P. aeruginosa state of infection as a significant determinant of PTI mus (P ‫؍‬ .03) independently of sex, upper-arm muscle area, and FEV 1 . CON-CLUSIONS: CF subjects with chronic P. aeruginosa infection exhibited impaired respiratory muscle function and decreased inspiratory muscle strength, and chronic P. aeruginosa infection independently impacts respiratory muscle function in subjects with CF.

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Section: Discussioncontrasting

confidence: 50%

ChronicPseudomonas aeruginosaInfection and Respiratory Muscle Impairment in Cystic Fibrosis

et al. 2013

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“…Presence of these autoantibodies in the bronchoalveolar lavage fluid of CF patients suggests that the autoimmune response might arise locally in the CF patient airway (Figure 5B). Moreover, incidence of anti-CTBPI IgG strongly associated with P. aeruginosa-positive sputum culture as well as with infection with the mucoid form of P. aeruginosa, which is associated with increased morbidity and mortality in CF ( Figure 5, C and D) (45). Furthermore, patients that were homozygous for the F508 deletion mutation (F508del) in CFTR had significantly lower levels of serum anti-nBPI IgG than CF patients with F508del heterozygosity or a different CFTR mutation ( Figure 5E).…”

Section: Resultsmentioning

confidence: 99%

The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

Skopelja¹,

Hamilton²,

Jones³

et al. 2016

JCI Insight

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“…Indeed, we show that phage Ab09 often selects for mutants with a mucoid phenotype, probably related to an increased capability to produce alginates. In the context of cystic fibrosis infection, mucoidy favours the formation of protected colonies with increased resistance to opsonization, phagocytosis and destruction by antibiotics (Pritt et al, 2007). It has been shown that alterations of a single band or both bands of the O-antigen of P. aeruginosa PAO1 can give rise to mutants with increased cytotoxicity mediated by the type III secretion system (Augustin et al, 2007).…”

Section: Cross-resistance and Reversibility Of Mutantsmentioning

confidence: 99%

Pseudolysogeny and sequential mutations build multiresistance to virulent bacteriophages in Pseudomonas aeruginosa

Latino

2016

Microbiology

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Coevolution between bacteriophages (phages) and their prey is the result of mutualistic interactions. Here, we show that pseudolysogeny is a frequent outcome of infection by virulent phages of Pseudomonas aeruginosa and that selection of resistant bacterial mutants is favoured by continuous production of phages. We investigated the frequency and characteristics of P. aeruginosa strain PAO1 variants resisting infection by different combinations of virulent phages belonging to four genera. The frequency of resistant bacteria was 10 25 for single phage infection and 10 26 for infections with combinations of two or four phages. The genome of 27 variants was sequenced and the comparison with the genome of the parental PAO1 strain allowed the identification of point mutations or small indels. Four additional variants were characterized by a candidate gene approach. In total, 27 independent mutations were observed affecting 14 genes and a regulatory region. The mutations affected genes involved in biosynthesis of type IV pilus, alginate, LPS and O-antigen. Half of the variants possessed changes in homopolymer tracts responsible for frameshift mutations and these phase variation mutants were shown to be unstable. Eleven double mutants were detected. The presence of free phage DNA was observed in association with exclusion of superinfection in half of the variants and no chromosomal mutation could be found in three of them. Upon further growth of these pseudolysogens, some variants with new chromosomal mutations were recovered, presumably due to continuous evolutionary pressure.

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MucoidPseudomonasin Cystic Fibrosis

Abstract: A b s t r a c t

Cited by 88 publications

References 11 publications

ChronicPseudomonas aeruginosaInfection and Respiratory Muscle Impairment in Cystic Fibrosis

ChronicPseudomonas aeruginosaInfection and Respiratory Muscle Impairment in Cystic Fibrosis

The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

Pseudolysogeny and sequential mutations build multiresistance to virulent bacteriophages in Pseudomonas aeruginosa

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