Clinical characteristics and outcomes associated with Inquilinus infection in cystic fibrosis.

BACKGROUND: Molecular diagnostics have led to the identification of a broad range of bacterial species in cystic fibrosis (CF) including Inquilinus. The clinical significance of Inquilinus in CF has not been thoroughly characterized. METHODS: Retrospective, case-control study of persons with CF from two CF centers with at least one respiratory culture positive for Inquilinus spp. compared with age-matched CF controls with chronic Pseudomonas aeruginosa. Percent predicted forced expiratory volume in one second (ppFEV1) and body mass index percentile (BMI) were modeled from time of first positive culture up to 5 years later. Rates of pulmonary exacerbations were compared. Inquilinus isolates were genotyped to evaluate strain diversity. RESULTS: Seventeen patients with Inquilinus infection were identified with a mean age of 13 years at first positive culture. Most cases had multiple cultures positive for Inquilinus. ppFEV1 was not different between cases versus controls (80.2% vs 81.6%, p = 0.97 at baseline, 67.5% vs. 73.3%, p = 0.82 at 5 years). Patients were undernourished and BMI percentiles did not differ between groups (30.7% vs 43.4%, p = 0.32 at baseline, 37.9% vs. 37.6%, p = 0.98 at 5 years). There was no difference in the pulmonary exacerbation rate (3.0/year vs 2.5/year, p = 0.34). Genotyping showed diverse genetic strains between patients. CONCLUSIONS: Inquilinus can present in childhood and is often associated with chronic infection in CF. Lung function and nutrition status at time of detection, lung function decline, and pulmonary exacerbation rates in Inquilinus cases were similar to those with chronic P. aeruginosa, a well-established CF pathogen.

Potential pathogenicity of Inquilinus limosus in a pediatric patient with cystic fibrosis.

PRESENTATION: Patient is a 6-year-old male with CF, MRSA colonization, and pancreatic insufficiency that presented with worsening ppFEV1 and systemic symptoms despite multiple interventions. BAL grew NTM, Stenotrophomonas maltophilia, and Inquilinus limosus, a rare organism found in patients with CF. COURSE: I. limosus treatment was deferred. Despite treatment of other pathogens, symptoms worsened. I. limosus was targeted with meropenem, amikacin, and ciprofloxacin along with clindamycin for MRSA colonization. Within weeks, symptoms had resolved with ppFEV1 improvement. DISCUSSION: This case discusses the importance of a rare organism in the CF population. Targeting I. limosus was key to recovery, revealing its potential pathogenicity.

Conformational properties of two exopolysaccharides produced by Inquilinus limosus, a cystic fibrosis lung pathogen.

Inquilinus limosus is a multi-resistant bacterium found in the respiratory tract of patients with cystic fibrosis. This bacterium produces two unique fully pyruvylated exopolysaccharides in similar quantities: an α-(1→2)-linked mannan and a ß-(1→3)-linked glucan. We employed molecular modelling methods to probe the characteristic conformations and dynamics of these polysaccharides, with corroboration from potentiometric titrations and circular dichroism experiments. Our calculations reveal different structural motifs for the mannan and glucan polysaccharides: the glucan forms primarily right-handed helices with a wide range of extensions, while the mannan forms only left-handed helices. This finding is supported by our circular dichroism experiments. Our calculations also show that the (1→3)-ß-d-Glcp linkage is more dynamically flexible than the (1→2)-α-d-Manp: the glucan characteristically forms a range of wide helices with large central cavities. In contrast, the mannan forms rigid regular 'bottlebrush' helices with a minimal central cavity. The widely different character of these two polymers suggests a possible differentiation of biological roles.

Exopolysaccharides produced by Inquilinus limosus, a new pathogen of cystic fibrosis patients: novel structures with usual components.

The major cause of morbidity and mortality in patients with cystic fibrosis, an autosomal recessive disorder, is chronic microbial colonisation of the major airways that leads to exacerbation of pulmonary infection. Several different microbes colonise cystic fibrosis lungs, and Pseudomonas aeruginosa is one of the most threatening, since the establishment of mucoid (alginate producing) strains is ultimately associated with the patient's death. Very recently a new bacterium, named Inquilinus limosus, was repeatedly found infecting the respiratory tract of cystic fibrosis patients. Its multi-resistance characteristic to antibiotics might result in the spreading of I. limosus infection among the cystic fibrosis community, as recently happened with strains of the Burkholderia cepacia complex. Since exopolysaccharides are recognised as important virulence factors in lung infections, the primary structure of the polysaccharide produced by I. limosus strain LMG 20952(T) was investigated as the first step in understanding its role in pathogenesis. The structure was determined by means of methylation analysis, acid degradations, mass spectrometry and NMR spectroscopy. The results showed that the bacterium produced a mixture constituted of the following polymers: [3)-[4,6-O-(1-carboxyethylidene)]-beta-D-Glcp(1-->]n; [2)-[4,6-O-(1-carboxyethylidene)]-alpha-D-Manp(1-->]n. Both polymers were completely substituted with pyruvyl ketal groups, a novel structural characteristic not previously found in bacterial polysaccharides. The absolute configuration of all pyruvyl groups was S. Inspection of possible local conformations assumed by the two polysaccharide chains showed features, which might provide interesting clues for understanding structure-function relationships.