We measured the prevalence and temporal trends of pulmonary nontuberculous mycobacterial disease among residents of Ontario, Canada, during 1998–2010. Five-year prevalence increased from 29.3 cases/100,000 persons in 1998–2002 to 41.3/100,000 in 2006–2010 (p<0.0001). Improved laboratory methods did not explain this increase, suggesting a surge in disease prevalence.

A series of mutations at the highly solvent-exposed lysine 73 of iso-1-cytochrome c have been prepared by site-directed mutagenesis. These mutations were designed to probe denatured-state effects on the unfolding equilibrium of this protein. The hydrophilic amino acid Lys was replaced with the hydrophobic amino acids Met, Tyr, Phe, and Trp. The idea was to induce stabilizing hydrophobic interactions in the unfolded state, while having little effect on the folded-state energy due to the high solvent exposure of this site. Fourier transform infrared spectral analyses indicate that none of these mutations significantly affect the native fold of the protein. The stability of each protein to guanidine hydrochloride denaturation was monitored at 25 degrees C by circular dichroism spectroscopy. All four hydrophobic mutants decreased the value of delta Go uH2O, the free energy of unfolding of the protein in the absence of denaturant, by 1.0-1.5 kcal/mol. The delta Go uH2O values for these proteins correlate linearly (correlation coefficient of 0.98) with the hydrophobicity of the amino acid at position 73 of the sequence. These data are consistent with the idea that the position-73 mutants are more buried in the denatured state than in the native state, suggestive of a compact denatured state where such interactions would be possible.

BACKGROUND: The reported prevalence of pulmonary nontuberculous mycobacteria (NTM) infections is increasing.OBJECTIVE: To determine the ‘isolation prevalence’ of NTM in 2007 and compare it with previously published research that examined the increasing rates of isolation of NTM from clinical pulmonary specimens between 1997 and 2003.METHODS: Isolation prevalence was investigated retrospectively by reviewing a cohort of all positive pulmonary NTM culture results from the Tuberculosis and Mycobacteriology Laboratory, Public Health Laboratory (Toronto, Ontario) in 2007, which identifies at least 95% of NTM isolates in Ontario. Isolation prevalence was calculated as the number of persons with a pulmonary isolate in a calendar year divided by the contemporary population and expressed per 100,000 population. Changes in isolation prevalence from previous years were assessed for statistical significance using generalized linear models with a negative binomial distribution.RESULTS: In 2007, 4160 pulmonary isolates of NTM were collected from 2463 patients. The isolation prevalence of all species (excludingMycobacterium gordonae) was 19 per 100,000 population in 2007 – an increase from previous observations reported for Ontario – corresponding to an average annual increase of 8.5% from 1997 to 2007 (P<0.0001). Average annual increases in isolation prevalence ofMycobacterium aviumcomplex (8.8%, P<0.0001) andMycobacterium xenopi(7.3%, P=0.0005) were largely responsible for the overall increase, while prevalence rates of rapidly growing mycobacteria remained relatively stable.CONCLUSION: The isolation prevalence of pulmonary NTM continues to increase significantly in Ontario, supporting the belief that pulmonary NTM disease is increasingly common.

Women comprised a small majority with disease. Nodular bronchiectasis in women was most common, but significant proportions of each gender with each radiographic type were observed. NTM isolation, particularly MAC, was frequently associated with disease.

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