Taylor, Rowena Frances Halstead; (1995) Microbiological aspects of infection with Pseudomonas aeruginosa in patients with cystic fibrosis. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Pseudomonas aeruginosa is seldom eradicated from the sputum of patients with cystic fibrosis (CF). This thesis examines two mechanisms which may contribute to its persistence. Having speculated that P. aeruginosa persists by adaptation to the CF mucosal environment, growth requirements of isolates from patients with CF and non-CF bronchiectasis were compared with each other and with isolates from other sources. Auxotrophs are bacterial mutants which require additional growth factors to those of the wild-type of the species (prototrophs). For the first time, auxotrophy of P. aeruginosa in CF and non-CF bronchiectasis has been demonstrated and auxotrophic isolates of P. aeruginosa were detected in the sputum of 92% of CF patients. Auxotrophs predominated in the sputum of patients with acute exacerbations and those with severe lung disease and were shown to be more resistant to anti-pseudomonal agents than prototrophs. Auxotrophic and prototrophic isolates were shown to be isogenic, and as methionine was identified as a growth factor for P. aeruginosa in 44% of patients, the possibility of inhibition of microbial methionine synthesis, acting synergistically with conventional agents may be explored in the future. The question of whether extra-pulmonary sites of P. aeruginosa exist and form reservoirs which may re-seed the lungs and perpetuate infection was addressed. The upper airways of 42 CF adults were assessed and 94% of patients with P. aeruginosa in the sputum were found to have reservoirs of the organism in their upper airways. When genotyped, strains from these sites were identical to those from the lungs, raising the possibility of a microbiological association between these sites. These results are particularly relevant to patients undergoing lung transplantation in view of the risk of infection from the upper airways contaminating the transplanted lungs. Also, awareness of these sites may advance epidemiological studies of the acquisition of P. aeruginosa in CF.

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