Auxotrophy of Pseudomonas aeruginosa in cystic fibrosis

Abstract

Seventy-four of 403 (18.4%) sputum isolates of Pseudomonas aeruginosa from 49 of 136 (36.0%) adults with cystic fibrosis (CF) were auxotrophic mutants. Two of 11 (18.2%) isolates of P. aeruginosa taken from patients with non-CF bronchiectasis were also auxotrophic. All 99 strains taken from non-bronchiectatic sources were prototrophic. Forty-six of 55 (83.6%) CF auxotrophs required one or more of 36 growth factors tested; the requirements for the remaining 9 isolates were not identified. Methionine was the sole factor required by 17 of 22 (77.3%) isolated which depended on a single factor. We conclude that auxotrophy is a feature of P. aeruginosa infection in cystic fibrosis.

The high amino-acid content of sputum from cystic fibrosis patients promotes growth of auxotrophic Pseudomonas aeruginosa

“…Although rare in other diseases, auxotrophy is a common phenomenon among bacteria colonising CF patients [5,18,191. Earlier studies demonstrated that the auxotrophic variants of P aeruginosa and Burkholderia cepacia were derived from the prototrophic wild-type strains [6,191 but the mechanism of selection of these forms in vivo remains obscure.…”

“…This adaptability extends to the nutritional status of the organism with many strains of E! aeruginosa from CF exhibiting auxotrophy for amino acids [5]. These variants are derived, in the lung, from prototrophic nutritionally efficient wild-type strains [6].…”

Essential genome of Pseudomonas aeruginosa in cystic fibrosis sputum

“…These results are consistent with findings that after long-term colonization of the CF lung many P. aeruginosa strains arise that are unable to biosynthesize particular amino acids (referred to as auxotrophs). Notably, the most common auxotrophs observed are for methionine, leucine, and arginine (7,29,30), which are amino acids deemed available by our analysis. Nutrients for which >95% of the biosynthetic genes contribute to fitness in both MOPSsputum and MOPS-succinate equally were deemed to be "not available."…”

Chronic pulmonary pseudomonal infection in patients with cystic fibrosis: A model for early phase symbiotic evolution

“…The concept of bacterial symbiosis in CF airway infection is strongly supported by the long-standing observation that pseudomonal auxotrophic strains can be found in 33-86% CF patients (Barth & Pitt, 1996;Haussler et al, 1999;Hoboth et al, 2009;Hogardt et al, 2007;Oberhardt et al, 2010;Taylor et al, 1992;Thomas et al, 2000). This metabolic divergence associated with CF Pa demonstrates that lifestyle changes are not limited to bacteria-to-bacteria interactions, but also bacteria-to-host associations.…”

“…Other emerging features associated with the adapting CF Pa are more perplexing and include: i) the evolution of slow-growing auxotrophic strains from initially rapidly-growing prototrophic strains; ii) the rise of mutations in virulence determinants from highly virulent wild-type strains; and iii) the emergence of antibiotic hyper-susceptible strains from antibiotic resistant parental strains (Figures 1 and 2) (Agarwal et al, 2005;Barth et al, 1998;Feary et al, 1969;Haussler et al, 1999;Hoboth et al, 2009;Hogardt et al, 2007;Qin et al, 2012;Starkey et al, 2009;Taylor et al, 1992;Thomas et al, 2000;Yang et al, 2008). Moreover, the prototrophic and auxotrophic isogenic strains together show high density growth both in vitro and in vivo, and display variable growth properties and antimicrobial susceptibilities, irrespective of their specific nutrient requirements (Palmer et al, 2007;Qin et al, 2012).…”