More on Cystic Fibrosis and Pseudomonas infection

http://www.ncbi.nlm.nih.gov/pubmed/21930755

Infect Immun. 2011 Sep 19. [Epub ahead of print]
Genotypic and phenotypic variation in P. aeruginosa reveals signatures of secondary infection and mutator activity in certain CF patients with chronic lung infections.
Warren AE, Boulianne-Larsen CM, Chandler CB, Chiotti K, Kroll E, Miller SR, Taddei F, Sermet-Gaudelus I, Ferroni A, McInnerney K, Franklin MJ, Rosenzweig F.
Source
Division of Biological Sciences, The University of Montana, Missoula, Montana.

Abstract
Evolutionary adaptation of Pseudomonas aeruginosa to the cystic fibrosis lung is limited by genetic variation, which depends on rates of horizontal gene transfer and mutation supply. Because each may increase following secondary infection or mutator emergence we sought to ascertain incidence of secondary infection and genetic variability in populations containing or lacking mutators. Forty-nine strains collected over three years from sixteen patients were phenotyped for antibiotic resistance and mutator status, and genotyped by rep-PCR, PFGE, and MLST. Though phenotypic and genetic polymorphisms were widespread and clustered more strongly within rather than between longitudinal series, their distribution revealed instances of secondary infection. Sequence data, however, indicated that inter-lineage recombination predated initial strain isolation. Mutator series were more likely to be multiply antibiotic-resistant, but not necessarily more variable in their nucleotide sequences than non-mutators. One mutator and one non-mutator series were sequenced at mismatch repair loci and analyzed for gene content using DNA microarrays. Both were wild-type with respect to mutL, but mutators encoded an 8-bp mutS deletion causing a frameshift mutation. Both series lacked 126 genes encoding pilins, siderophores and virulence factors whose inactivation has been linked to adaptation during chronic infection. Mutators exhibited loss of several-fold more genes having functions related to mobile elements, motility and attachment. A 105kb, 86-gene deletion was observed in one non-mutator that resulted in loss of virulence factors related to pyoverdine synthesis and elements of the multi-drug efflux regulon. Diminished DNA repair activity may facilitate but not be absolutely required for rapid evolutionary change.