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10.1016/j.chom.2015.07.006

http://scihub22266oqcxt.onion/10.1016/j.chom.2015.07.006
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C4589543!4589543!26299432
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suck abstract from ncbi


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pmid26299432      Cell+Host+Microbe 2015 ; 18 (3): 307-19
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  • Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs #MMPMID26299432
  • Jorth P; Staudinger BJ; Wu X; Hisert K; Hayden H; Garudathri J; Harding C; Radey MC; Rezayat A; Bautista G; Barrington W; Goddard AF; Zheng C; Angermeyer A; Brittnacher MJ; Kitzman J; Shendure J; Fligner CL; Mittler J; Aitken ML; Manoil C; Bruce JE; Yahr TL; Singh PK
  • Cell Host Microbe 2015[Sep]; 18 (3): 307-19 PMID26299432show ga
  • Bacterial lineages that chronically infect cystic fibrosis (CF) patients genetically diversify during infection. However, the mechanisms driving diversification are unknown. By dissecting 10 CF lung pairs and studying ~12,000 regional isolates, we were able to investigate whether clonally-related Pseudomonas aeruginosa inhabiting different lung regions evolve independently and differ functionally. Phylogenetic analysis of genome sequences showed that regional isolation of P. aeruginosa drives divergent evolution. We investigated the consequences of regional evolution by studying isolates from mildly and severely-diseased lung regions and found evolved differences in bacterial nutritional requirements, host-defense and antibiotic resistance, and virulence due to hyperactivity of type 3 secretion systems. These findings suggest that bacterial intermixing is limited in CF lungs, and that regional selective pressures may markedly differ. The findings also may explain how specialized bacterial variants arise during infection, and raise the possibility that pathogen diversification occurs in other chronic infections characterized by spatially heterogeneous conditions.
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