Source: http://www.asmscience.org/content/book/10.1128/9781555815639.ch36
Timestamp: 2019-04-26 10:33:56+00:00

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This chapter focuses on the analysis of the factors driving the evolutive transition of Pseudomonas aeruginosa populations from the acute to the chronic infection scenario and the underlying consequences in terms of virulence, persistence (adaptation), and antimicrobial resistance. The transcendence of P. aeruginosa biofilms in the persistence of chronic infections demonstrates both its increased resistance to the host defense mechanisms, including the mechanical clearance and that mediated by complement, antibodies, or phagocytes, and its increased resistance to the antimicrobials action, reported to be over 100-fold higher than in planktonic cells. A nice example of how mutator cells can be amplified in a bacterial population by hitchhiking with adapting mutations was provided by Mao et al. In this work it was found that when E. coli populations are subjected to a one-step mutation selection process, hypermutable variants were amplified in the population from approximately 0.001 to 0.5%, and when they were subjected to two consecutive steps of mutants selection, the amplification reached 25 to 100%. A link between P. aeruginosa hypermutation and antibiotic resistance has also been documented for other chronic infections such as those occurring in patients with bronchiectasis or chronic obstructive pulmonary disease (COPD). The establishment of P. aeruginosa chronic infections is the result of a complex adaptation process that includes both physiological and genetic changes, ultimately leading to the selection of highly persistent bacterial populations.
Model of the sequential adaptive process for long-term persistence taking place in P. aeruginosa chronic lung infections.
(A) Imipenem (8 μg/ml) killing-kinetics for strain PAO1 and its hypermutable derivative PAOΔmutS. PAO1 is represented by dashed lines, and PAOΔmutS by full lines, squares indicate strains grown in Müller-Hinton broth without antibiotic, and diamonds indicate strains grown in 8 μg/ml imipenem Müller-Hinton broth. Displayed data were obtained from Ventre et al., 2006. (B) Imipenem Etest and disk diffusion susceptibility tests of strains PAO1 and PAOΔmutS showing the presence of RMS for the hypermutable strain.
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