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Selective Sweeps and Parallel Pathoadaptation Drive Pseudomonas aeruginosa Evolution in the Cystic Fibrosis Lung.

Diaz Caballero J, Clark ST, Coburn B, Zhang Y, Wang PW, Donaldson SL, Tullis DE, Yau YC, Waters VJ, Hwang DM, Guttman DS - MBio (2015)

Bottom Line: Our functional analysis of these alleles shows that they provide differential fitness benefits dependent on the antibiotic under selection.Pseudomonas aeruginosa is a bacterial opportunistic pathogen responsible for significant morbidity and mortality in cystic fibrosis (CF) patients.We show that diversity of P. aeruginosa is driven by recurrent clonal emergence and expansion within this patient and identify potential adaptive variants associated with these events.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.

No MeSH data available.


Related in: MedlinePlus

Relationship between pbpB alleles and MICs to selected antipseudomonal antibiotics. Pseudomonas aeruginosa isolates were grouped by pbpB genotype based on the presence of major and minor alleles, as well as clade membership in clade A (ancestral) and clade B (sweep) populations. Antibiotic MICs were assayed for aztreonam (A), cefsulodin (B), ceftazidime (C), and piperacillin (D). The presence of the minor alleles was associated with significantly increased resistance to aztreonam and cefsulodin in both clades but to ceftazidime and piperacillin only for the clade A minor allele. Statistical significance was determined by Mann-Whitney U test and is indicated with asterisks. (**, P ≤ 0.01; ***, P ≤ 0.001).
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fig6: Relationship between pbpB alleles and MICs to selected antipseudomonal antibiotics. Pseudomonas aeruginosa isolates were grouped by pbpB genotype based on the presence of major and minor alleles, as well as clade membership in clade A (ancestral) and clade B (sweep) populations. Antibiotic MICs were assayed for aztreonam (A), cefsulodin (B), ceftazidime (C), and piperacillin (D). The presence of the minor alleles was associated with significantly increased resistance to aztreonam and cefsulodin in both clades but to ceftazidime and piperacillin only for the clade A minor allele. Statistical significance was determined by Mann-Whitney U test and is indicated with asterisks. (**, P ≤ 0.01; ***, P ≤ 0.001).

Mentions: We noted that aztreonam and piperacillin-tazobactam were first administered intravenously during the time that roughly coincides with the emergence of clade B (Fig. 1). Since aztreonam has high affinity for PBP3 (54), we examined the in vitro fitness of the clade A-derived pbpB allele, the most common clade B-derived pbpB allele, and the ancestral pbpB allele using standard MIC assays against four antipseudomonal β-lactam antibiotics (Fig. 6) (55). The ancestral allele is present in both clades but carried in different genetic backgrounds; nevertheless, the resistance it confers does not differ significantly among strains, regardless of their clade of origin (P = 0.15 to 0.44). The derived PBP3 alleles from both clades A and B increased strain resistance relative to the ancestral allele in the presence of both aztreonam and cefsulodin. In contrast, when tested on ceftazidime and piperacillin, while the clade A allele increased resistance, the clade B allele was no more resistant than the ancestral allele. These results indicate that the in vitro fitness contribution of each derived PBP3 allele (as measured by antibiotic resistance) is dependent on the specific antibiotic environment in which it is found.


Selective Sweeps and Parallel Pathoadaptation Drive Pseudomonas aeruginosa Evolution in the Cystic Fibrosis Lung.

Diaz Caballero J, Clark ST, Coburn B, Zhang Y, Wang PW, Donaldson SL, Tullis DE, Yau YC, Waters VJ, Hwang DM, Guttman DS - MBio (2015)

Relationship between pbpB alleles and MICs to selected antipseudomonal antibiotics. Pseudomonas aeruginosa isolates were grouped by pbpB genotype based on the presence of major and minor alleles, as well as clade membership in clade A (ancestral) and clade B (sweep) populations. Antibiotic MICs were assayed for aztreonam (A), cefsulodin (B), ceftazidime (C), and piperacillin (D). The presence of the minor alleles was associated with significantly increased resistance to aztreonam and cefsulodin in both clades but to ceftazidime and piperacillin only for the clade A minor allele. Statistical significance was determined by Mann-Whitney U test and is indicated with asterisks. (**, P ≤ 0.01; ***, P ≤ 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556809&req=5

fig6: Relationship between pbpB alleles and MICs to selected antipseudomonal antibiotics. Pseudomonas aeruginosa isolates were grouped by pbpB genotype based on the presence of major and minor alleles, as well as clade membership in clade A (ancestral) and clade B (sweep) populations. Antibiotic MICs were assayed for aztreonam (A), cefsulodin (B), ceftazidime (C), and piperacillin (D). The presence of the minor alleles was associated with significantly increased resistance to aztreonam and cefsulodin in both clades but to ceftazidime and piperacillin only for the clade A minor allele. Statistical significance was determined by Mann-Whitney U test and is indicated with asterisks. (**, P ≤ 0.01; ***, P ≤ 0.001).
Mentions: We noted that aztreonam and piperacillin-tazobactam were first administered intravenously during the time that roughly coincides with the emergence of clade B (Fig. 1). Since aztreonam has high affinity for PBP3 (54), we examined the in vitro fitness of the clade A-derived pbpB allele, the most common clade B-derived pbpB allele, and the ancestral pbpB allele using standard MIC assays against four antipseudomonal β-lactam antibiotics (Fig. 6) (55). The ancestral allele is present in both clades but carried in different genetic backgrounds; nevertheless, the resistance it confers does not differ significantly among strains, regardless of their clade of origin (P = 0.15 to 0.44). The derived PBP3 alleles from both clades A and B increased strain resistance relative to the ancestral allele in the presence of both aztreonam and cefsulodin. In contrast, when tested on ceftazidime and piperacillin, while the clade A allele increased resistance, the clade B allele was no more resistant than the ancestral allele. These results indicate that the in vitro fitness contribution of each derived PBP3 allele (as measured by antibiotic resistance) is dependent on the specific antibiotic environment in which it is found.

Bottom Line: Our functional analysis of these alleles shows that they provide differential fitness benefits dependent on the antibiotic under selection.Pseudomonas aeruginosa is a bacterial opportunistic pathogen responsible for significant morbidity and mortality in cystic fibrosis (CF) patients.We show that diversity of P. aeruginosa is driven by recurrent clonal emergence and expansion within this patient and identify potential adaptive variants associated with these events.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.

No MeSH data available.


Related in: MedlinePlus