P. aeruginosa mutational resistome
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ABSTRACT:
PROVIDER: PRJEB24151 | ENA |
REPOSITORIES: ENA
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Project description:PSEUDOMONAS AERUGINOSA CYSTIC FIBROSIS MUTATIONAL RESISTOME CC274
| PRJEB19788 | ENA
Project description:Surfing motility is a novel form of surface adaptation exhibited by the nosocomial pathogen, Pseudomonas aeruginosa, in the presence of the glycoprotein mucin that is found in high abundance at mucosal surfaces especially the lungs of cystic fibrosis and bronchiectasis patients. Here we investigated the adaptive antibiotic resistance of P. aeruginosa under conditions in which surfing occurs compared to cells undergoing swimming. P. aeruginosa surfing cells were significantly more resistant to several classes of antibiotics including aminoglycosides, carbapenems, polymyxins, and fluroquinolones. This was confirmed by incorporation of antibiotics into growth medium, which revealed a concentration-dependent inhibition of surfing motility that occurred at concentrations much higher than those needed to inhibit swimming. To investigate the basis of resistance, RNA-Seq was performed and revealed that surfing influenced the expression of numerous genes. Included amongst genes dysregulated under surfing conditions were multiple genes from the Pseudomonas resistome, which are known to affect antibiotic resistance when mutated. Screening transposon mutants in these surfing-dysregulated resistome genes revealed that several of these mutants exhibited changes in susceptibility to one or more antibiotics under surfing conditions, consistent with a contribution to the observed adaptive resistance. In particular, several mutants in resistome genes, including armR, recG, atpB, clpS, nuoB, and certain hypothetical genes such as PA5130, PA3576 and PA4292, showed contributions to broad-spectrum resistance under surfing conditions and could be complemented by their respective cloned genes. Therefore, we propose that surfing adaption led to extensive multidrug adaptive resistance as a result of the collective dysregulation of diverse genes.
2018-06-26 | GSE110044 | GEO
Project description:In this study we have profiled a clinical tobramycin resistant P. aeruginosa strain that exhibited a small colony variant (SCV) phenotype. Both, the resistance and the colony morphology phenotypes were lost upon passaging the isolate under rich medium conditions. Transcriptional and mutational profiling revealed that the SCV harbored activating mutations in the two two-component systems AmgRS and PmrAB. Introduction of these mutations singularly into the type strain PA14 conferred tobramycin and colistin resistance, respectively. However, their combined introduction had an additive effect on the tobramycin resistance phenotype. Activation of the AmgRS system slightly reduced the colony size of the PA14 wild-type, whereas the simultaneous overexpression of gacA, the response regulator of the GacSA two component system, further reduced colony size. In conclusion, we uncovered combinatorial influences of two-component systems on clinically relevant phenotypes, such as resistance and the expression of the SCV phenotype. Our results clearly demonstrate that combined activation of P. aeruginosa two-component systems exhibit pleiotropic effects with unforeseen consequences.
2017-08-22 | GSE99729 | GEO
Project description:Emergence of epidemic clones and antibiotic resistance development compromises the management of Pseudomonas aeruginosa cystic fibrosis (CF) chronic respiratory infections. Whole genome sequencing (WGS) was used to decipher the phylogeny, interpatient dissemination, WGS mutator genotypes (mutome) and resistome of a widespread clone (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. The coexistence of two divergent CC274 clonal lineages was revealed, but without evident geographical barrier; phylogenetic reconstructions and mutational resistome demonstrated the interpatient transmission of mutators. The extraordinary capacity of P. aeruginosa to develop resistance was evidenced by the emergence of mutations in >100 genes related to antibiotic resistance during the evolution of CC274, catalyzed by mutator phenotypes. While the presence of classical mutational resistance mechanisms was confirmed and correlated with resistance phenotypes, results also showed a major role of unexpected mutations. Among them, PBP3 mutations, shaping up ?-lactam resistance, were noteworthy. A high selective pressure for mexZ mutations was evidenced, but we showed for the first time that high-level aminoglycoside resistance in CF is likely driven by mutations in fusA1/fusA2, coding for elongation factor G. Altogether, our results provide valuable information for understanding the evolution of the mutational resistome of CF P. aeruginosa.
| S-EPMC5514035 | biostudies-literature
Project description:Bacterial community and resistome of lettuce plants
| PRJEB36754 | ENA
Project description:Inhaled administration of high doses of aminoglycosides is a key maintenance treatment of Pseudomonas aeruginosa chronic respiratory infections in cystic fibrosis (CF). We analyzed the dynamics and mechanisms of stepwise high-level tobramycin resistance development in vitro and compared the results with those of isogenic pairs of susceptible and resistant clinical isolates. Resistance development correlated with fusA1 mutations in vitro and in vivo. pmrB mutations, conferring polymyxin resistance, were also frequently selected in vitro In contrast, mutational overexpression of MexXY, a hallmark of aminoglycoside resistance in CF, was not observed in in vitro evolution experiments.
| S-EPMC5913951 | biostudies-literature
Project description:Antibiotic resistome in Swiss river streams.
| PRJEB39697 | ENA
Project description:Transcript abundance was measured in whole-body virgin male Drosophila serrata from 41 inbred lines that had diverged through 27 generations of mutation accumulation. Pleiotropic mutations are the ultimate source of genetic variation in complex traits, including many human diseases. However, the nature and extent of mutational pleiotropy remain largely unknown. Here, we investigate the variation in 11,604 gene expression traits among 41 mutation accumulation lines of Drosophila serrata, which had diverged for 27 generations. We detected significant mutational variance in 4.6% of ESTs, but 70% of ESTs were invariant among lines, allowing us to reject a null hypothesis of phenome-wide universal pleiotropy. Mutational covariance among ESTs was detected at a frequency of only 1 in 193 random pairs of variable EST, bu t was detected among random combinations of five ESTs in 1 in 5 cases, revealing that mutational covariance among multiple ESTs was common. The observed frequency of significant multivariate covariance among random ESTs implied that a substantial number of ESTs (>70) must be pleiotropically affected by at least some mutations. We measured gene expression of male Drosophila serrata from 41 mutation accumulation lines (whole-body). Data from two replicates for each line are presented.
2013-09-01 | E-GEOD-49815 | biostudies-arrayexpress
Project description:Transcriptional and mutational profiling of an aminoglycoside resistant Pseudomonas aeruginosa small colony variant
| PRJNA389442 | ENA