Intraclonal genome diversity of the major <i>Pseudomonas aeruginosa</i> clones <scp>C</scp> and <scp>PA</scp>14

Fischer, Sebastian; Klockgether, Jens; Losada, Patricia Morán; Chouvarine, Philippe; Cramer, Nina; Davenport, Colin; Dethlefsen, Sarah; Dorda, Marie; Goesmann, Alexander; Hilker, Rolf; Mielke, S.; Schönfelder, Torben; Suerbaum, Sebastian; Türk, Oliver; Woltemate, Sabrina; Wiehlmann, Lutz; Tümmler, Burkhard

doi:10.1111/1758-2229.12372

Cited by 38 publications

(58 citation statements)

References 31 publications

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“…Nonsynonymous SNPs present in the pangenome were less frequent among SNPs (N/S ϭ 0.13; P ϭ 2.5 ϫ 10 Ϫ5 by Fisher's exact test) than expected from the N/S ratio of 0.23 derived from whole-genome sequence comparisons (27), whereas nonsynonymous SNPs were overrepresented among the SNPs not known from the pangenome analysis (N/S ϭ 0.58; P ϭ 2.1 ϫ 10 Ϫ21 ). These data indicate that changes in the coding sequences of targets of antimicrobials are normally counterselected because these genes are probably essential for P. aeruginosa.…”

Section: Resultsmentioning

confidence: 84%

“…The emergence of a premature termination codon will result in most cases in the loss of protein function, unless some translational read-through is promoted. The sequencing of an individual 6-to 7-Mbp large P. aeruginosa genome will typically identify one or two stop mutations (24,27). Amplicon sequencing of the 361 CF isolates in the 17 loci uncovered a significantly higher rate of stop mutations.…”

Section: Resultsmentioning

confidence: 99%

“…Fragment libraries were prepared at the E120 scale according to the protocols provided by Thermo Life Technologies (LT) for SOLiD 5500XL instruments. These standard protocols generate a bias for GC-rich sequences, as the ligation of the adaptors becomes inefficient for DNA fragments containing more than 65% GC (27), which are common for P. aeruginosa with its average genomic GC content of 67%. To compensate for this constraint, we modified the ligation step of the standard protocol (LT).…”

Section: Methodsmentioning

confidence: 99%

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Molecular Epidemiology of Mutations in Antimicrobial Resistance Loci of Pseudomonas aeruginosa Isolates from Airways of Cystic Fibrosis Patients

Greipel

Fischer

Klockgether

et al. 2016

Antimicrob Agents Chemother

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bThe chronic airway infections with Pseudomonas aeruginosa in people with cystic fibrosis (CF) are treated with aerosolized antibiotics, oral fluoroquinolones, and/or intravenous combination therapy with aminoglycosides and ␤-lactam antibiotics. An international strain collection of 361 P. aeruginosa isolates from 258 CF patients seen at 30 CF clinics was examined for mutations in 17 antimicrobial susceptibility and resistance loci that had been identified as hot spots of mutation by genome sequencing of serial isolates from a single CF clinic. Combinatorial amplicon sequencing of pooled PCR products identified 1,112 sequence variants that were not present in the genomes of representative strains of the 20 most common clones of the global P. aeruginosa population. A high frequency of singular coding variants was seen in spuE, mexA, gyrA, rpoB, fusA1, mexZ, mexY, oprD, ampD, parR, parS, and envZ (amgS), reflecting the pressure upon P. aeruginosa in lungs of CF patients to generate novel protein variants. The proportion of nonneutral amino acid exchanges was high. Of the 17 loci, mexA, mexZ, and pagL were most frequently affected by independent stop mutations. Private and de novo mutations seem to play a pivotal role in the response of P. aeruginosa populations to the antimicrobial load and the individual CF host. C ystic fibrosis (CF) is a severe autosomal recessive trait that is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) (1). CFTR dysfunction affects many organs, but lung disease is responsible for the vast majority of morbidity and mortality in people with CF. The basic defect in CF predisposes to viral and bacterial airway infections (2). The most prevalent airway pathogen in adolescents and adults with CF is Pseudomonas aeruginosa (3, 4). The chronic airway colonization with P. aeruginosa has been associated with a rapid decline in lung function, heightened lung inflammation, and worse prognosis (1).Antipseudomonal chemotherapy in CF comprises intravenous combination therapy with ␤-lactam antibiotics and aminoglycosides, oral fluoroquinolones, immunomodulatory treatment with azithromycin and aerosolized antibiotics such as tobramycin, aztreonam, or colistin (4-8). The high antimicrobial pressure exerted on the microorganism, which can persist and diversify in the patient's airways for decades, drives the emergence of drug resistance phenotypes (9, 10). Typical targets are elements of replication, transcription, and translation, the cell wall, and transport and its regulation (9-11).During ongoing studies on the long-term microevolution of P. aeruginosa in lungs of 12 CF patients, we have identified 17 loci to be repetitively hit by mutations. These loci are known from the literature to be associated with the emergence of drug resistance in P. aeruginosa (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Hence, we became interested to know if and to what extent the global P. aeruginosa population in lungs of patients (CF lungs) carries mutations in these ge...

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Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Molecular Epidemiology of Mutations in Antimicrobial Resistance Loci of Pseudomonas aeruginosa Isolates from Airways of Cystic Fibrosis Patients

Greipel

Fischer

Klockgether

et al. 2016

Antimicrob Agents Chemother

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“…Finally, 100 genome sequences of P. aeruginosa clone C and clone PA14 isolates were sequenced on a SOLiD 5500XL system with a 75‐bp read length. Reads were aligned to PAO1 reference genome using the program novoaligncs (http://www.novocraft.com).…”

Section: Methodsmentioning

confidence: 99%

Three‐base periodicity of sites of sequence variation in Pseudomonas aeruginosa and Staphylococcus aureus core genomes

et al. 2016

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The three-base periodicity property is characteristic of protein-coding sequences. Here, we report on three-base periodicity of sequence variation in the core genome of bacteria. Single nucleotide polymorphism (SNP) syntenies were extracted from pairwise genome alignments of 41 Staphylococcus aureus or 20 Pseudomonas aeruginosa strains. The length of fragment pairs with identical nucleotides at all SNP positions showed a length-dependent overrepresentation of multiples of three nucleotides at corresponding codon positions of the AT-rich S. aureus and the GC-rich P. aeruginosa. Three-base SNP periodicity seems to be a characteristic feature of the tightly arranged bacterial core genome.

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“…Therefore, recent studies have suggested that there must be some mechanism for gene loss to counterbalance these gene acquisitions [2,3]. Furthermore, several studies have shown that most of these imported genomic regions usually come from closely-related genomes but the precise origin cannot be identified [1,[4][5][6]. Therefore, it has been difficult to perform detailed analyses of the recombination processes that result in the acquisition of new genes via naturally occurring horizontal gene transfer (HGT).…”

Section: Introductionmentioning

confidence: 99%

Recombination and gene loss occur simultaneously during bacterial horizontal gene transfer

Ely¹

2020

PLoS ONE

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Bacteria can acquire new genes by incorporating environmental DNA into their genomes, yet genome sizes stay relatively constant. In nature, gene acquisition is a rare event so it is difficult to observe. However, the Caulobacter crescentus CB2A genome contains 114 insertions of genetic material from the closely-related NA1000 strain, providing a unique opportunity to analyze the horizontal transfer of genetic material. Analyses of these insertions led to a new model that involves preferential recombination at non-homologous regions that are flanked by regions of homology and does not involve any mutational processes. The net result is the replacement of segments of the recipient genome instead of the simple addition of genetic material during horizontal gene transfer. Analyses of the genomes of closely related strains of other bacterial and archaea genera, suggested that horizontal gene transfer occurs preferentially in non-homologous regions in these organisms as well. Thus, it appears to be a general phenomenon that prokaryotic horizontal gene transfer occurs preferentially at sites where the incoming DNA contains a non-homologous region that is flanked by regions of homology. Therefore, gene replacement is a common phenomenon during horizontal gene transfer.

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Intraclonal genome diversity of the major Pseudomonas aeruginosa clones C and PA14

Cited by 38 publications

References 31 publications

Molecular Epidemiology of Mutations in Antimicrobial Resistance Loci of Pseudomonas aeruginosa Isolates from Airways of Cystic Fibrosis Patients

Molecular Epidemiology of Mutations in Antimicrobial Resistance Loci of Pseudomonas aeruginosa Isolates from Airways of Cystic Fibrosis Patients

Three‐base periodicity of sites of sequence variation in Pseudomonas aeruginosa and Staphylococcus aureus core genomes

Recombination and gene loss occur simultaneously during bacterial horizontal gene transfer

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