What It Takes to Be a Pseudomonas aeruginosa? The Core Genome of the Opportunistic Pathogen Updated

Valot, Benoı̂t; Guyeux, Christophe; Rolland, Julien Yves; Mazouzi, Kamel; Bertrand, Xavier; Hocquet, Didier

doi:10.1371/journal.pone.0126468

Cited by 99 publications

(85 citation statements)

References 47 publications

(61 reference statements)

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“…In contrast, our pan-and core genome sizes are significantly different from recent findings by Freschi et al (2019) [19] where the panand core genomes were 54,272 and 665 genes, respectively. By re-analysis of the dataset from Freschi et al with both our (GenAPI) and original (SaturnV) method, we show that the difference in pan-and core genome sizes can largely be ascribed to differences in bioinformatics analyses as pan-and core genome sizes from Freschi et al converge towards findings from this and other studies [34,35,36,37] when we re-analyzed the data with GenAPI. We have previously compared tools SaturnV and GenAPI [15], and we suggest that the relatively small size of the core genome reported by Freschi et al (665 genes) is due to false negative calls on genes with incomplete assemblies [38].…”

Section: Core Genome Snp Distances To Define Clone Typessupporting

confidence: 62%

Gene loss and acquisition in lineages of bacteria evolving in a human host environment

Gabrielaitė

Molin

et al. 2020

Preprint

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While genome analyses have documented that there are differences in the gene repertoire between evolutionary distant lineages of the same bacterial species, less is known about micro-evolutionary dynamics of gene loss and acquisition within lineages of bacteria as they evolve over the timescale of years. This knowledge is valuable to understand both the basic mutational steps that on long timescales lead to evolutionary distant bacterial lineages, and the evolution of the individual lineages themselves.In the case that lineages evolve in a human host environment, gene loss and acquisition may furthermore have implication for disease.We analyzed the genomes of 45 Pseudomonas aeruginosa lineages evolving in the lungs of cystic fibrosis patients to identify genes that are lost or acquired during the first years of infection in each of the different lineages. On average, the lineage genome content changed with 88 genes (range 0-473). Genes were more often lost than acquired, and prophage genes were more variable than bacterial genes. We identified genes that were lost or acquired independently across different clonal lineages, i.e. convergent molecular evolution. Convergent evolution suggests that there is a selection for loss and acquisition of certain genes in the host environment. We find that a significant proportion of such genes are associated with virulence; a trait previously shown to be important for adaptation. Furthermore, we also compared the genomes across lineages to show that within-lineage variable genes more often belonged to genomic content not shared across all lineages. Finally, we used 4,760 genes shared by 446 P. aeruginosa genomes to develop a stable and discriminatory typing scheme for P. aeruginosa clone types (Pactyper, https://github.com/MigleSur/Pactyper). In sum, our analysis adds to the knowledge on the pace and drivers of gene loss and acquisition in bacteria evolving over multiple years in a human host environment 3 and provides a basis to further understand how gene loss and acquisition plays a role in lineage differentiation and host adaptation.

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Section: Core Genome Snp Distances To Define Clone Typessupporting

confidence: 62%

Gene loss and acquisition in lineages of bacteria evolving in a human host environment

Gabrielaitė

Molin

et al. 2020

Preprint

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“…Thus, the phenotypic variability of strains cannot be solely attributed to significant proteincoding sequence variability (3). The highly conserved core genome represents 88% of the average P. aeruginosa genome (4). Genes involved in aerobic and anaerobic respiration, transcription and translation regulation, DNA and protein repair, hydrocarbon degradation, and multidrug efflux systems are all represented in the core genome.…”

mentioning

confidence: 99%

Transcriptomic Analyses Elucidate Adaptive Differences of Closely Related Strains of Pseudomonas aeruginosa in Fuel

Gunasekera

Bowen

Zhou

et al. 2017

Appl Environ Microbiol

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Pseudomonas aeruginosa can utilize hydrocarbons, but different strains have various degrees of adaptation despite their highly conserved genome. P. aeruginosa ATCC 33988 is highly adapted to hydrocarbons, while P. aeruginosa strain PAO1, a human pathogen, is less adapted and degrades jet fuel at a lower rate than does ATCC 33988. We investigated fuel-specific transcriptomic differences between these strains in order to ascertain the underlying mechanisms utilized by the adapted strain to proliferate in fuel. During growth in fuel, the genes related to alkane degradation, heat shock response, membrane proteins, efflux pumps, and several novel genes were upregulated in ATCC 33988. Overexpression of alk genes in PAO1 provided some improvement in growth, but it was not as robust as that of ATCC 33988, suggesting the role of other genes in adaptation. Expression of the function unknown gene PA5359 from ATCC 33988 in PAO1 increased the growth in fuel. Bioinformatic analysis revealed that PA5359 is a predicted lipoprotein with a conserved Yx(FWY)xxD motif, which is shared among bacterial adhesins. Overexpression of the putative resistance-nodulation-division (RND) efflux pump PA3521 to PA3523 increased the growth of the ATCC 33988 strain, suggesting a possible role in fuel tolerance. Interestingly, the PAO1 strain cannot utilize n-C 8 and n-C 10 . The expression of green fluorescent protein (GFP) under the control of alkB promoters confirmed that alk gene promoter polymorphism affects the expression of alk genes. Promoter fusion assays further confirmed that the regulation of alk genes was different in the two strains. Protein sequence analysis showed low amino acid differences for many of the upregulated genes, further supporting transcriptional control as the main mechanism for enhanced adaptation.IMPORTANCE These results support that specific signal transduction, gene regulation, and coordination of multiple biological responses are required to improve the survival, growth, and metabolism of fuel in adapted strains. This study provides new insight into the mechanistic differences between strains and helpful information that may be applied in the improvement of bacterial strains for resistance to biotic and abiotic factors encountered during bioremediation and industrial biotechnological processes.

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“…Interestingly, roughly one third of the genes making up the pangenome were present in only one of the more than 2,000 genomes employed in the study. A separate study employing 17 reference strains of Pseudomonas aeruginosa included 5,233 genes in the core genome [27]. These genes represented approximately 88% of the number of genes in the strains used in the study, and consisted of genes encoding enzymes involved in basic metabolic processes, virulence factors and antibiotic resistance determinants.…”

Section: Comparative Genomicsmentioning

confidence: 99%

Using bacterial genomes and essential genes for the development of new antibiotics

Fields

Lee

McConnell

2017

Biochemical Pharmacology

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The shrinking antibiotic development pipeline together with the global increase in antibiotic resistant infections requires that new molecules with antimicrobial activity are developed. Traditional empirical screening approaches of natural and non-natural compounds have identified the majority of antibiotics that are currently available, however this approach has produced relatively few new antibiotics over the last few decades. The vast amount of bacterial genome sequence information that has become available since the sequencing of the first bacterial genome more than 20 years ago holds potential for contributing to the discovery of novel antimicrobial compounds. Comparative genomic approaches can identify genes that are highly conserved within and between bacterial species, and thus may represent genes that participate in key bacterial processes. Whole genome mutagenesis studies can also identify genes necessary for bacterial growth and survival under different environmental conditions, making them attractive targets for the development of novel inhibitory compounds. In addition, transcriptomic and proteomic approaches can be used to characterize RNA and protein levels on a cellular scale, providing information on bacterial physiology that can be applied to antibiotic target identification. Finally, bacterial genomes can be mined to identify biosynthetic pathways that produce many intrinsic antimicrobial compounds and peptides. In this review, we provide an overview of past and current efforts aimed at using bacterial genomic data in the discovery and development of novel antibiotics.

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What It Takes to Be a Pseudomonas aeruginosa? The Core Genome of the Opportunistic Pathogen Updated

Cited by 99 publications

References 47 publications

Gene loss and acquisition in lineages of bacteria evolving in a human host environment

Gene loss and acquisition in lineages of bacteria evolving in a human host environment

Transcriptomic Analyses Elucidate Adaptive Differences of Closely Related Strains of Pseudomonas aeruginosa in Fuel

Using bacterial genomes and essential genes for the development of new antibiotics

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