Conservation of genome content and virulence determinants among clinical and environmental isolates of
            <i>Pseudomonas aeruginosa</i>

374

377

The ubiquitous bacterium Pseudomonas aeruginosa is the quintessential opportunistic pathogen. Certain isolates infect a broad range of host organisms, from plants to humans. The pathogenic promiscuity of particular variants may reflect an increased virulence gene repertoire beyond the core P. aeruginosa genome. We have identified and characterized two P. aeruginosa pathogenicity islands (PAPI-1 and PAPI-2) in the genome of PA14, a highly virulent clinical isolate. The 108-kb PAPI-1 and 11-kb PAPI-2, which are absent from the less virulent reference strain PAO1, exhibit highly modular structures, revealing their complex derivations from a wide array of bacterial species and mobile elements. Most of the genes within these islands that are homologous to known genes occur in other human and plant bacterial pathogens. For example, PAPI-1 carries a complete gene cluster predicted to encode a type IV group B pilus, a well known adhesin absent from strain PAO1. However, >80% of the PAPI-1 DNA sequence is unique, and 75 of its 115 predicted ORF products are unrelated to any known proteins or functional domains. Significantly, many PAPI-1 ORFs also occur in several P. aeruginosa cystic fibrosis isolates. Twenty-three PAPI ORFs were mutated, and 19 were found to be necessary for full plant or animal virulence, with 11 required for both. The large set of ''extra'' virulence functions encoded by both PAPIs may contribute to the increased promiscuity of highly virulent P. aeruginosa strains, by directing additional pathogenic functions.

“…All P. aeruginosa strains are human isolates (6,15,16). The TnphoA mutant 33A9 has been described (21).…”

Section: Methodsmentioning

confidence: 99%

Section: Papi-1 Is a Pathogenicity Islandmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

The broad host range pathogen Pseudomonas aeruginosa strain PA14 carries two pathogenicity islands harboring plant and animal virulence genes

Baldini

Déziel

et al. 2004

374

377

“…Although most P. aeruginosa strains in the environment rarely encounter a suitable human host, they possess a set of highly conserved genes encoding virulence determinants whose products have specific host targets (8). The pathogenesis of P. aeruginosa lung infections in CF likely requires the coordinately regulated expression of distinct sets of virulence determinants at different disease stages.…”

mentioning

confidence: 99%

Pseudomonas aeruginosaregulates flagellin expression as part of a global response to airway fluid from cystic fibrosis patients

Wolfgang

Jyot

Goodman

et al. 2004

Self Cite

139

137

Cystic fibrosis (CF) patients are highly susceptible to chronic lung infections by the environmental bacterium Pseudomonas aeruginosa. The overproduction and accumulation of dehydrated viscous respiratory mucus and excessive inflammation represents a defining feature of CF and constitutes the major environment encountered by P. aeruginosa during chronic infections. We applied whole-genome microarray technology to investigate the ability of P. aeruginosa to respond to signals found in muco-purulent airway liquids collected from chronically infected CF patients. Particularly notable was the activation of the Rhl-dependent quorum-sensing (QS) network and repression of fliC, which encodes flagellin. Activation of the Rhl branch of the QS network supports the observation that QS molecules are produced in the chronically infected CF lung. The shut-off of flagellin synthesis in response to CF airway liquids was rapid and independent of QS and the known regulatory networks controlling the hierarchical expression of flagellar genes. As flagellin is highly immunogenic and subject to detection by host pattern recognition receptors, its repression may represent an adaptive response that allows P. aeruginosa to avoid detection by host defense mechanisms and phagocytosis during the chronic phase of CF lung infections.

“…In other species, such as Mycobacterium tuberculosis, the comparison of complete genome sequences has identified large-sequence polymorphisms (LSPs) and singlenucleotide polymorphisms (SNPs), but the molecular basis of variability in virulence and transmissibility remains undefined (6,7). A distinct but complementary approach to comparative genomics involves the interrogation of unsequenced genomes by DNA microarray to identify sequences present in a fully sequenced isolate, but absent from interrogated isolates (8)(9)(10)(11)(12)(13)(14)(15)(16). Although this approach is limited to the identification of relatively large sequence polymorphisms, it allows for the comparison of a large number of genomes, and thus provides information on the diversity and frequency of polymorphisms in the population.…”

mentioning

confidence: 99%

Functional and evolutionary genomics of Mycobacterium tuberculosis : Insights from genomic deletions in 100 strains

Tsolaki

Hirsh

DeRiemer

et al. 2004

332

305

To better understand genome function and evolution in Mycobacterium tuberculosis, the genomes of 100 epidemiologically well characterized clinical isolates were interrogated by DNA microarrays and sequencing. We identified 68 different large-sequence polymorphisms (comprising 186,137 bp, or 4.2% of the genome) that are present in H37Rv, but absent from one or more clinical isolates. A total of 224 genes (5.5%), including genes in all major functional categories, were found to be partially or completely deleted. Deletions are not distributed randomly throughout the genome but instead tend to be aggregated. The distinct deletions in some aggregations appear in closely related isolates, suggesting a genomically disruptive process specific to an individual mycobacterial lineage. Other genomic aggregations include distinct deletions that appear in phylogenetically unrelated isolates, suggesting that a genomic region is vulnerable throughout the species. Although the deletions identified here are evidently inessential to the causation of disease (they are found in active clinical cases), their frequency spectrum suggests that most are weakly deleterious to the pathogen. For some deletions, short-term evolutionary pressure due to the host immune system or antibiotics may favor the elimination of genes, whereas longer-term physiological requirements maintain the genes in the population.