Extensive Genomic Plasticity in
            <i>Pseudomonas aeruginosa</i>
            Revealed by Identification and Distribution Studies of Novel Genes among Clinical Isolates

Shen, Kai; Sayeed, Sameera; Antalis, Patricia; Gladitz, John; Ahmed, Azad; Dice, Bethany; Janto, Benjamin; Dopico, Richard A.; Keefe, Randy; Hayes, J. D.; Johnson, Sharon L.; Yu, Shimeng; Ehrlich, Nathan E.; Jocz, Jennifer; Kropp, Laura E.; Wong, R. S C.; Wadowsky, Robert M.; Slifkin, Malcolm; Preston, Robert A.; Erdö́s, G.; Post, J. Christopher; Ehrlich, Garth D.; Hu, Fang

doi:10.1128/iai.00546-06

Cited by 76 publications

(73 citation statements)

References 59 publications

(60 reference statements)

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“…In many cases, this genetic variation results in altered expression of virulence factors or a loss altogether of genes encoding certain virulence determinants (51)(52)(53). To date, all sequenced isolates of P. aeruginosa possess the tandem arrangement of the prrF genes (71), indicating that the region encoding both the PrrF and PrrH sRNAs is part of the core genome of this species.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have demonstrated the plasticity of the P. aeruginosa genome, resulting in highly variable expression of virulence factors in differ- ent strains (51)(52)(53). We therefore determined the ability of several P. aeruginosa laboratory strains and clinical isolates to express and regulate the PrrF and PrrH sRNAs in response to iron and heme.…”

Section: Figmentioning

confidence: 99%

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The prrF -Encoded Small Regulatory RNAs Are Required for Iron Homeostasis and Virulence of Pseudomonas aeruginosa

et al. 2015

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Pseudomonas aeruginosa is an opportunistic pathogen that requires iron to cause infection, but it also must regulate the uptake of iron to avoid iron toxicity. The iron-responsive PrrF1 and PrrF2 small regulatory RNAs (sRNAs) are part of P. aeruginosa's iron regulatory network and affect the expression of at least 50 genes encoding iron-containing proteins. The genes encoding the PrrF1 and PrrF2 sRNAs are encoded in tandem in P. aeruginosa, allowing for the expression of a distinct, heme-responsive sRNA named PrrH that appears to regulate genes involved in heme metabolism. Using a combination of growth, mass spectrometry, and gene expression analysis, we showed that the ⌬prrF1,2 mutant, which lacks expression of the PrrF and PrrH sRNAs, is defective for both iron and heme homeostasis. We also identified phuS, encoding a heme binding protein involved in heme acquisition, and vreR, encoding a previously identified regulator of P. aeruginosa virulence genes, as novel targets of prrF-mediated heme regulation. Finally, we showed that the prrF locus encoding the PrrF and PrrH sRNAs is required for P. aeruginosa virulence in a murine model of acute lung infection. Moreover, we showed that inoculation with a ⌬prrF1,2 deletion mutant protects against future challenge with wild-type P. aeruginosa. Combined, these data demonstrate that the prrF-encoded sRNAs are critical regulators of P. aeruginosa virulence. Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium and versatile opportunistic pathogen. Iron is required for P. aeruginosa virulence (1-6) and is obtained through several mechanisms. In anaerobic environments, iron in its ferrous form is freely diffusible through the outer membrane (OM) and transported into the cytoplasm by the Feo inner membrane transport system (7,8). However, the insolubility of ferric iron in aerobic environments limits accessibility to this nutrient. Moreover, the sequestration of iron by host proteins creates a substantial barrier to infection (9, 10). To overcome this barrier, P. aeruginosa synthesizes and secretes two siderophores, pyoverdine and pyochelin, which scavenge ferric iron (1-4). P. aeruginosa can also acquire heme, an abundant source of iron in the human host (11). Once internalized, heme is sequestered by the cytosolic PhuS heme chaperone (12). PhuS transfers heme to the iron-regulated HemO heme oxygenase, which degrades heme to biliverdin, releasing carbon monoxide and iron (13,14). Several studies have shown that iron acquisition is essential for P. aeruginosa virulence (1-5) and biofilm formation (15-17), demonstrating the central role of this element in P. aeruginosa pathogenesis.Despite its essentiality, iron and heme can be toxic due to their ability to catalyze the formation of reactive oxygen species. Thus, to maintain iron homeostasis, P. aeruginosa must be able to not only acquire iron but also regulate uptake of iron and heme from the environment, as well as iron use and storage. Expression of genes encoding iron and heme uptake systems in P. aeruginosa is ...

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Section: Discussionmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

The prrF -Encoded Small Regulatory RNAs Are Required for Iron Homeostasis and Virulence of Pseudomonas aeruginosa

et al. 2015

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“…The effect of bacteriophages on populations is, as yet, unclear, but it has been shown that bacteriophages can drive diversification [64]. Extensive genome plasticity has been reported for P. aeruginosa clinical isolates, with phage sequences contributing to horizontal gene transfer and sequence diversity [65]. Furthermore, the presence of bacteriophages has been shown to present difficulties for some typing methods.…”

Section: Microbiological and Genomic Characteristics Of The Lesmentioning

confidence: 99%

Transmissible strains ofPseudomonas aeruginosain cystic fibrosis lung infections

Fothergill¹,

Walshaw²,

Winstanley³

2012

Eur Respir J

145

122

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Pseudomonas aeruginosa chronic lung infections are the major cause of morbidity and mortality associated with cystic fibrosis. For many years, the consensus was that cystic fibrosis patients acquire P. aeruginosa from the environment, and hence harbour their own individual clones. However, in the past 15 yrs the emergence of transmissible strains, in some cases associated with greater morbidity and increased antimicrobial resistance, has changed the way that many clinics treat their patients. Here we provide a summary of reported transmissible strains in the UK, other parts of Europe, Australia and North America. In particular, we discuss the prevalence, epidemiology, unusual genotypic and phenotypic features, and virulence of the most intensively studied transmissible strain, the Liverpool epidemic strain. We also discuss the clinical impact of transmissible strains, in particular the diagnostic and infection control approaches adopted to counter their spread. Genomic analysis carried out so far has provided little evidence that transmissibility is due to shared genetic characteristics between different strains. Previous experiences with transmissible strains should help us to learn lessons for the future. In particular, there is a clear need for strain surveillance if emerging problem strains are to be detected before they are widely transmitted.

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“…As shown for Haemophilus influenzae, P. aeruginosa, Streptococcus pneumoniae, and other bacterial pathogens, there is considerable variation in the DNA content of each isolate (18,29,41,42). The accessory genome of A. baumannii comprises 2,649 annotated genes that are present in one to five of the six isolates.…”

Section: Genomesmentioning

confidence: 99%

Comparative Genome Sequence Analysis of Multidrug-Resistant Acinetobacter baumannii

Adams¹,

Goglin²,

Molyneaux³

et al. 2008

J Bacteriol

415

420

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The recent emergence of multidrug resistance (MDR) in Acinetobacter baumannii has raised concern in health care settings worldwide. In order to understand the repertoire of resistance determinants and their organization and origins, we compared the genome sequences of three MDR and three drug-susceptible A. baumannii isolates. The entire MDR phenotype can be explained by the acquisition of discrete resistance determinants distributed throughout the genome. A comparison of closely related MDR and drug-susceptible isolates suggests that drug efflux may be a less significant contributor to resistance to certain classes of antibiotics than inactivation enzymes are. A resistance island with a variable composition of resistance determinants interspersed with transposons, integrons, and other mobile genetic elements is a significant but not universal contributor to the MDR phenotype. Four hundred seventy-five genes are shared among all six clinical isolates but absent from the related environmental species Acinetobacter baylyi ADP1. These genes are enriched for transcription factors and transporters and suggest physiological features of A. baumannii that are related to adaptation for growth in association with humans.Among gram-negative pathogens that are reported as "multidrug resistant" (MDR), Acinetobacter baumannii is rapidly becoming a focus of significant attention (1,10,35,56). A. baumannii, a pleomorphic, gram-negative coccobacillus, is currently recognized by the Infectious Diseases Society of America as one of the most important pathogens threatening our health care delivery system (48). Global surveillance programs conducted over the last decade show an unparalleled increase in resistance rates among clinical Acinetobacter isolates (26). Acinetobacter spp. are now the third leading cause of respiratory tract infections among patients in intensive care units, and A. baumannii is responsible for up to 10% of hospital-acquired infections (26). These nosocomial infections are typically found in immunocompromised patients and are associated with an increased length of stay and excess morbidity (13,25,38,47 (19,40). Molecular typing of isolates from this outbreak revealed eight major clone types, and about 60% of the isolates were related to three pan-European types (5, 52), suggesting multiple independent origins (40). Examination of specific resistance determinants in the WRAMC isolates demonstrated considerable variability in the composition of resistance genes within each clone type and similar patterns across certain divergent clone types. Thus, genetic relatedness was a poor predictor of the MDR phenotype. This led to the hypothesis that there exist multiple independent genetic mechanisms leading to MDR in A. baumannii. A large cluster of antibiotic resistance genes and mobile genetic elements is present as an 86-kb "resistance island" (RI) in the A. baumannii AYE genome (15). The RI is not present in the genomes of the drug-susceptible A. baumannii isolates ATCC 17978 (43) and SDF (51), suggesting that it i...

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Extensive Genomic Plasticity in Pseudomonas aeruginosa Revealed by Identification and Distribution Studies of Novel Genes among Clinical Isolates

Cited by 76 publications

References 59 publications

The prrF -Encoded Small Regulatory RNAs Are Required for Iron Homeostasis and Virulence of Pseudomonas aeruginosa

The prrF -Encoded Small Regulatory RNAs Are Required for Iron Homeostasis and Virulence of Pseudomonas aeruginosa

Transmissible strains ofPseudomonas aeruginosain cystic fibrosis lung infections

Comparative Genome Sequence Analysis of Multidrug-Resistant Acinetobacter baumannii

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