Role of the Quorum-sensing System in Experimental Pneumonia due to <i>Pseudomonas aeruginosa</i> in Rats

Lesprit, Philippe; Faurisson, François; Join‐Lambert, Olivier; Roudot‐Thoraval, Françoise; Foglino, Maryline; Vissuzaine, C; Carbon, C

doi:10.1164/rccm.200207-736bc

Cited by 72 publications

(51 citation statements)

References 18 publications

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“…The fact that a lasR mutant exhibits significantly reduced virulence in a mouse model of pneumonia demonstrates the importance of quorum sensing in the pathogenesis of P. aeruginosa infection (18,38). Consistent with this, our results indicated that the PmlI-PmlR quorum-sensing system is essential for the pathogenesis of melioidosis, as a pmlI mutant of B. pseudomallei is less virulent than the wild-type strain in a murine model of infection when either the intraperitoneal, subcutaneous, or intranasal route is used.…”

Section: Discussionmentioning

confidence: 99%

The PmlI-PmlR Quorum-Sensing System in Burkholderia pseudomallei Plays a Key Role in Virulence and Modulates Production of the MprA Protease

et al. 2004

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Burkholderia pseudomallei is the causative agent of melioidosis, an often fatal infection of humans and animals. The virulence of this pathogen is thought to depend on a number of secreted proteins, including the MprA metalloprotease. We observed that MprA is produced upon entry into the stationary phase, when the cell density is high, and this prompted us to study cell density-dependent regulation in B. pseudomallei. A search of the B. pseudomallei genome led to identification of a quorum-sensing system involving the LuxI-LuxR homologs PmlI-PmlR. PmlI directed the synthesis of an N-acylhomoserine lactone identified as N-decanoylhomoserine lactone. A B. pseudomallei pmlI mutant was significantly less virulent than the parental strain in a murine model of infection by the intraperitoneal, subcutaneous, and intranasal routes. Inactivation of pmlI resulted in overproduction of MprA at the onset of the stationary phase. A wild-type phenotype was restored following complementation with pmlI or addition of cell-free culture supernatant. In contrast, there was no significant difference between the virulence of a B. pseudomallei mprA mutant and the virulence of the wild-type strain. These results suggest that the PmlI-PmlR quorum-sensing system of B. pseudomallei is essential for full virulence in a mouse model and downregulates the production of MprA at a high cell density.

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Section: Discussionmentioning

confidence: 99%

The PmlI-PmlR Quorum-Sensing System in Burkholderia pseudomallei Plays a Key Role in Virulence and Modulates Production of the MprA Protease

et al. 2004

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“…However, almost all of these measurements have been carried out with a limited number of mostly laboratory strains, with little data available for clinical isolates from different infections (16,22,29). Although animal studies in models of burn wound infection and pneumonia (13,21,27,31) indicate a role for QS-regulated genes in pathogenesis, these studies were also carried out by using single laboratory strains. Here, we analyzed the relationship between transcription of one of the key QS regulators, lasR, and two important virulence factors whose transcription is controlled by LasR, lasB, and aprA.…”

Section: Discussionmentioning

confidence: 99%

Transcription of Quorum-Sensing System Genes inClinical and Environmental Isolates of Pseudomonasaeruginosa

et al. 2003

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Quorum sensing (QS)-based transcriptional responses inPseudomonas aeruginosa have been defined on the basis of increases in transcript levels of QS-controlled genes such as lasB and aprA following the hierarchical transcriptional increases of central controllers such as the lasR gene. These increases occur at high bacterial concentrations such as early-stationary-phase growth in vitro. However, the extent to which the increases occur in a variety of clinical and environmental isolates has not been determined nor is there extensive information on allelic variation in lasR genes. An analysis of the sequences of the lasR gene among 66 clinical and environmental isolates showed that 81% have a sequence either identical to that of strain PAO1 or with a silent mutation, 15% have nucleotide changes resulting in amino acid changes, and 5% have an insertion sequence in the lasR gene. Using real-time PCR to quantify transcript levels of lasR, lasB, and aprA in the early log and early stationary phases among 35 isolates from bacteremia and pneumonia cases and the environment, we found most (33 of 35) strains had increases in lasR transcripts in early stationary phase but with a very wide range of final transcript levels per cell. There was a strong correlation (r 2 ‫؍‬ 0.84) between early-log-and early-stationary-phase transcript levels in all strains, but this finding remained true only for the 50% of strains above the median level of lasR found in early log phase. There were significant (P < 0.05) but weak-to-modest correlations of lasR transcript levels with aprA (r 2 ‫؍‬ 0.2) and lasB (r 2 ‫؍‬ 0.5) transcript levels, but again this correlation occurred only in the 50% of P. aeruginosa strains with the highest levels of lasR transcripts in early stationary phase. There were no differences in distribution of lasR alleles among the bacteremia, pneumonia, or environmental isolates. Overall, only about 50% of P. aeruginosa strains from clinical and environmental sources show a lasR-dependent increase in the transcription of aprA and lasB genes, indicating that for about 50% of clinical isolates this regulatory system may not play a significant role in pathogenesis.Pseudomonas aeruginosa is a ubiquitous environmental organism able to colonize and infect humans with underlying genetic susceptibilities (14) or under opportunistic conditions. Ventilated patients hospitalized in intensive care units are often highly susceptible to P. aeruginosa colonization in the upper respiratory tract (throat and/or trachea) (1, 8). The transition from colonization to infection by P. aeruginosa is often seen in the setting of immunosuppression of host defenses such as occurs in cancer patients undergoing chemotherapy, when the blood levels of polymorphonuclear neutrophils are below 100/mm 3 (26). In addition, controlled transcription and synthesis of genes and proteins involved in virulence are thought to be instrumental in sensing the host environment and producing appropriate bacterial responses.The transcription of genes encoding several v...

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“…These quorumsensing gene products are responsible for regulating production of several virulence factors, including lectins (190,222); aminopeptidase, endoproteinase, and lipase (158); and rhamnolipid (166,232). Several studies have shown quorum-sensing mutants to be avirulent or less virulent than the wild-type strain in mouse (167,185,195,232), amoeba (34), and rat models (126). Finally, the role of S in P. aeruginosa virulence is highly dependent on the model system in which it is assessed.…”

Section: Sigma S (Rpos)mentioning

confidence: 99%

Alternative Sigma Factors and Their Roles in Bacterial Virulence

Kazmierczak

Wiedmann

Boor

2005

Microbiol Mol Biol Rev

311

305

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SUMMARY Sigma factors provide promoter recognition specificity to RNA polymerase holoenzyme, contribute to DNA strand separation, and then dissociate from the core enzyme following transcription initiation. As the regulon of a single sigma factor can be composed of hundreds of genes, sigma factors can provide effective mechanisms for simultaneously regulating expression of large numbers of prokaryotic genes. One newly emerging field is identification of the specific roles of alternative sigma factors in regulating expression of virulence genes and virulence-associated genes in bacterial pathogens. Virulence genes encode proteins whose functions are essential for the bacterium to effectively establish an infection in a host organism. In contrast, virulence-associated genes can contribute to bacterial survival in the environment and therefore may enhance the capacity of the bacterium to spread to new individuals or to survive passage through a host organism. As alternative sigma factors have been shown to regulate expression of both virulence and virulence-associated genes, these proteins can contribute both directly and indirectly to bacterial virulence. Sigma factors are classified into two structurally unrelated families, the σ70 and the σ54 families. The σ70 family includes primary sigma factors (e.g., Bacillus subtilis σA) as well as related alternative sigma factors; σ54 forms a distinct subfamily of sigma factors referred to as σN in almost all species for which these proteins have been characterized to date. We present several examples of alternative sigma factors that have been shown to contribute to virulence in at least one organism. For each sigma factor, when applicable, examples are drawn from multiple species.

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Role of the Quorum-sensing System in Experimental Pneumonia due to Pseudomonas aeruginosa in Rats

Cited by 72 publications

References 18 publications

The PmlI-PmlR Quorum-Sensing System in Burkholderia pseudomallei Plays a Key Role in Virulence and Modulates Production of the MprA Protease

The PmlI-PmlR Quorum-Sensing System in Burkholderia pseudomallei Plays a Key Role in Virulence and Modulates Production of the MprA Protease

Transcription of Quorum-Sensing System Genes inClinical and Environmental Isolates of Pseudomonasaeruginosa

Alternative Sigma Factors and Their Roles in Bacterial Virulence

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