Virulence factors in Pseudomonas aeruginosa: mechanisms and modes of regulation

Khalifa, A. Ben Haj; Moissenet, Didier; Thien, H. Vu; Khedher, Mohamed Raâfet Ben

doi:10.1684/abc.2011.0589

Cited by 75 publications

(67 citation statements)

References 112 publications

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“…It is a major nosocomial pathogen associated with significant morbidity and mortality (40–60%) in immunocompromised patients and in certain hospital units like burn and palliative care [29]. P. aeruginosa possesses several virulence factors, one of which is pyoverdine, the major siderophore that sequesters iron from the host to facilitate bacterial growth [30, 31]. Pyoverdine is a virulence factor required for establishing infection and biofilm formation [32].…”

Section: Discussionmentioning

confidence: 99%

Pyoverdine, the Major Siderophore inPseudomonas aeruginosa, Evades NGAL Recognition

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Bhatnagar

McCarty

et al. 2012

Interdisciplinary Perspectives on Infectious Diseases

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Pseudomonas aeruginosa is the most common pathogen that persists in the cystic fibrosis lungs. Bacteria such as P. aeruginosa secrete siderophores (iron-chelating molecules) and the host limits bacterial growth by producing neutrophil-gelatinase-associated lipocalin (NGAL) that specifically scavenges bacterial siderophores, therefore preventing bacteria from establishing infection. P. aeruginosa produces a major siderophore known as pyoverdine, found to be important for bacterial virulence and biofilm development. We report that pyoverdine did not bind to NGAL, as measured by tryptophan fluorescence quenching, while enterobactin bound to NGAL effectively causing a strong response. The experimental data indicate that pyoverdine evades NGAL recognition. We then employed a molecular modeling approach to simulate the binding of pyoverdine to human NGAL using NGAL's published crystal structures. The docking of pyoverdine to NGAL predicted nine different docking positions; however, neither apo- nor ferric forms of pyoverdine docked into the ligand-binding site in the calyx of NGAL where siderophores are known to bind. The molecular modeling results offer structural support that pyoverdine does not bind to NGAL, confirming the results obtained in the tryptophan quenching assay. The data suggest that pyoverdine is a stealth siderophore that evades NGAL recognition allowing P. aeruginosa to establish chronic infections in CF lungs.

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Section: Discussionmentioning

confidence: 99%

Pyoverdine, the Major Siderophore inPseudomonas aeruginosa, Evades NGAL Recognition

Peek

Bhatnagar

McCarty

et al. 2012

Interdisciplinary Perspectives on Infectious Diseases

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“…Pseudomonas aeruginosa is an opportunistic human pathogen that readily develops antibiotic resistance and it is a lethal pathogen of particular importance in cystic fibrosis patients (Stover et al, 2000). The bacterium produces a variety of virulence factors, such as Pseudomonas quinolone signal (PQS) (Mashburn & Whiteley, 2005), pyocyanin (Hassett et al, 1992), rhamnolipids (Zulianello et al, 2006), elastase (Pearson et al, 1997) and two endogenous siderophores, pyoverdine and pyochelin (Michel et al, 2005), which are involved in chronic infection (Ben Haj Khalifa et al, 2011). Pseudomonas aeruginosa also produces adhesion factors, exotoxin A, phospholipase C for hemolysis, and exoenzyme S, which are involved in acute infection (Ben Haj Khalifa et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…The bacterium produces a variety of virulence factors, such as Pseudomonas quinolone signal (PQS) (Mashburn & Whiteley, 2005), pyocyanin (Hassett et al, 1992), rhamnolipids (Zulianello et al, 2006), elastase (Pearson et al, 1997) and two endogenous siderophores, pyoverdine and pyochelin (Michel et al, 2005), which are involved in chronic infection (Ben Haj Khalifa et al, 2011). Pseudomonas aeruginosa also produces adhesion factors, exotoxin A, phospholipase C for hemolysis, and exoenzyme S, which are involved in acute infection (Ben Haj Khalifa et al, 2011). Furthermore, biofilm cells are up to 1000 times more resistant to antibiotics than planktonic cells are (Mah & O'Toole, 2001) and biofilm formation plays an important role in pathogenesis (Rasmussen & Givskov, 2006).…”

Section: Introductionmentioning

confidence: 99%

7-fluoroindole as an antivirulence compound against Pseudomonas aeruginosa

Lee

Kim

Cho

et al. 2012

FEMS Microbiol Lett

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The emergence of antibiotic resistance has necessitated new therapeutic approaches for combating persistent bacterial infection. An alternative approach is regulation of bacterial virulence instead of growth suppression, which can readily lead to drug resistance. The virulence of the opportunistic human pathogen Pseudomonas aeruginosa depends on a large number of extracellular factors and biofilm formation. Thirty-one natural and synthetic indole derivatives were screened. 7-fluoroindole (7FI) was identified as a compound that inhibits biofilm formation and blood hemolysis without inhibiting the growth of planktonic P. aeruginosa cells. Moreover, 7FI markedly reduced the production of quorum-sensing (QS)-regulated virulence factors 2-heptyl-3-hydroxy-4(1H)-quinolone, pyocyanin, rhamnolipid, two siderophores, pyoverdine and pyochelin. 7FI clearly suppressed swarming motility, protease activity and the production of a polymeric matrix in P. aeruginosa. However, unlike natural indole compounds, synthetic 7FI did not increase antibiotic resistance. Therefore, 7FI is a potential candidate for use in an antivirulence approach against persistent P. aeruginosa infection.

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“…AHL-mediated quorum sensing is involved in the regulation of multiple virulence determinants and the immune system is capable of responding to these bacterial signal molecules. Virulence is multifactorial and under the control of quorum-sensing signals, such as AHLs, these molecules either improve the virulence potential of P. aeruginosa or modulate the host immune response [21]. To establish the immunemodulating potential of quorum-sensing signal molecules, previous studies have only used synthetic AHLs.…”

Section: Host Immune Response In Acinetobacter Baumannii and Pseudomomentioning

confidence: 99%

Role of quorum-sensing molecules in infections caused by Gram-negative bacteria and host cell response

Gowda

Marie

2014

Reviews in Medical Microbiology

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Gram-negative bacteria communicate among themselves by cell-to-cell signaling molecules that are essential not only for interaction within the cell population, but also for host-pathogen interactions during infections. Pseudomonas aeruginosa and Acinetobacter baumannii are opportunistic Gram-negative pathogens associated with a broad range of acute and chronic infections, as well as causing severe nosocomial problems. The quorum-sensing signaling system controls not only multiple virulence determinants such as the assembly of virulence factors essential for colonizing and perseverance in different environmental conditions, but also interference with the host core signaling pathways. We discuss the quorum-sensing role in host response during infections, focusing on the collision of quorum-sensing molecules with the immune response and host cell apoptosis modulation pathways. The pathways used during the infectious course could open new perspectives for the expansion of specific antimicrobial strategies based on communication control of this extremely adaptable and resistant opportunistic pathogen.

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Virulence factors in Pseudomonas aeruginosa: mechanisms and modes of regulation

Cited by 75 publications

References 112 publications

Pyoverdine, the Major Siderophore inPseudomonas aeruginosa, Evades NGAL Recognition

Pyoverdine, the Major Siderophore inPseudomonas aeruginosa, Evades NGAL Recognition

7-fluoroindole as an antivirulence compound against Pseudomonas aeruginosa

Role of quorum-sensing molecules in infections caused by Gram-negative bacteria and host cell response

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