Impairment of Apoptotic Cell Engulfment by Pyocyanin, a Toxic Metabolite of<i>Pseudomonas aeruginosa</i>

Bianchi, Stephen; Prince, Lynne R.; McPhillips, Kathleen A.; Allen, Lucy; Marriott, Helen M.; Taylor, Graham W.; Hellewell, Paul G.; Sabroe, Ian; Dockrell, David H.; Henson, P.W.; Whyte, Moira K. B.

doi:10.1164/rccm.200612-1804oc

Cited by 96 publications

(67 citation statements)

References 53 publications

(77 reference statements)

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“…1b to d, DMSO significantly repressed the expression of phzA1 and phzA2, which probably explains the reduced level of phenazine production with the presence of DMSO in the medium. Since phenazine compounds, including pyocyanin, are products controlled by the QS system in P. aeruginosa (46,47), we tested whether the expression of genes associated with the QS system were influenced by DMSO. The results (Table 2) indicate that the expression of QS-related genes, including lasI, lasR, rhlI, rhlR, lasB, and rhlA, was inhibited by DMSO.…”

Section: Resultsmentioning

confidence: 99%

Potential Use of Dimethyl Sulfoxide in Treatment of Infections Caused by Pseudomonas aeruginosa

Qiao

Bai

et al. 2016

Antimicrob Agents Chemother

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c Dimethyl sulfoxide (DMSO) is commonly used as a solvent to dissolve water-insoluble drugs or other test samples in both in vivo and in vitro experiments. It was observed during our experiment that DMSO at noninhibitory concentrations could significantly inhibit pyocyanin production in the human pathogen Pseudomonas aeruginosa. Pyocyanin is an important pathogenic factor whose production is controlled by a cell density-dependent quorum-sensing (QS) system. Investigation of the effect of DMSO on QS showed that DMSO has significant QS antagonistic activities and concentrations of DMSO in the micromolar range attenuated a battery of QS-controlled virulence factors, including rhamnolipid, elastase, and LasA protease production and biofilm formation. Further study indicated that DMSO inhibition of biofilm formation and pyocyanin production was attained by reducing the level of production of an autoinducer molecule of the rhl QS system, N-butanoyl-L-homoserine lactone (C 4 -HSL). In a mouse model of a burn wound infection with P. aeruginosa, treatment with DMSO significantly decreased mouse mortality compared with that for mice in the control group. The capacity of DMSO to attenuate the pathogenicity of P. aeruginosa points to the potential use of DMSO as an antipathogenic agent for the treatment of P. aeruginosa infection. As a commonly used solvent, however, DMSO's impact on bacterial virulence calls for cautionary attention in its usage in biological, medicinal, and clinical studies. Pseudomonas aeruginosa is a prevalent opportunistic pathogen capable of causing various infections in humans, including pneumonia and urinary tract infections, bloodstream infections, and infections in burn patients (1). The chronic infection caused by P. aeruginosa and the associated pulmonary inflammation are ultimately responsible for the majority of cases of mortality in patients with cystic fibrosis (2). The ability of P. aeruginosa to cause diverse infections is attributed to its myriad virulence factors and biofilm-forming capability, which are controlled by the intercellular quorum-sensing (QS) communication system (3-5).P. aeruginosa has two acyl-homoserine lactone (AHL)-mediated QS systems, known as the las and rhl QS systems. The las and rhl systems consist of the transcriptional activators LasR and RhlR, respectively, and the signal synthases LasI and RhlI, respectively. The major signals in the las and rhl systems are N-(3-oxododecanoyl)-HSL (3-oxo-C 12 -HSL) and N-butanoyl-L-homoserine lactone (C 4 -HSL), respectively (5). P. aeruginosa employs these QS systems to control a wide range of extracellular virulence factors, including pyocyanin, elastase, and rhamnolipid (7-12). The AHL-mediated QS systems also play a crucial role in biofilm formation by P. aeruginosa, a common cause of resistance to antibiotics and the difficulties with the treatment of infections (13). The las system influences the activation of pel and, accordingly, biofilm matrix formation (14), and the rhl system contributes to the maintenance of the bio...

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Section: Resultsmentioning

confidence: 99%

Potential Use of Dimethyl Sulfoxide in Treatment of Infections Caused by Pseudomonas aeruginosa

Qiao

Bai

et al. 2016

Antimicrob Agents Chemother

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“…Ultimately, ineffective efferocytosis and accumulation of apoptotic cells in CF (2,48,53) may present fertile ground for novel therapies, especially if efferocytosis is defective in macrophages (53) and epithelial cells. Drugs that specifically block the RhoA/Rho kinase pathway may, if applied early, control the apoptotic cell burden and maintain lung homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Dysfunctional cystic fibrosis transmembrane conductance regulator inhibits phagocytosis of apoptotic cells with proinflammatory consequences

Vandivier

Richens

Horstmann

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…A model of apoptosis cells was established based on exposure of mouse thymocytes to ultraviolet radiation in vitro to explore the role of Siglec-F in macrophage phagocytosis (Vandivier et al, 2002;Morimoto et al, 2006;Bianchi et al, 2008). Thymuses obtained from mice (aged 3-4 weeks) were gently pushed through a cell strainer (40 μm) to prepare a thymocyte suspension.…”

Section: Isolation Of Thymocytes and Apoptosis Inductionmentioning

confidence: 99%

Expression and preliminary functional analysis of Siglec-F on mouse macrophages

Feng

Mao

2012

J. Zhejiang Univ. Sci. B

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Impairment of Apoptotic Cell Engulfment by Pyocyanin, a Toxic Metabolite ofPseudomonas aeruginosa

Abstract: These studies demonstrate that P. aeruginosa can manipulate the inflammatory microenvironment through inhibition of apoptotic cell engulfment, and suggest potential strategies to limit pulmonary inflammation in cystic fibrosis.

Cited by 96 publications

References 53 publications

Potential Use of Dimethyl Sulfoxide in Treatment of Infections Caused by Pseudomonas aeruginosa

Potential Use of Dimethyl Sulfoxide in Treatment of Infections Caused by Pseudomonas aeruginosa

Dysfunctional cystic fibrosis transmembrane conductance regulator inhibits phagocytosis of apoptotic cells with proinflammatory consequences

Expression and preliminary functional analysis of Siglec-F on mouse macrophages

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