Pseudomonas aeruginosa Cytotoxins: Mechanisms of Cytotoxicity and Impact on Inflammatory Responses

Wood, Stephen; Goldufsky, Josef W.; Seu, Michelle; Dorafshar, Amir H.; Shafikhani, Sasha H.

doi:10.3390/cells12010195

Cited by 23 publications

(24 citation statements)

References 361 publications

(563 reference statements)

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“…After infection, keratinocytes release many immune markers to eliminate bacteria (33). Our results are consistent with the theory reported previously, which pyocyanin production by P. aeruginosa can cause the release of TNF-α which induced the expression of IL-8, IL-1 and IL-6 in the infected host cells (34,35). Besides, the release of inflammatory markers helps in balancing combating the infection and minimizing host cells or tissue damage.…”

Section: Discussionsupporting

confidence: 93%

Unveiling the Anti-Adhesive Potential of Tetraspanin CD9 Peptides againstPseudomonas aeruginosain Human Keratinocytes

Murad,

Ab-Rahim,

Al-Talib

2023

Preprint

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Multidrug-resistant P. aeruginosa strains are becoming a public health problem worldwide, causing numerous nosocomial infections. Adhesion of bacteria to host cells is a crucial step in infection, hence interruption of this stage can reduce bacterial infection. Tetraspanin CD9 was chosen for this study as it has been implicated in the pathogenesis of bacterial infections in a previous study. The aim of this study is to investigate the adhesion inhibition of tetraspanin CD9 peptides against P. aeruginosa in human keratinocytes. HaCaT cells were infected with P. aeruginosa, prior to treatment with CD9 peptides. The CD9 peptides cytotoxicity testing was determined by MTT assay. Bacterial adhesion was also determined quantitatively by counting viable bacterial cells and qualitatively by Giemsa staining and transmission electron microscope. Inflammatory markers (IL-8 and IL-6) expression was measured by Elisa assay. CD9 peptides did not affect HaCaT cell viability and inflammatory markers release. This study successfully demonstrated that CD9 peptides reduced P. aeruginosa adherence. Colonies produced by P. aeruginosa isolates treated with CD9 peptides were significantly reduced. Giemsa staining and TEM showed that treated samples had lower bacterial density and were located farther from the cells. These data suggest that tetraspanin CD9 peptides as the potential therapeutic approach against P. aeruginosa due to its property that inhibits bacterial adhesion without killing the bacteria, whereby at the same time does not adversely affect the nature of host cells.

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Section: Discussionsupporting

confidence: 93%

Unveiling the Anti-Adhesive Potential of Tetraspanin CD9 Peptides againstPseudomonas aeruginosain Human Keratinocytes

Murad,

Ab-Rahim,

Al-Talib

2023

Preprint

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“…However, a strong decrease in TEER was observed when both P. aeruginosa strains were added to Calu-3 cells alone, or co-inoculated with A. fumigatus. P. aeruginosa has a strong cytotoxicity effect [39], and is known to have a disruptive effect on TEER [40]. Permeability assay using the paracellular marker LY showed similar results.…”

Section: Discussionmentioning

confidence: 67%

“…These observations were confirmed by the cytotoxicity assay, which showed a high fluorescent signal in the presence of P. aeruginosa b2 alone, or co-inoculated with A. fumigatus, suggesting the release of high numbers of dead-cell proteases. P. aeruginosa is known to have a strong cytotoxicity effect in lung epithelial cells, notably through the induction of various forms of cell death, leading to cell lysis [39]. Epithelial barrier integrity was assessed through TEER measurements over 16 days, as well as LY permeability assay as an end-point measurement.…”

Section: Discussionmentioning

confidence: 99%

One-Step Soft Agar Enrichment and Isolation of Human Lung Bacteria Inhibiting the Germination of Aspergillus fumigatus conidia

Palmieri,

Magnin,

Diserens

et al. 2023

Preprint

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Fungi of the genus Aspergillus are widespread in the environment where they produce large quantities of airborne conidia. Inhalation of Aspergillus spp. conidia in immunocompromised individuals can cause a wide spectrum of diseases, ranging from hypersensitivity responses to lethal invasive infections. Upon deposition in the lung epithelial surface, conidia encounter and interact with complex microbial communities that constitute the lung microbiota. The lung microbiota has been suggested to influence the establishment and growth of Aspergillus spp. in the human airways. However, the mechanisms underlying this interaction have not yet been sufficiently investigated. In this study, we aimed to evaluate the presence of commensal bacteria antagonistic to Aspergillus in the lung. To this end, we enriched and isolated bacterial strains able to inhibit the germination of conidia from bronchoalveolar lavage fluid (BALF) samples of lung transplant recipients. We used a novel enrichment method based on a soft agar overlay plate assay in which bacteria are directly in contact with conidia and for which inhibition can be readily observed during enrichment. We isolated a total of five bacterial strains, identified as Pseudomonas aeruginosa, and able to inhibit the germination and growth of Aspergillus fumigatus in a soft agar confrontation assay, as well as in a high-throughput multiplate assay. Moreover, we also showed a strong inhibition of A. fumigatus growth on Calu-3 cell culture monolayers. However, the isolated P. aeruginosa strains were shown to cause significant damage to the cell monolayers. Overall, we validated this novel one-step enrichment approach for the isolation of bacterial strains antagonistic to A. fumigatus from BALF samples. This opens up a new venue for targeted enrichment of antagonistic bacterial strains against specific fungal pathogens.

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“…A major pathogenicity strategy of P. aeruginosa is the production of enzymes and toxins that induce cytotoxicity and various forms of cell death in target host cells [67]. ExoU (for extotoxin U) is a potent cytotoxic A2 phospholipase capable of causing rapid cell death in eukaryotic cells by producing a loss in plasma membrane integrity and necrosis [68] (Table 1).…”

Section: Extracellular Invasive Enzymes and Toxinsmentioning

confidence: 99%

Transcriptional Regulators Controlling Virulence in Pseudomonas aeruginosa

Sánchez-Jiménez

Llamas

Marcos‐Torres

2023

IJMS

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Pseudomonas aeruginosa is a pathogen capable of colonizing virtually every human tissue. The host colonization competence and versatility of this pathogen are powered by a wide array of virulence factors necessary in different steps of the infection process. This includes factors involved in bacterial motility and attachment, biofilm formation, the production and secretion of extracellular invasive enzymes and exotoxins, the production of toxic secondary metabolites, and the acquisition of iron. Expression of these virulence factors during infection is tightly regulated, which allows their production only when they are needed. This process optimizes host colonization and virulence. In this work, we review the intricate network of transcriptional regulators that control the expression of virulence factors in P. aeruginosa, including one- and two-component systems and σ factors. Because inhibition of virulence holds promise as a target for new antimicrobials, blocking the regulators that trigger the production of virulence determinants in P. aeruginosa is a promising strategy to fight this clinically relevant pathogen.

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Pseudomonas aeruginosa Cytotoxins: Mechanisms of Cytotoxicity and Impact on Inflammatory Responses

Cited by 23 publications

References 361 publications

Unveiling the Anti-Adhesive Potential of Tetraspanin CD9 Peptides againstPseudomonas aeruginosain Human Keratinocytes

Unveiling the Anti-Adhesive Potential of Tetraspanin CD9 Peptides againstPseudomonas aeruginosain Human Keratinocytes

One-Step Soft Agar Enrichment and Isolation of Human Lung Bacteria Inhibiting the Germination of Aspergillus fumigatus conidia

Transcriptional Regulators Controlling Virulence in Pseudomonas aeruginosa

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