Surfactant Protein D Influences Mortality During Abdominal Sepsis by Facilitating Escherichia coli Colonization in the Gut

Varon, Jack; Rubio, Antonio Arciniegas; Amador-Munoz, Diana; Corcoran, A. C.; DeCorte, Joseph A.; Isabelle, Colleen; Vera, Miguel Pinilla; Walker, Kathleen; Brown, Luke A.; Cernadas, Manuela; Bry, Lynn; Yang, Haopu; Kitsios, Georgios D; McVerry, Bryan J.; Morris, Alison; Lee, Hyunwook; Howrylak, Judie A.; Englert, Joshua A.; Baron, Rebecca M.

doi:10.1097/cce.0000000000000699

Cited by 4 publications

(2 citation statements)

References 41 publications

(48 reference statements)

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“…Also, surfactant protein (PDB ID: 1PW9) is antimicrobial in nature and potentially inhibits cell proliferation of gram-negative bacteria by the action of improving cell membrane permeability [ 15 ]. Another study reported that the enteral surfactant protein D worsens mortality after CLP by enhancing bacterial colonization in the gut [ 28 ]. Lactobacillus bacterial protein (PDB ID: 4MKS) was found to be the primary cause of septic urinary infection [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Docking of Bacterial Protein Modulators and Pharmacotherapeutics of Carica papaya Leaves as a Promising Therapy for Sepsis: Synchronising In Silico and In Vitro Studies

et al. 2023

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Sepsis is a serious health concern globally, which necessitates understanding the root cause of infection for the prevention of proliferation inside the host’s body. Phytochemicals present in plants exhibit antibacterial and anti-proliferative properties stipulated for sepsis treatment. The aim of the study was to determine the potential role of Carica papaya leaf extract for sepsis treatment in silico and in vitro. We selected two phytochemical compounds, carpaine and quercetin, and docked them with bacterial proteins, heat shock protein (PDB ID: 4PO2), surfactant protein D (PDB ID: 1PW9), and lactobacillus bacterial protein (PDB ID: 4MKS) against imipenem and cyclophosphamide. Quercetin showed the strongest interaction with 1PW9 and 4MKS proteins. The leaves were extracted using ethanol, methanol, and water through Soxhlet extraction. Total flavonoid content, DPPH assay, HPTLC, and FTIR were performed. In vitro cytotoxicity of ethanol extract was screened via MTT assay on the J774 cell line. Ethanol extract (EE) possessed the maximum number of phytocomponents, the highest amount of flavonoid content, and the maximum antioxidant activity compared to other extracts. FTIR analysis confirmed the presence of N-H, O-H, C-H, C=O, C=C, and C-Cl functional groups in ethanol extract. Cell viability was highest (100%) at 25 µg/mL of EE. The present study demonstrated that the papaya leaves possessed antibacterial and cytotoxic activity against sepsis infection.

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Section: Discussionmentioning

confidence: 99%

Molecular Docking of Bacterial Protein Modulators and Pharmacotherapeutics of Carica papaya Leaves as a Promising Therapy for Sepsis: Synchronising In Silico and In Vitro Studies

et al. 2023

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“…Cecal Ligation and Puncture (CLP). CLP was performed as previously described 99 . Briefly, after induction of anesthesia and analgesia with ketamine (85 mg/kg) and xylazine (34 mg/kg), mice were anesthetized, and a midline laparotomy was performed.…”

Section: Models Of Infectionmentioning

confidence: 99%

Identification and targeting of microbial putrescine acetylation in bloodstream infections

Mayers,

Varon,

Zhou

et al. 2023

Preprint

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The growth of antimicrobial resistance (AMR) has highlighted an urgent need to identify bacterial pathogenic functions that may be targets for clinical intervention. Although severe bacterial infections profoundly alter host metabolism, prior studies have largely ignored alterations in microbial metabolism in this context. Performing metabolomics on patient and mouse plasma samples, we identify elevated levels of bacterially-derived N-acetylputrescine during gram-negative bloodstream infections (BSI), with higher levels associated with worse clinical outcomes. We discover that SpeG is the bacterial enzyme responsible for acetylating putrescine and show that blocking its activity reduces bacterial proliferation and slows pathogenesis. Reduction of SpeG activity enhances bacterial membrane permeability and results in increased intracellular accumulation of antibiotics, allowing us to overcome AMR of clinical isolates both in culture and in vivo. This study highlights how studying pathogen metabolism in the natural context of infection can reveal new therapeutic strategies for addressing challenging infections.

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A metabolomics pipeline highlights microbial metabolism in bloodstream infections

Mayers,

Varon,

Zhou

et al. 2024

Cell

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Surfactant Protein D Influences Mortality During Abdominal Sepsis by Facilitating Escherichia coli Colonization in the Gut

Cited by 4 publications

References 41 publications

Molecular Docking of Bacterial Protein Modulators and Pharmacotherapeutics of Carica papaya Leaves as a Promising Therapy for Sepsis: Synchronising In Silico and In Vitro Studies

Molecular Docking of Bacterial Protein Modulators and Pharmacotherapeutics of Carica papaya Leaves as a Promising Therapy for Sepsis: Synchronising In Silico and In Vitro Studies

Identification and targeting of microbial putrescine acetylation in bloodstream infections

A metabolomics pipeline highlights microbial metabolism in bloodstream infections

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