cydA, spdC, and mroQ are novel genes involved in the plasma coagulation of Staphylococcus aureus

Luo, Dong; Wang, Wei; Chen, Qiang; Peng, Linfeng; Hu, Xiaomei; Chen, Kaisen

doi:10.1111/1348-0421.12922

Cited by 5 publications

(3 citation statements)

References 27 publications

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“…Adding to the uncertainty, a recent study has even suggested that MroQ might hydrolyze the AIP, leading to the downstream inactivation of AgrC and by extension agr QS. 38 Our biochemical studies clarify this picture by firmly establishing a direct role for MroQ in the second step of AIP biosynthesis, at least for agr groups I and II. Moreover, we see no evidence that the enzyme metabolizes the mature AIP.…”

Section: In a Key Pair Of Studies Cosgriff Et Al And Marroquin Et Al ...mentioning

confidence: 58%

“…However, these investigators stopped short of assigning a specific biochemical role for the protein, leaving it unclear whether the protease is directly involved in AIP maturation, or plays some other function in the agr signaling circuit, for example by modulating AIP sensing. Adding to the uncertainty, a recent study has even suggested that MroQ might hydrolyze the AIP, leading to the downstream inactivation of AgrC and by extension agr QS ( 38 ). Our biochemical studies clarify this picture by firmly establishing a direct role for MroQ in the second step of AIP biosynthesis, at least for agr groups I and II.…”

Section: Discussionmentioning

confidence: 99%

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Reconstitution of the S. aureus agr quorum sensing pathway reveals a direct role for the integral membrane protease MroQ in pheromone biosynthesis

Zhao

Bodine

Xie

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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In Staphylococcus aureus, virulence is under the control of a quorum sensing (QS) circuit encoded in the accessory gene regulator ( agr ) genomic locus. Key to this pathogenic behavior is the production and signaling activity of a secreted pheromone, the autoinducing peptide (AIP), generated following the ribosomal synthesis and posttranslational modification of a precursor polypeptide, AgrD, through two discrete cleavage steps. The integral membrane protease AgrB is known to catalyze the first processing event, generating the AIP biosynthetic intermediate, AgrD (1–32) thiolactone. However, the identity of the second protease in this biosynthetic pathway, which removes an N-terminal leader sequence, has remained ambiguous. Here, we show that membrane protease regulator of agr QS (MroQ), an integral membrane protease recently implicated in the agr response, is directly involved in AIP production. Genetic complementation and biochemical experiments reveal that MroQ proteolytic activity is required for AIP biosynthesis in agr specificity group I and group II, but not group III. Notably, as part of this effort, the biosynthesis and AIP-sensing arms of the QS circuit were reconstituted together in vitro. Our experiments also reveal the molecular features guiding MroQ cleavage activity, a critical factor in defining agr specificity group identity. Collectively, our study adds to the molecular understanding of the agr response and Staphylococcus aureus virulence.

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Section: In a Key Pair Of Studies Cosgriff Et Al And Marroquin Et Al ...mentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Reconstitution of the S. aureus agr quorum sensing pathway reveals a direct role for the integral membrane protease MroQ in pheromone biosynthesis

Zhao

Bodine

Xie

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…Coa acts as a mechanical barrier against phagocytosis by promoting plasma coagulation during infection. [27] In a previous study, only a few recruited white blood cells were found to engulf Staphylococcus in the abdominal cavity. This finding suggests that staphylococcus coagulation/clumping might provide a hypothesis for staphylococcus escape phagocytosis and clearance.…”

Section: Salicin Inhibits Coagulation In S Aureusmentioning

confidence: 94%

Inhibitory Effect of Salicin on Staphylococcus aureus Coagulase

Jiang,

Hou,

Liu

et al. 2023

ChemMedChem

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The massive use of antibiotics has resulted in an alarming increase in antibiotic resistance in Staphylococcus aureus (S. aureus). This study aimed to identify the inhibitory effect of salicin on S. aureus. Coagulase (Coa) activity was assessed using in vitro Coa assays and Western blot, thermal shift assay (TSA), fluorescence quenching and molecular docking experiments were conducted to verify the interaction between salicin and Coa. An in vivo mouse pneumonia model demonstrated that salicin can reduce the virulence of S. aureus. In vitro Coa assays elucidated that salicin directly inhibited Coa activity. The Western blot and TSA results suggested that salicin did not block the expression of Coa but affected the thermal stability of the protein by binding to Coa. The fluorescence quenching, molecular docking and molecular dynamics assays have found that the most promising binding site between salicin and Coa was GLN‐97. The pneumonia model of mice infected with S. aureus revealed that salicin could not only reduce the content of lung bacteria in mice but also prolong their survival. Salicin was identified as a novel anti‐infective candidate compound with the potential to target Coa and inhibit its activity by binding to it, which would facilitate the development of roadmaps for future research.

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Simple and accurate genomic classification model for distinguishing between human and pig Staphylococcus aureus

Zhou,

Du,

Ouyang

et al. 2024

Commun Biol

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cydA, spdC, and mroQ are novel genes involved in the plasma coagulation of Staphylococcus aureus

Cited by 5 publications

References 27 publications

Reconstitution of the S. aureus agr quorum sensing pathway reveals a direct role for the integral membrane protease MroQ in pheromone biosynthesis

Reconstitution of the S. aureus agr quorum sensing pathway reveals a direct role for the integral membrane protease MroQ in pheromone biosynthesis

Inhibitory Effect of Salicin on Staphylococcus aureus Coagulase

Simple and accurate genomic classification model for distinguishing between human and pig Staphylococcus aureus

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