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Objectives <p>This study aimed to investigate if the interspecies signalling could overcome the intrinsic colistin resistance observed in <i>Streptococcus pyogenes</i>.</p> Methods <p>We investigated the role of Oxo-C12-HSL (200µM) in altering resistance of <i>S. pyogenes</i> towards the colistin by determining MIC (minimum inhibitory concentration). To investigate the change in cell surface charge of <i>S. pyogenes</i> we performed gene expression analysis of <i>dlt</i>A and studied the binding of cationic protein cytochrome c (Cyt c) in presence of Oxo-C12-HSL. To investigate the observed increase in colistin sensitivity of <i>S. pyogenes</i> treated with Oxo-C12-HSL, we assessed changes in bacterial membrane permeability using propidium iodide (PI) staining and flow cytometry.</p> Results <p>It was observed that Oxo-C12-HSL, induced sensitivity in <i>S. pyogenes</i> towards colistin by lowering the MIC value by sixteen folds as compared to that of the control. The change in susceptibility of <i>S. pyogenes</i> towards colistin was found to be due to change in cell surface charge and alteration in membrane permeability. Gene expression of <i>dlt</i>A was found to be significantly (<i>p</i> ≤ 0.005) downregulated in the presence of Oxo-C12-HSL. This downregulation likely led to a more negatively charged cell surface, as evidenced by an increased binding of the cationic protein cytochrome c to <i>S. pyogenes</i>. Furthermore, flow cytometry analysis using propidium iodide staining revealed a significantly (<i>p</i> ≤ 0.0005) higher percentage of PI-positive cells in Oxo-C12-HSL treated <i>S. pyogenes</i>, demonstrating increased bacterial membrane permeability compared to untreated controls.</p> Conclusions <p>Colistin has limited activity against Gram-positive pathogens. It was deduced that the exposure of <i>S. pyogenes</i> to Oxo-C12-HSL caused alteration in cell surface charge and permeability, making it susceptible to colistin. This study demonstrates modulatory effects of interspecies signalling molecules on a Gram-positive pathogen, indicating a possible approach for repurposing current antibiotics or creating adjunctive therapies to fight <i>S. pyogenes</i> infections, particularly in the context of rising multidrug resistance.</p>

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Interspecies signaling can sensitize intrinsically resistant Streptococcus pyogenes to colistin

  • 期刊论文

  • 发表日期：

    2025年10月6日

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  • Amrita Bhagwat,
  • Hardik D. Rathod,
  • Sunil D. Saroj

摘要

Objectives

This study aimed to investigate if the interspecies signalling could overcome the intrinsic colistin resistance observed in Streptococcus pyogenes.

Methods

We investigated the role of Oxo-C12-HSL (200µM) in altering resistance of S. pyogenes towards the colistin by determining MIC (minimum inhibitory concentration). To investigate the change in cell surface charge of S. pyogenes we performed gene expression analysis of dltA and studied the binding of cationic protein cytochrome c (Cyt c) in presence of Oxo-C12-HSL. To investigate the observed increase in colistin sensitivity of S. pyogenes treated with Oxo-C12-HSL, we assessed changes in bacterial membrane permeability using propidium iodide (PI) staining and flow cytometry.

Results

It was observed that Oxo-C12-HSL, induced sensitivity in S. pyogenes towards colistin by lowering the MIC value by sixteen folds as compared to that of the control. The change in susceptibility of S. pyogenes towards colistin was found to be due to change in cell surface charge and alteration in membrane permeability. Gene expression of dltA was found to be significantly (p ≤ 0.005) downregulated in the presence of Oxo-C12-HSL. This downregulation likely led to a more negatively charged cell surface, as evidenced by an increased binding of the cationic protein cytochrome c to S. pyogenes. Furthermore, flow cytometry analysis using propidium iodide staining revealed a significantly (p ≤ 0.0005) higher percentage of PI-positive cells in Oxo-C12-HSL treated S. pyogenes, demonstrating increased bacterial membrane permeability compared to untreated controls.

Conclusions

Colistin has limited activity against Gram-positive pathogens. It was deduced that the exposure of S. pyogenes to Oxo-C12-HSL caused alteration in cell surface charge and permeability, making it susceptible to colistin. This study demonstrates modulatory effects of interspecies signalling molecules on a Gram-positive pathogen, indicating a possible approach for repurposing current antibiotics or creating adjunctive therapies to fight S. pyogenes infections, particularly in the context of rising multidrug resistance.