Modulation of expression of superantigens by human transferrin and lactoferrin: a novel mechanism in

Rita G Kansal1, Ramy K Aziz, Malak Kotb

  • 1Veterans Affairs Medical Center, Research Service, and Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee 38104, USA. rkansal@utmem.edu

Insights

Host proteins transferrin and lactoferrin regulate Streptococcus pyogenes virulence factors. These ferrins modulate streptococcal pyrogenic exotoxin A (SpeA) and cysteine protease (SpeB) expression, impacting host-pathogen interactions.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • Host-pathogen interactions are crucial for regulating bacterial virulence factor expression.
  • Streptococcus pyogenes virulence factors, SpeA and SpeB, exhibit reciprocal modulation during infection.

Purpose of the Study:

  • To identify host-derived signals that mediate the reciprocal regulation of SpeA and SpeB expression in Streptococcus pyogenes.
  • To elucidate the role of host proteins in modulating streptococcal virulence factor expression.

Main Methods:

  • Coculturing of Streptococcus pyogenes M1T1 isolates with human peripheral blood mononuclear cells (PBMCs).
  • Utilizing transwell systems to assess bacterial-host cell contact-dependent and independent signaling.
  • Investigating the influence of transferrin and lactoferrin, and their iron-saturation status, on virulence gene expression.

Main Results:

  • Direct contact or transwell co-culture with PBMCs induced SpeA expression and down-regulated SpeB expression in Streptococcus pyogenes.
  • Transferrin and lactoferrin were identified as key mediators of this reciprocal regulation.
  • Iron chelation alone induced SpeA expression less effectively than apotransferrin and lactoferrin, suggesting additional ferrin-mediated effects.

Conclusions:

  • Ferrins, such as transferrin and lactoferrin, play a significant role in modulating Streptococcus pyogenes virulence factor expression during host-pathogen interactions.
  • These findings highlight the importance of ferrins in the context of skin and mucosal infections.
  • Understanding these interactions can inform strategies for managing streptococcal infections.

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