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Updated: Aug 18, 2026

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
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
Abstract:
The role played by host-pathogen interactions in regulation of expression of streptococcal virulence factors in vivo is beginning to become clear. We have reported that the expression of 2 streptococcal virulence factors, the streptococcal pyrogenic exotoxin (Spe) A and the cysteine protease SpeB, was reciprocally modulated during infection with Streptococcus pyogenes. To identify host signals mediating this reciprocal regulation, we cocultured clonal M1T1 isolates with human peripheral blood mononuclear cells (PBMCs). In accordance with our in vivo findings, when bacteria were in direct contact with human PBMCs or were separated in transwells, expression of speA was induced, whereas expression of speB was down-regulated. This phenomenon was mediated by transferrin and lactoferrin and was influenced by the iron-saturation status of these proteins. Iron chelation from media induced expression of speA, but to a much lesser degree than did that with apotransferrin and lactoferrin, suggesting additional effects of these ferrins on modulation of expression of speA and speB. Thus, ferrins may play an important role in host-pathogen interactions in skin and mucosal tissues.
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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