Lactoferrin impairs type III secretory system function in enteropathogenic Escherichia coli

Area of Science:

• Microbiology
• Immunology
• Biochemistry

Background:

• Enteropathogenic Escherichia coli (EPEC) causes infant diarrhea, particularly in developing nations.
• EPEC utilizes a type III secretory system to inject effector proteins, leading to attaching and effacing lesions on host cells.
• Lactoferrin, found in human milk, is known to inhibit EPEC adherence to host cells.

Purpose of the Study:

• To investigate lactoferrin's effect on the initial host cell attachment step mediated by EPEC's type III secretory system.
• To elucidate the mechanism by which lactoferrin inhibits EPEC adherence and associated cellular damage.

Main Methods:

• Assessed EPEC-induced actin polymerization in HEp-2 cells.
• Measured EPEC-induced hemolytic activity.
• Quantified the secretion of E. coli secreted proteins A, B, and D (EspABD).
• Investigated the role of serine protease inhibitors in lactoferrin's inhibitory effect.

Main Results:

• Lactoferrin effectively blocked EPEC-mediated actin polymerization in HEp-2 cells.
• Lactoferrin inhibited EPEC-induced hemolysis.
• Lactoferrin induced the degradation of key secreted proteins, notably EspB, which are crucial for bacterial contact and pore formation.
• The proteolytic activity of lactoferrin was neutralized by serine protease inhibitors.

Conclusions:

• Lactoferrin disrupts the EPEC type III secretory system by degrading essential secreted proteins like EspB.
• This disruption inhibits bacterial adherence and associated cellular pathology.
• Lactoferrin holds potential for providing broad cross-protection against enteropathogens employing similar type III secretion mechanisms.