Immunomodulatory and Protective Roles of Quorum-Sensing Signaling Molecules N -Acyl Homoserine Lactones during Infection of Mice with Aeromonas hydrophila

Abstract

Aeromonas hydrophila leads to both intestinal and extraintestinal infections in animals and humans, and the underlying mechanisms leading to mortality are largely unknown. By using a septicemic mouse model of infection, we showed that animals challenged with A. hydrophila die because of kidney and liver damage, hypoglycemia, and thrombocytopenia. Pretreatment of animals with quorum-sensing-associated signaling molecules N-acyl homoserine lactones (AHLs), such as butanoyl and hexanoyl homoserine lactones (C 4 -and C 6 -HSLs), as well as N-3-oxododecanoyl (3-oxo-C 12 )-HSL, prevented clinical sequelae, resulting in increased survivability of mice. Since little is known as to how different AHLs modulate the immune response during infection, we treated mice with the above AHLs prior to lethal A. hydrophila infection. When we compared results in such animals to those in controls, the treated animals exhibited a significantly reduced bacterial load in the blood and other mouse organs, as well as various levels of cytokines/chemokines. Importantly, neutrophil numbers were significantly elevated in the blood of C 6 -HSL-treated mice compared to those in animals given phosphate-buffered saline and then infected with the bacteria. These findings coincided with the fact that neutropenic animals were more susceptible to A. hydrophila infection than normal mice. Our data suggested that neutrophils quickly cleared bacteria by either phagocytosis or possibly another mechanism(s) during infection. In a parallel study, we indeed showed that other predominant immune cells inflicted during A. hydrophila infections, such as murine macrophages, when they were pretreated with AHLs, rapidly phagocytosed bacteria, whereas untreated cells phagocytosed fewer bacteria. This study is the first to report that AHL pretreatment modulates the innate immune response in mice and enhances their survivability during A. hydrophila infection.

The Social Life of Aeromonas through Biofilm and Quorum Sensing Systems

“…Khajanchi et al (2011) have reported a similar immune-modulatory effect with C4-HSL, C6-HSL, and N-3-oxo-C12-HSL in septicemic mice infected with A. hydrophila { A. dhakensis }. Indeed, AHL-based pretreatment was associated with reduced levels of cytokines/chemokines in tissues, increased neutrophil recruitment from blood (C6-HSL), enhanced bacterial clearance, limitation of clinical symptoms, and increase in survivability for infected mice.…”

“…In addition, the AHL-based pretreatment increased in vitro bacterial phagocytosis by murine macrophages. Thus, it seems that exogenous AHLs act as a signal for the activation of host response to infection (Khajanchi et al, 2011). Both promising QS inhibitors that interfere with aeromonad QS, e.g., menthol (Husain et al, 2015), and some purified QS molecules (Khajanchi et al, 2011), represent new therapeutic perspectives to fight against aeromonosis threatening multi-drug antibiotic resistance.…”

Does diversity of environmental microbial exposure matter for the occurrence of allergy and asthma?

“…They are known to have antimicrobial, pharmacologic, and immunomodulatory activities. 75,76 The profile of these molecules at any given time might reflect the status of a microbial community. This opens new areas of research in environmental exposure to microorganisms.…”

Quorum Sensing: A Prospective Therapeutic Target for Bacterial Diseases

“…C4-and C6-HSLs, 3-oxo-C12-HSL Regulating the host immune receptor Increased survivability of infected mice [59] 4.2. QS Signals Synthesis Inhibition.…”