In vivo evaluation of a recombinant N-acylhomoserine lactonase formulated in a hydrogel using a murine model infected with MDR Pseudomonas aeruginosa clinical isolate, CCASUP2

Abstract

Failure in the treatment of P. aeruginosa, due to its broad spectrum of resistance, has been associated with increased patient mortality. One alternative approach for infection control is quorum quenching which was found to decrease virulence of such pathogen. In this study, the efficiency of a recombinant Ahl-1 lactonase formulated as a hydrogel was investigated to control the infection of multidrug resistant (MDR) P. aeruginosa infected burn using a murine model. The recombinant N-acylhomoserine lactonase (Ahl-1) was formulated as a hydrogel. To test its ability to control the infection of MDR P. aeruginosa, a thermal injury model was used. Survival rate, and systemic spread of the infection were evaluated. Histopathological examination of the animal dorsal skin was also done for monitoring the healing and cellular changes at the site of infection. Survival rate in the treated group was 100% relative to 40% in the control group. A decrease of up to 3 logs of bacterial count in the blood samples of the treated animals relative to the control group and a decrease of up to 4 logs and 2.3 logs of bacteria in lung and liver samples, respectively were observed. Histopathological examination revealed more enhanced healing process in the treated group. Accordingly, by promoting healing of infected MDR P. aeruginosa burn and by reducing systemic spread of the infection as well as decreasing mortality rate, Ahl-1 hydrogel application is a promising strategy that can be used to combat and control P. aeruginosa burn infections.

Supplemental N-acyl homoserine lactonase alleviates intestinal disruption and improves gut microbiota in broilers challenged by Salmonella Typhimurium

“…Toll-like receptor 5 and inducible nitric oxide synthase) and anti-inflammatory cytokine IL-10 in zebrafish infected with Aeromonas hydrophila [ 11 ]. Similar findings were obtained in several other studies where AHLase treatment repressed Pseudomonas aeruginosa (a typical Gram-negative pathogen) infection and blocked its ability to induce inflammatory injuries and mortality of mice [ 12 , 13 ]. As a result, AHLase treatment represents a promising candidate for use as an approach against S. Typhimurium infection in animals.…”

“…In this study, we found a time-dependent alteration of ileal IL-1β, IL-8 and TNF-α expression responding to S. Typhimurium challenge, confirming a complicated impact of S. Typhimurium on the expression profile of intestinal inflammatory cytokines presumptively due to the intricate immune feedbacks of host [31]. It is known that AHLase can weaken the pathogenicity and infectivity of certain Gram-negative pathogens by restraining their physiological activities such as biofilm formation and toxin secretion [10][11][12][13][14][15]. Specially, it was found to reverse Pseudomonas aeruginosa-induced acute pneumonia by alleviating inflammatory cytokines expression in mice [12].…”

The Role of Quorum Sensing Molecules in Bacterial–Plant Interactions

“…The efficacy of recombinant lactonase in the form of a hydrogel in controlling burn wound infections caused by a multidrug-resistant (MDR) strain of Pseudomonas aeruginosa was also demonstrated. These observations raise hopes for a new strategy to eradicate and control wound infections caused by P. aeruginosa [ 100 ]. Another interesting example is the use of the recombinant lactonase Ai-iAQSI-1 from Bacillus sp.…”

Formulation and Biological Evaluation of Quorum Sensing Inhibitor-Based Nanoemulsion against Resistant Pseudomonal Infections

“…After completion of the study, the animals were sacrificed by intraperitoneal injection of pentobarbital sodium (1 mL/5 kg body weight). A third-degree burn wound infection model was developed with P. aeruginosa strain (PAO1) in rats as described by Sakr et al [38]. Wistar rats were grouped into 5 groups (6 rats each).…”