Cinnamaldehyde Inhibits Staphylococcus aureus Virulence Factors and Protects against Infection in a Galleria mellonella Model

Abstract

Bacterial resistance to the available marketed drugs has prompted the search of novel therapies; especially in regards of anti-virulence strategies that aim to make bacteria less pathogenic and/or decrease their probability to become resistant to therapy. Cinnamaldehyde is widely known for its antibacterial properties through mechanisms that include the interaction of this compound with bacterial cell walls. However, only a handful of studies have addressed its effects on bacterial virulence, especially when tested at sub-inhibitory concentrations. Herein, we show for the first time that cinnamaldehyde is bactericidal against Staphylococcus aureus and Enterococcus faecalis multidrug resistant strains and does not promote bacterial tolerance. Cinnamaldehyde actions were stronger on S. aureus as it was able to inhibit its hemolytic activity on human erythrocytes and reduce its adherence to latex. Furthermore, cinnamaldehyde enhanced the serum-dependent lysis of S. aureus. In vivo testing of cinnamaldehyde in Galleria mellonella larvae infected with S. aureus, showed this compound improves larvae survival whilst diminishing bacterial load in their hemolymph. We suggest that cinnamaldehyde may represent an alternative therapy to control S. aureus-induced bacterial infections as it presents the ability to reduce bacterial virulence/survival without promoting an adaptive phenotype.

Effect of trans-Cinnamaldehyde on Methicillin-Resistant Staphylococcus aureus Biofilm Formation: Metabolic Activity Assessment and Analysis of the Biofilm-Associated Genes Expression

“…Our results are similar to those obtained by Ferro et al [22], who also found that 1/2 MIC of TC reduced S. aureus metabolic activity in biofilm. In our study, reduction of metabolic activity in the presence of TC at 1/2 MBIC reached over 50%.…”

“…Variability between clinical isolates was also observed in other studies-MIC of TC for S. epidermidis isolates were 400-500 µg/mL [29]. Other research concerning antimicrobial activity of TC showed that MIC values for S. aureus isolates were higher than in our study (250 µg/mL) [22]. These results support our findings, showing diversity in the sensitivity on TC within the species.…”

“…Ribeiro et al [21], by using a fibroblast cell line, showed that TC did not compromise fibroblast cell viability. Ferro et al [22], who investigated influence of TC on the survival of Galleria mellonella larvae infected with S. aureus, showed that this compound improved larval survival due to a reduction of bacterial load in their hemolymph, and obtained no results indicating the toxic effect of TC in doses equivalent to 25-50 mg/kg.…”

Galleria mellonella as a consolidated in vivo model hosts: New developments in antibacterial strategies and novel drug testing

“…Another phytochemical, namely cinnamaldehyde, the predominant active compound found in cinnamon oil from the stem bark of the Cinnamomum cassia, was found not to induce any toxicity and enhanced the survival rate of larvae when they when infected by S. aureus ATCC 25923. Moreover, cinnamaldehyde significantly reduced the number of bacteria in larvae hemolymph in comparison with that in those in the untreated groups [77].…”

Evaluation of the antimicrobial activity of Cinnamomum zeylanicum essential oil and trans-Cinnamaldehyde against resistant Mycobacterium tuberculosis

“…Extracts and EOs of C. zeylanicum exhibit significant antimicrobial activities against several organisms, including the fungus Aspergillus (GOMEZ et al, 2018), M. tuberculosis (MOTA et al, 2018), gram-positive bacteria, (WIWATTANARATTANABUT et al, 2017), and gram-negative bacteria (LIU et al, 2017). The antibacterial activity of TCin has also been evaluated against several gram-negative bacteria (UTCHARIYAKIAT et al, 2016), gram-positive bacteria, (FERRO et al, 2016), and H37Rv strain of M. tuberculosis (ANDRADE-OCHOA et al, 2015;POLAQUINI et al, 2017). However, the antimycobacterial activities of CzeyEO and TCin have not been assessed against sensitive and resistant clinical isolates of M. tuberculosis.…”