Antibacterial mechanism of rhodomyrtone involves the disruption of nucleoid segregation checkpoint in Streptococcus suis

Abstract

Rhodomyrtone has been recently demonstrated to possess a novel antibiotic mechanism of action against Grampositive bacteria which involved the multiple targets, resulting in the interference of several bacterial biological processes including the cell division. The present study aims to closely look at the downstream effect of rhodomyrtone treatment on nucleoid segregation in Streptococcus suis, an important zoonotic pathogen. The minimum inhibition concentration (MIC) and the minimum bactericidal concentration (MBC) values of rhodomyrtone against the recombinant S. suis ParB-GFP, a nucleoid segregation reporter strain, were 0.5 and 1 µg/ml, respectively, which were equivalent to the potency of vancomycin. Using the fluorescence live-cell imaging, we demonstrated that rhodomyrtone at 2× MIC caused incomplete nucleoid segregation and septum misplacement, leading to the generation of anucleated cells. FtsZ immune-staining of rhodomyrtone-treated S. suis for 30 min revealed that the large amount of FtsZ was trapped in the region of high fluidity membrane and appeared to be able to polymerize to form a complete Z-ring. However, the Z-ring was shifted away from the midcell. Transmission electron microscopy further confirmed the disruption of nucleoid segregation and septum misplacement at 120 min following the rhodomyrtone treatment. Asymmetric septum formation resulted in either generation of minicells without nucleoid, septum formed over incomplete segregated nucleoid (guillotine effect), or formation of multi-constriction of Z-ring within a single cell. This finding spotlights on antibacterial mechanism of rhodomyrtone involves the early stage in bacterial cell division process.

A LITERATURE REVIEW: THE POTENTIAL OF KARAMUNTING PLANT (Rhodomyrtus tomentosa) AS ANTIBACTERIAL AGENT

“…Rhodomyrtone also causes the release of ATP and cytoplasmic proteins which can interfere with the metabolic processes of bacterial cells. However, it is not known for sure how the direct effect of rhodomyrtone in the process of structural and physical cell changes that occur in bacteria (Traithan et al, 2020).…”

Rhodomyrtone Accumulates in Bacterial Cell Wall and Cell Membrane and Inhibits the Synthesis of Multiple Cellular Macromolecules in Epidemic Methicillin-Resistant Staphylococcus aureus

“…The minimum inhibitory and minimum bactericidal concentrations of rhodomyrtone were previously reported to be 0.5/0.5 µg/mL for EMRSA-16 and 0.5/1 µg/mL for S. aureus ATCC 29213 [ 23 ]. The antibacterial activities of rhodomyrtone have previously been demonstrated against several Gram-positive bacterial isolates, including S. aureus and S. epidermidis (MIC = 0.25–2 µg/mL) [ 24 ], Propionibacterium acnes (MIC = 0.12–0.5 µg/mL) [ 25 ], Streptococcus pneumoniae (MIC = 0.125–1 µg/mL) [ 26 ], S. aureus (MIC = 1.83 µg/mL) [ 27 ], Streptococcus suis (MIC = 0.5 µg/mL) [ 28 ], and Clostridium difficile (MIC = 0.625–2.5 µg/mL) [ 19 ]. The antibacterial activity of rhodomyrtone against P. acnes was reported to be comparable with that of the standard antibiotic erythromycin [ 25 ], and with that of vancomycin for S. aureus, and C. difficile [ 19 , 23 ].…”

“…Previous studies have demonstrated that rhodomyrtone is a membrane-active compound [ 29 ]. The interaction of rhodomyrtone with the bacterial cell wall and membrane resulted in membrane invagination, which has been demonstrated as possible mechanism of rhodomyrtone mediated membrane distortion [ 21 , 28 ]. The presence of rhodomyrtone in cytoplasmic extracts might be due to the capability of rhodomyrtone to penetrate the cytoplasm of the cells.…”

“…Transcriptional analysis of MRSA exposed to subinhibitory concentrations of rhodomyrtone revealed interference with gene expression, resulting in the induction of 64 genes and repression of 35 genes, with changes in genes encoding essential proteins involved in amino acid metabolism, membrane function, ATP-binding cassette transportation, lipoprotein, and nucleotide metabolism [ 22 ]. An incomplete nucleoid segregation and septum misplacement was observed in Streptococcus suis after treatment with rhodomyrtone [ 28 ]. Rhodomyrtone has also been reported to interfere with the expression of virulence genes and to disrupt sigB [ 33 ].…”