Antimicrobial Effect of Asiatic Acid Against Clostridium difficile Is Associated With Disruption of Membrane Permeability

Harnvoravongchai, Phurt; Chankhamhaengdecha, Surang; Ounjai, Puey; Singhakaew, Sombat; Boonthaworn, Kanpong; Janvilisri, Tavan

doi:10.3389/fmicb.2018.02125

Cited by 25 publications

(19 citation statements)

References 56 publications

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“…C. difficile strain R20291 was kindly provided by Prof Nigel Minton, University of Nottingham. As described previously [ 40 , 41 ], all C. difficile strains were grown at 37 °C in an anaerobic workstation (85% N 2 , 10% H 2 , and 5% CO 2 ; Don Whitley Scientific, UK) in the brain heart infusion supplemented with 0.1% ( w / v ) sodium taurocholate, 0.1% L-cysteine, and 5 mg/mL yeast extract broth or agar (BHIS).…”

Section: Methodsmentioning

confidence: 99%

Teicoplanin Suppresses Vegetative Clostridioides difficile and Spore Outgrowth

et al. 2021

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In recent decades, the incidence of Clostridioides difficile infection (CDI) has remained high in both community and health-care settings. With the increasing rate of treatment failures and its ability to form spores, an alternative treatment for CDI has become a global priority. We used the microdilution assay to determine minimal inhibitory concentrations (MICs) of vancomycin and teicoplanin against 30 distinct C. difficile strains isolated from various host origins. We also examined the effect of drugs on spore germination and outgrowth by following the development of OD600. Finally, we confirmed the spore germination and cell stages by microscopy. We showed that teicoplanin exhibited lower MICs compared to vancomycin in all tested isolates. MICs of teicoplanin ranged from 0.03–0.25 µg/mL, while vancomycin ranged from 0.5–4 µg/mL. Exposure of C. difficile spores to broth supplemented with various concentrations of antimicrobial agents did not affect the initiation of germination, but the outgrowth to vegetative cells was inhibited by all test compounds. This finding was concordant with aberrant vegetative cells after antibiotic treatment observed by light microscopy. This work highlights the efficiency of teicoplanin for treatment of C. difficile through prevention of vegetative cell outgrowth.

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Section: Methodsmentioning

confidence: 99%

Teicoplanin Suppresses Vegetative Clostridioides difficile and Spore Outgrowth

et al. 2021

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“…The ability of membrane disruption was suggested for zingerone, menthol, and trans-cinnamaldehyde[ 61 ]. Asiatic acid, an active triterpenoid derived from Centella asiatica , exhibited significant antimicrobial activity against C. difficile strains isolated from different sources by disrupting the cytoplasmic membrane with MICs of 10–20 µg/mL[ 62 ]. Lauric acid, an active component found in virgin coconut oil, exhibited anticlostridial activity at a 250-µmol/L concentration through the membrane disruption mechanism[ 63 ].…”

Section: Natural Products Serve As a Good Source Of Anti-clostridial Activitiesmentioning

confidence: 99%

Frontiers in antibiotic alternatives for Clostridioides difficile infection

Phanchana¹,

Harnvoravongchai²,

Wongkuna³

et al. 2021

WJG

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Clostridioides difficile ( C. difficile ) is a gram-positive, anaerobic spore-forming bacterium and a major cause of antibiotic-associated diarrhea. Humans are naturally resistant to C. difficile infection (CDI) owing to the protection provided by healthy gut microbiota. When the gut microbiota is disturbed, C. difficile can colonize, produce toxins, and manifest clinical symptoms, ranging from asymptomatic diarrhea and colitis to death. Despite the steady-if not rising-prevalence of CDI, it will certainly become more problematic in a world of antibiotic overuse and the post-antibiotic era. C. difficile is naturally resistant to most of the currently used antibiotics as it uses multiple resistance mechanisms. Therefore, current CDI treatment regimens are extremely limited to only a few antibiotics, which include vancomycin, fidaxomicin, and metronidazole. Therefore, one of the main challenges experienced by the scientific community is the development of alternative approaches to control and treat CDI. In this Frontier article, we collectively summarize recent advances in alternative treatment approaches for CDI. Over the past few years, several studies have reported on natural product-derived compounds, drug repurposing, high-throughput library screening, phage therapy, and fecal microbiota transplantation. We also include an update on vaccine development, pre- and pro-biotics for CDI, and toxin antidote approaches. These measures tackle CDI at every stage of disease pathology via multiple mechanisms. We also discuss the gaps and concerns in these developments. The next epidemic of CDI is not a matter of if but a matter of when. Therefore, being well-equipped with a collection of alternative therapeutics is necessary and should be prioritized.

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“…Biofilm formation assay. Biofilms of C. difficile were generated as mentioned previously with some modifications 33,34 . Briefly, an overnight culture of C. difficile strain R20291 was diluted 100-fold into fresh BHIY supplemented with 0.1 M glucose and various concentrations of ticagrelor and incubated in 24-well plate for 48 h at 37 °C.…”

Section: Time-kill Assaymentioning

confidence: 99%

Repurposing a platelet aggregation inhibitor ticagrelor as an antimicrobial against Clostridioides difficile

Phanchana

Phetruen

Harnvoravongchai

et al. 2020

Sci Rep

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Drug resistance in Clostridioides difficile becomes a public health concern worldwide, especially as the hypervirulent strains show decreased susceptibility to the first-line antibiotics for C. difficile treatment. Therefore, the simultaneous discovery and development of new compounds to fight this pathogen are urgently needed. in order to determinate new drugs active against C. difficile, we identified ticagrelor, utilized for the prevention of thrombotic events, as exhibiting potent growth-inhibitory activity against C. difficile. Whole-cell growth inhibition assays were performed and compared to vancomycin and metronidazole, followed by determining time-kill kinetics against C. difficile. Activities against biofilm formation and spore germination were also evaluated. Leakage analyses and electron microscopy were applied to confirm the disruption of membrane structure. Finally, ticagrelor's ability to synergize with vancomycin and metronidazole was determined using checkerboard assays. our data showed that ticagrelor exerted activity with a MIC range of 20-40 µg/mL against C. difficile. this compound also exhibited an inhibitory effect on biofilm formation and spore germination. Additionally, ticagrelor did not interact with vancomycin nor metronidazole. Our findings revealed for the first time that ticagrelor could be further developed as a new antimicrobial agent for fighting against C. difficile.A Gram-positive, spore-forming bacterium Clostridioides difficile, formerly known as Clostridium difficile is currently one of the most concerning nosocomial pathogens 1 . C. difficile tops the list of nosocomial infections with the annual estimation of more than 200,000 cases and $1 billion healthcare costs in the United States alone 2 . It has been postulated that C. difficile infection (CDI) in humans may come from animals as an overlap between human and animal isolates has been observed 3 . Patients with CDI can appear asymptomatic, however, the excessive use of antibiotics can cause an alteration in indigenous gut microbiota, enabling C. difficile to populate, produce toxins and become pathogenic, thereby causing severe diarrhoea, pseudomembranous colitis and occasionally fatality, especially in patients aged more than 65 4 . The treatment for CDI is currently limited to vancomycin, metronidazole, and fidaxomicin 5 , however, increase in treatment failures CDI due to recurrence has rendered these antibiotics ineffective 6 . Although metronidazole was initially used as the first-line agent for treatment of non-severe CDI cases and vancomycin was a drug of choice for more severe and recurrent CDI 4 , however, recent guidelines from the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) suggests that either vancomycin or fidaxomicin is recommended over metronidazole for an initial episode of CDI, unless in the setting where access to these drugs are limited 5-7 . Emergence of resistant strains to these antibiotics has been demonstrated, causing reduction in t...

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Antimicrobial Effect of Asiatic Acid Against Clostridium difficile Is Associated With Disruption of Membrane Permeability

Cited by 25 publications

References 56 publications

Teicoplanin Suppresses Vegetative Clostridioides difficile and Spore Outgrowth

Teicoplanin Suppresses Vegetative Clostridioides difficile and Spore Outgrowth

Frontiers in antibiotic alternatives for Clostridioides difficile infection

Repurposing a platelet aggregation inhibitor ticagrelor as an antimicrobial against Clostridioides difficile

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