Small-Molecule Compound CY-158-11 Inhibits Staphylococcus aureus Biofilm Formation

Шен, Ли; Zhang, Jiao; Chen, Y.; Rao, Lulin; Wang, Xinyi; Zhao, Huabin; Wang, Bingjie; Xiao, Yanghua; Yu, Jingyi; Xu, Yanling; Jun-hong, Shi; Han, Wei; Song, Zengqiang; Yu, Fangyou

doi:10.1128/spectrum.00045-23

Cited by 6 publications

(5 citation statements)

References 38 publications

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“…In addition, it is required to study the influence of RSSMs on the bacteria considering the nonsterile environment in the oral cavity , The bacterial activity is studied in cultures after exposure to RSSMs. In colony counting on an agar plate, the colony forming units (CFUs) of S. mutans in the blank group and RSSM-2 group show no statistically significant difference (Figure d).…”

Section: Resultsmentioning

confidence: 99%

“…44 Streptococcus mutans (S. mutans), which is a common pathogen inhabiting the oral cavity, is selected to study the antibacterial effect of RSSMs. 45,46 The bacterial activity is studied in cultures after exposure to RSSMs. In colony counting on an agar plate, the colony forming units (CFUs) of S. mutans in the blank group and RSSM-2 group show no statistically significant difference (Figure 6d).…”

Section: Characterization Of Rssmsmentioning

confidence: 99%

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A Shear-Stiffening Mouthguard with Excellent Shock Absorption Capability and Remoldability via a Dynamic Dual Network

Zhou,

Wu,

Pan

et al. 2024

ACS Appl. Bio Mater.

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Mouthguards are used to reduce injuries and the probability of them to orofacial tissues when impacted during sports. However, the usage of a mouthguard is low due to the discomfort caused by the thickness of the mouthguard. Herein, we have constructed a dynamic dual network to fabricate a shear-stiffening mouthguard with remoldability, which are called remoldable shear-stiffening mouthguards (RSSMs). Based on diboron/oxygen dative bonds, RSSMs show a shearstiffening effect and excellent shock absorption ability, which can absorb more than 90% of the energy of a blank. Even reducing the thickness to half, RSSMs can reduce approximately 25% of the transmitted force and elongate by about 1.6-fold the buffer time compared to commercial mouthguard materials (Erkoflex and Erkoloc-pro). What is more, owing to the dynamic dual network, RSSMs show good remolding performance with unchanged shear-stiffening behavior and impact resistance, which conforms to the existing vacuum thermoforming mode. In addition, RSSMs exhibit stability in artificial saliva and biocompatibility. In conclusion, this work will broaden the range of mouthguard materials and offer a platform to apply shear-stiffening materials to biomedical applications and soft safeguarding devices.

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Section: Resultsmentioning

confidence: 99%

Section: Characterization Of Rssmsmentioning

confidence: 99%

A Shear-Stiffening Mouthguard with Excellent Shock Absorption Capability and Remoldability via a Dynamic Dual Network

Zhou,

Wu,

Pan

et al. 2024

ACS Appl. Bio Mater.

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“…Subsequently, we further observed the changes in membrane permeability through fluorescence microscopy and confocal laser scanning microscopy (CLSM). Cells stained with fluorescent nucleic acid stain SYTO 9 and PI exhibited green and red fluorescence, respectively. , SYTO 9 stains living and dead cells, and PI stains the DNA nucleus, emitting red fluorescence after embedding double-stranded DNA. PI is often used to detect apoptosis. , Compared with the LB broth control group and the monotherapy group, the combination group exhibited an increased red fluorescence, thereby indicating an increase in bacterial cell membrane permeability during early growth (2 h) (Supporting Figure S2).…”

Section: Resultsmentioning

confidence: 99%

“…Cell membrane permeability was examined through propidium iodide (PI) staining, 49 while SYTO 9 could stain both live and dead cells, as described previously, with modifications. 22,23 First, the cell suspension of K. pneumoniae FK6696 in the exponential phase (OD 600 ≈ 0.4) was treated with the test drug alone (BT 4 and 8 μg/mL; COL 1 μg/mL) or with the drug combination for 2 h and incubated at room temperature in PI (50 μg/mL) for 10 min. The fluorescence of PI reflected the cell wall and membrane integrity was observed under an inverted fluorescence microscope.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Bithionol Restores Sensitivity of Multidrug-Resistant Gram-Negative Bacteria to Colistin with Antimicrobial and Anti-biofilm Effects

et al. 2023

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Being among the few last-resort antibiotics, colistin (COL) has been used to treat severe infectious diseases, such as those caused by multidrugresistant Gram-negative bacteria (MDR GNB). However, the appearance of colistin-resistant (COL-R) GNB has been frequently reported. Therefore, novel antimicrobial strategies need to be urgently sought to address this resistance challenge. In the present study, antimicrobial drug screening conducted revealed that bithionol (BT), approved by the Food and Drug Administration and used as an anthelminthic drug for paragonimiasis, exhibited a synergistic antibacterial effect with COL. Clinically isolated COL-R GNB were used as candidates to evaluate the synergistic antibacterial activity. The results revealed that BT could significantly reverse the sensitivity of COL-R GNB to COL. Furthermore, the combined application of BT and COL can reduce bacterial biofilm formation and have a scavenging effect on the mature biofilm in vitro. The damage caused to the bacterial cell membrane integrity by the BT/COL combination was observed under a fluorescence microscope. The fluorescence intensity of reactive oxygen species also increased in the experimental group. The BT/COL combination also exhibited a synergistic antibacterial effect in vivo. Importantly, BT was confirmed to be safe at the highest concentrations that exerted synergistic effects on all tested strains. In conclusion, our findings demonstrated that BT exerted synergistic antimicrobial and anti-biofilm effects when combined with COL against MDR organisms, especially COL-R GNB, in vitro and in vivo. The findings thus provide a reference for the clinical response to the serious challenge of MDR GNB and the exploitation of the potential antibacterial activities of existing clinical non-antibacterial drugs.

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“…Indeed, a PubMed search carried out during the preparation of this manuscript using the search terms “biofilm,” “inhibitor,” and “ Staphylococcus aureus ” identified 525 publications, many of which describe compounds that were generated de novo and are not readily available. As an example, a recent report described the synthesis of a compound designated CY-158-11 that limited biofilm formation in multiple S. aureus strains at a concentration as low as 0.125 µg/mL ( 63 ). This effect was attributed to the reduced production of the polysaccharide intercellular adhesin resulting in reduced bacterial cell adhesion, but the expression of many of the S. aureus genes implicated in biofilm formation, including sarA , was also reduced.…”

Section: Discussionmentioning

confidence: 99%

Comparative evaluation of small molecules reported to be inhibitors of Staphylococcus aureus biofilm formation

Campbell,

Beenken,

Spencer

et al. 2024

Microbiol Spectr

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Biofilm formation is an important characteristic of many Staphylococcus aureus infections because it limits the efficacy of host defenses and conventional antibiotic therapy. There are many literature reports that describe small molecule inhibitors of S. aureus biofilm formation, but the lack of direct comparisons and differences in the methods used to assess inhibition make it impossible to assess the efficacy of these compounds relative to each other. To address this, we compared 19 compounds reported in the literature to be inhibitors of S. aureus biofilm formation. We used the methicillin-susceptible clinical osteomyelitis isolate UAMS-1 in a microtiter plate biofilm assay shown to maximize biofilm formation and provide results consistent with those observed in vivo . Under these conditions, telithromycin (Ketek) showed the greatest inhibitory activity, limiting biofilm formation to a degree comparable to a UAMS-1 sarA mutant at a concentration of 0.49 µM (0.40 µg/mL). Similar results were obtained for the methicillin-resistant USA300 strain LAC. Telithromycin is a bacteriostatic ketolide antibiotic that is not currently approved in the United States for use as an antibiotic due to its concerning safety profile. However, the concentration required to limit growth in vitro was higher than the concentration required to limit biofilm formation, suggesting that low-dose telithromycin might be useful to limit biofilm formation and increase the efficacy of other antibiotics in biofilm-associated infections. Irrespective of whether telithromycin is ultimately proven clinically useful in this regard, these results emphasize the need for widespread use of a standardized in vitro approach to evaluate prospective inhibitors. IMPORTANCE Because biofilm formation is such a problematic feature of Staphylococcus aureus infections, much effort has been put into identifying biofilm inhibitors. However, the results observed with these compounds are often reported in isolation, and the methods used to assess biofilm formation vary between labs, making it impossible to assess relative efficacy and prioritize among these putative inhibitors for further study. The studies we report address this issue by directly comparing putative biofilm inhibitors using a consistent in vitro assay. This assay was previously shown to maximize biofilm formation, and the results observed with this assay have been proven to be relevant in vivo . Of the 19 compounds compared using this method, many had no impact on biofilm formation under these conditions. Indeed, only one proved effective at limiting biofilm formation without also inhibiting growth.

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Small-Molecule Compound CY-158-11 Inhibits Staphylococcus aureus Biofilm Formation

Abstract: Most bacteria exist in the form of biofilms, often strongly adherent to various surfaces, causing bacterial resistance and chronic infections. In general, antibacterial drugs are not effective against biofilms.

Cited by 6 publications

References 38 publications

A Shear-Stiffening Mouthguard with Excellent Shock Absorption Capability and Remoldability via a Dynamic Dual Network

A Shear-Stiffening Mouthguard with Excellent Shock Absorption Capability and Remoldability via a Dynamic Dual Network

Bithionol Restores Sensitivity of Multidrug-Resistant Gram-Negative Bacteria to Colistin with Antimicrobial and Anti-biofilm Effects

Comparative evaluation of small molecules reported to be inhibitors of Staphylococcus aureus biofilm formation

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