Pub Date : 2024-09-10DOI: 10.1038/s41429-024-00771-x
Ekaterina A. Chingizova, Artur R. Chingizov, Ekaterina S. Menchinskaya, Evgeny A. Pislyagin, Aleksandra S. Kuzmich, Elena V. Leshchenko, Gleb V. Borkunov, Irina V. Guzhova, Dmitry L. Aminin, Ekaterina A. Yurchenko
A new biological activity was discovered for marine fungal meroterpenoid meroantarctine A with unique 6/5/6/6 polycyclic system. It was found that meroantarctine A can significantly reduce biofilm formation by Staphylococcus aureus with an IC50 of 9.2 µM via inhibition of sortase A activity. Co-cultivation of HaCaT keratinocytes with a S. aureus suspension was used as an in vitro model of skin infection. Treatment of S. aureus-infected HaCaT cells with meroantarctine A at 10 µM caused a reduction in the production of TNF-α, IL-18, NO, and ROS, as well as LDH release and caspase 1 activation in these cells and, finally, recovered the proliferation and migration of HaCaT cells in an in vitro wound healing assay up to the control level. Thus, meroantarctine A is a new promising antibiofilm compound which can effective against S. aureus caused skin infection.
研究发现了海洋真菌美仑塔辛 A 的一种新生物活性，它具有独特的 6/5/6/6 多环系统。研究发现 Meroantarctine A 能通过抑制分类酶 A 的活性显著减少金黄色葡萄球菌生物膜的形成，IC50 为 9.2 µM。将 HaCaT 角质细胞与金黄色葡萄球菌悬浮液共同培养作为皮肤感染的体外模型。用 10 µM 的美罗安他克汀 A 处理被金黄色葡萄球菌感染的 HaCaT 细胞，可减少这些细胞中 TNF-α、IL-18、NO 和 ROS 的产生，并减少 LDH 的释放和 caspase 1 的激活，最后在体外伤口愈合试验中使 HaCaT 细胞的增殖和迁移恢复到对照水平。因此，美罗安亭 A 是一种新型的抗生物膜化合物，可有效对抗金黄色葡萄球菌引起的皮肤感染。
{"title":"The influence of marine fungal meroterpenoid meroantarctine A toward HaCaT keratinocytes infected with Staphylococcus aureus","authors":"Ekaterina A. Chingizova, Artur R. Chingizov, Ekaterina S. Menchinskaya, Evgeny A. Pislyagin, Aleksandra S. Kuzmich, Elena V. Leshchenko, Gleb V. Borkunov, Irina V. Guzhova, Dmitry L. Aminin, Ekaterina A. Yurchenko","doi":"10.1038/s41429-024-00771-x","DOIUrl":"https://doi.org/10.1038/s41429-024-00771-x","url":null,"abstract":"<p>A new biological activity was discovered for marine fungal meroterpenoid meroantarctine A with unique 6/5/6/6 polycyclic system. It was found that meroantarctine A can significantly reduce biofilm formation by <i>Staphylococcus aureus</i> with an IC<sub>50</sub> of 9.2 µM via inhibition of sortase A activity. Co-cultivation of HaCaT keratinocytes with a <i>S. aureus</i> suspension was used as an in vitro model of skin infection. Treatment of <i>S. aureus-</i>infected HaCaT cells with meroantarctine A at 10 µM caused a reduction in the production of TNF-α, IL-18, NO, and ROS, as well as LDH release and caspase 1 activation in these cells and, finally, recovered the proliferation and migration of HaCaT cells in an in vitro wound healing assay up to the control level. Thus, meroantarctine A is a new promising antibiofilm compound which can effective against <i>S. aureus</i> caused skin infection.</p>","PeriodicalId":501839,"journal":{"name":"The Journal of Antibiotics","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142179619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-17DOI: 10.1038/s41429-024-00722-6
H. Hashizume, Shigeko Harada, R. Sawa, K. Iijima, Y. Kubota, Y. Shibuya, Ryoko Nagasaka, Masaki Hatano, Masayuki Igarashi
{"title":"Correction: New chloptosins B and C from an Embleya strain exhibit synergistic activity against methicillin-resistant Staphylococcus aureus when combined with co-producing compound L-156,602.","authors":"H. Hashizume, Shigeko Harada, R. Sawa, K. Iijima, Y. Kubota, Y. Shibuya, Ryoko Nagasaka, Masaki Hatano, Masayuki Igarashi","doi":"10.1038/s41429-024-00722-6","DOIUrl":"https://doi.org/10.1038/s41429-024-00722-6","url":null,"abstract":"","PeriodicalId":501839,"journal":{"name":"The Journal of Antibiotics","volume":"36 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140965254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-19DOI: 10.1038/s41429-023-00687-y
Alison H. Araten, Rachel S. Brooks, Sarah D. W. Choi, Laura L. Esguerra, Diana Savchyn, Emily J. Wu, Gabrielle Leon, Katherine J. Sniezek, Mark P. Brynildsen
Cephalosporins comprise a β-lactam antibiotic class whose first members were discovered in 1945 from the fungus Cephalosporium acremonium. Their clinical use for Gram-negative bacterial infections is widespread due to their ability to traverse outer membranes through porins to gain access to the periplasm and disrupt peptidoglycan synthesis. More recent members of the cephalosporin class are administered as last resort treatments for complicated urinary tract infections, MRSA, and other multi-drug resistant pathogens, such as Neisseria gonorrhoeae. Unfortunately, there has been a global increase in cephalosporin-resistant strains, heteroresistance to this drug class has been a topic of increasing concern, and tolerance and persistence are recognized as potential causes of cephalosporin treatment failure. In this review, we summarize the cephalosporin antibiotic class from discovery to their mechanisms of action, and discuss the causes of cephalosporin treatment failure, which include resistance, tolerance, and phenomena when those qualities are exhibited by only small subpopulations of bacterial cultures (heteroresistance and persistence). Further, we discuss how recent efforts with cephalosporin conjugates and combination treatments aim to reinvigorate this antibiotic class.
{"title":"Cephalosporin resistance, tolerance, and approaches to improve their activities","authors":"Alison H. Araten, Rachel S. Brooks, Sarah D. W. Choi, Laura L. Esguerra, Diana Savchyn, Emily J. Wu, Gabrielle Leon, Katherine J. Sniezek, Mark P. Brynildsen","doi":"10.1038/s41429-023-00687-y","DOIUrl":"https://doi.org/10.1038/s41429-023-00687-y","url":null,"abstract":"<p>Cephalosporins comprise a β-lactam antibiotic class whose first members were discovered in 1945 from the fungus <i>Cephalosporium acremonium</i>. Their clinical use for Gram-negative bacterial infections is widespread due to their ability to traverse outer membranes through porins to gain access to the periplasm and disrupt peptidoglycan synthesis. More recent members of the cephalosporin class are administered as last resort treatments for complicated urinary tract infections, MRSA, and other multi-drug resistant pathogens, such as <i>Neisseria gonorrhoeae</i>. Unfortunately, there has been a global increase in cephalosporin-resistant strains, heteroresistance to this drug class has been a topic of increasing concern, and tolerance and persistence are recognized as potential causes of cephalosporin treatment failure. In this review, we summarize the cephalosporin antibiotic class from discovery to their mechanisms of action, and discuss the causes of cephalosporin treatment failure, which include resistance, tolerance, and phenomena when those qualities are exhibited by only small subpopulations of bacterial cultures (heteroresistance and persistence). Further, we discuss how recent efforts with cephalosporin conjugates and combination treatments aim to reinvigorate this antibiotic class.</p>","PeriodicalId":501839,"journal":{"name":"The Journal of Antibiotics","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138818829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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