Patrick Hsien-Neng Kao, Jun-Hong Ch'ng, Kelvin K L Chong, Claudia J Stocks, Siu Ling Wong, Kimberly A Kline
{"title":"<i>Enterococcus faecalis</i> suppresses <i>Staphylococcus aureus</i>-induced NETosis and promotes bacterial survival in polymicrobial infections.","authors":"Patrick Hsien-Neng Kao, Jun-Hong Ch'ng, Kelvin K L Chong, Claudia J Stocks, Siu Ling Wong, Kimberly A Kline","doi":"10.1093/femsmc/xtad019","DOIUrl":null,"url":null,"abstract":"<p><p><i>Enterococcus faecalis</i> is an opportunistic pathogen that is frequently co-isolated with other microbes in wound infections. While <i>E. faecalis</i> can subvert the host immune response and promote the survival of other microbes via interbacterial synergy, little is known about the impact of <i>E. faecalis</i>-mediated immune suppression on co-infecting microbes. We hypothesized that <i>E. faecalis</i> can attenuate neutrophil-mediated responses in mixed-species infection to promote survival of the co-infecting species. We found that neutrophils control <i>E. faecalis</i> infection via phagocytosis, ROS production, and degranulation of azurophilic granules, but it does not trigger neutrophil extracellular trap formation (NETosis). However, <i>E. faecalis</i> attenuates <i>Staphylococcus aureus</i>-induced NETosis in polymicrobial infection by interfering with citrullination of histone, suggesting <i>E. faecalis</i> can actively suppress NETosis in neutrophils. Residual <i>S. aureus</i>-induced NETs that remain during co-infection do not impact <i>E. faecalis</i>, further suggesting that <i>E. faecalis</i> possess mechanisms to evade or survive NET-associated killing mechanisms. <i>E. faecalis</i>-driven reduction of NETosis corresponds with higher <i>S. aureus</i> survival, indicating that this immunomodulating effect could be a risk factor in promoting the virulence polymicrobial infection. These findings highlight the complexity of the immune response to polymicrobial infections and suggest that attenuated pathogen-specific immune responses contribute to pathogenesis in the mammalian host.</p>","PeriodicalId":73024,"journal":{"name":"FEMS microbes","volume":"4 ","pages":"xtad019"},"PeriodicalIF":0.0000,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10608956/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FEMS microbes","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/femsmc/xtad019","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Enterococcus faecalis is an opportunistic pathogen that is frequently co-isolated with other microbes in wound infections. While E. faecalis can subvert the host immune response and promote the survival of other microbes via interbacterial synergy, little is known about the impact of E. faecalis-mediated immune suppression on co-infecting microbes. We hypothesized that E. faecalis can attenuate neutrophil-mediated responses in mixed-species infection to promote survival of the co-infecting species. We found that neutrophils control E. faecalis infection via phagocytosis, ROS production, and degranulation of azurophilic granules, but it does not trigger neutrophil extracellular trap formation (NETosis). However, E. faecalis attenuates Staphylococcus aureus-induced NETosis in polymicrobial infection by interfering with citrullination of histone, suggesting E. faecalis can actively suppress NETosis in neutrophils. Residual S. aureus-induced NETs that remain during co-infection do not impact E. faecalis, further suggesting that E. faecalis possess mechanisms to evade or survive NET-associated killing mechanisms. E. faecalis-driven reduction of NETosis corresponds with higher S. aureus survival, indicating that this immunomodulating effect could be a risk factor in promoting the virulence polymicrobial infection. These findings highlight the complexity of the immune response to polymicrobial infections and suggest that attenuated pathogen-specific immune responses contribute to pathogenesis in the mammalian host.