Virulence Determinants Are Required for Brain Abscess Formation Through Staphylococcus aureus Infection and Are Potential Targets of Antivirulence Factor Therapy

Bacterial brain abscesses (BAs) are difficult to treat with conventional antibiotics. Thus, the development of alternative therapeutic strategies for BAs is of high priority. Identifying the virulence determinants that contribute to BA formation induced by would improve the effectiveness of interven...

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Published inFrontiers in microbiology Vol. 10; p. 682
Main Authors Zheng, Ying, Shang, Weilong, Peng, Huagang, Rao, Yifan, Zhao, Xia, Hu, Zhen, Yang, Yi, Hu, Qiwen, Tan, Li, Xiong, Kun, Li, Shu, Zhu, Junmin, Hu, Xiaomei, Zhou, Renjie, Li, Ming, Rao, Xiancai
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 2019
Subjects
antivirulence factor therapy
bacteremia
brain abscess
ear colonization
Microbiology
Staphylococcus aureus
virulence determinant
brain abscess
ear colonization
Staphylococcus aureus
antivirulence factor therapy
virulence determinant
bacteremia
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Summary:Bacterial brain abscesses (BAs) are difficult to treat with conventional antibiotics. Thus, the development of alternative therapeutic strategies for BAs is of high priority. Identifying the virulence determinants that contribute to BA formation induced by would improve the effectiveness of interventions for this disease. In this study, RT-qPCR was performed to compare the expression levels of 42 putative virulence determinants of strains Newman and XQ during murine BA formation, ear colonization, and bacteremia. The alterations in the expression levels of 23 genes were further confirmed through specific TaqMan RT-qPCR. Eleven genes that persistently upregulated expression levels during BA infection were identified, and their functions in BA formation were confirmed through isogenic mutant experiments. Bacterial loads and BA volumes in mice infected with , or deletion mutants and the / double mutant strain were lower than those in mice infected with the wild-type Newman strain. The therapeutic application of monoclonal antibodies against Hla and SpA decreased bacterial loads and BA volume in mice infected with Newman. This study provides insights into the virulence determinants that contribute to staphylococcal BA formation and a paradigm for antivirulence factor therapy against infections.
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Reviewed by: Hong Du, Soochow University, China; Baolin Sun, University of Science and Technology of China, China
This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology
Edited by: Shamala Devi Sekaran, Mahsa University, Malaysia
ISSN:1664-302X
1664-302X
DOI:10.3389/fmicb.2019.00682