AUTHOR=Yu Jinlong , Jiang Feng , Zhang Feiyang , Hamushan Musha , Du Jiafei , Mao Yanjie , Wang Qiaojie , Han Pei , Tang Jin , Shen Hao 

TITLE=Thermonucleases Contribute to Staphylococcus aureus Biofilm Formation in Implant-Associated Infections–A Redundant and Complementary Story

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.687888

DOI=10.3389/fmicb.2021.687888

ISSN=1664-302X

ABSTRACT=<p>Biofilms formed by <italic>Staphylococcus aureus</italic> are one of the predominant causes of implant-associated infections (IAIs). Previous studies have found that <italic>S. aureus</italic> nucleases <italic>nuc1</italic> and <italic>nuc2</italic> modulate biofilm formation. In this study, we found low <italic>nuc1</italic>/<italic>nuc2</italic> expression and high biofilm-forming ability among IAI isolates. Furthermore, in a mouse model of exogenous IAIs, Δ<italic>nuc1/2</italic> exhibited higher bacterial load on the surface of the implant than that exhibited by the other groups (WT, Δ<italic>nuc1</italic>, and Δ<italic>nuc2</italic>). Survival analysis of the hematogenous IAI mouse model indicated that <italic>nuc1</italic> is a virulence factor related to mortality. We then detected the influence of <italic>nuc1</italic> and <italic>nuc2</italic> on biofilm formation and immune evasion <italic>in vitro</italic>. Observation of <italic>in vitro</italic> biofilm structures with scanning electron microscopy and evaluation of bacterial aggregation with flow cytometry revealed that both <italic>nuc1</italic> and <italic>nuc2</italic> are involved in biofilm structuring and bacterial aggregation. Unlike <italic>nuc1</italic>, which is reported to participate in immune evasion, <italic>nuc2</italic> cannot degrade neutrophil extracellular traps. Moreover, we found that <italic>nuc1</italic>/<italic>nuc2</italic> transcription is negatively correlated during <italic>S. aureus</italic> growth, and a possible complementary relationship has been proposed. In conclusion, <italic>nuc1</italic>/<italic>nuc2</italic> are complementary genes involved in biofilm formation in exogenous IAIs. However, <italic>nuc2</italic> contributes less to virulence and is not involved in immune evasion.</p>