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

• Published in: Frontiers in microbiology Vol. 12; p. 687888
• Main Authors: Yu, Jinlong, Jiang, Feng, Zhang, Feiyang, Hamushan, Musha, Du, Jiafei, Mao, Yanjie, Wang, Qiaojie, Han, Pei, Tang, Jin, Shen, Hao
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 24-06-2021
• Subjects: biofilm; implant associated infections; Microbiology; periprosthetic joint infection; Staphylococcus aureus; thermonuclease
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2021.687888

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