Small regulatory RNA Teg58 enhances biofilm-mediated chronic infection in healthcare-associated Staphylococcus aureus
摘要
Staphylococcus aureus (S. aureus) is a clinically infamous pathogen causing metastatic or complicated infections. Healthcare-associated S. aureus (HA-SA), represented by the ST5 clonotype, dominates S. aureus infections in China. Small RNAs (sRNAs), such as RNAIII, play important roles in regulating S. aureus virulence; however, their specific regulatory functions in chronic infections—particularly in ST5 HA-SA isolates—remain incompletely understood. By comparing the transcriptomes of ST5 HA-SA with those of representative community-associated S. aureus (CA-SA) ST398 clonotype strains, we identified a highly transcribed sRNA, Teg58, in ST5 HA-SA strains. Rapid amplification of cDNA ends (RACE) and Northern blot analysis confirmed that Teg58 is approximately 369 nucleotides in length and located between ecb and sa1001, partially overlapping with the 3’ end of sa1001. Teg58 enhances resistance to neutrophil phagocytosis in ST5 HA-SA by interacting with sa1001 mRNA, thereby promoting its stability and translation. Transcriptome analysis and target prediction revealed that Teg58 binds to isaA mRNA and promotes its translation. Through this mechanism, Teg58 positively regulates biofilm formation, facilitating nasal colonization and in vivo biofilm-associated subcutaneous infection in ST5 HA-SA. Collectively, these findings identify Teg58 as an important regulatory factor that promotes chronic infection in HA-SA strains.