Key role of quorum‐sensing mutations in the development of Staphylococcus aureus clinical device‐associated infection

• Published in: Clinical and translational medicine 2022-04, Vol.12 (4), p.e801-n/a
• Main Authors: He, Lei, Zhang, Feiyang, Jian, Ying, Lv, Huiying, Hamushan, Musha, Liu, Junlan, Liu, Yao, Wang, Hua, Tang, Jin, Han, Pei, Burgin, Dylan J., Dickey, Seth W., Shen, Hao, Li, Min, Otto, Michael
• Format: Article
• Language: English
• Subjects: Antibiotics; Biofilms; Cloning; Drug resistance; Humans; Letter to Editor; Mutation; Quorum Sensing - genetics; Staphylococcal Infections - genetics; Staphylococcus aureus - genetics; Staphylococcus infections; Transplants & implants
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.801

Dear Editor, In the present study, we show that the development of Staphylococcus aureus device-associated infection involves mutations in the quorum-sensing system Agr that increase biofilm formation and thereby bacterial resistance to antibiotics. Only the locus encoding the Agr (accessory gene regulator) quorum-sensing (QS) system4 showed non-synonymous substitutions in all six isolates (Figure 1E, Tables 1 and 2, Table S2), indicating that the consistently observed phenotypes of reduced hemolysis and increased biofilm formation in the secondary isolates were due to Agr dysfunctionality. TABLE 2 Numbers of non-synonymous substitutions per gene and case Gene Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Number of cases with SNP in gene agr locus 1 1 1 3 1 1 6 agrA 0 0 0 0 1 0 1 agrC 1 1 1 3 0 1 5 istA 1 1 0 0 0 0 2 xkdX 1 0 0 0 0 0 1 sdrD 2 2 0 0 0 0 2 coa 1 0 0 0 0 0 1 rnfC 3 0 0 0 0 0 1 arsR2 2 0 0 0 0 0 1 arsB 1 0 0 0 0 0 1 abgT 1 0 0 0 0 0 1 lpl 0 1 0 0 0 0 1 yhcN 0 2 0 0 0 0 1 clfB 0 1 0 1 1 0 3 cstA 0 1 0 0 0 0 1 sdrC 0 0 1 0 0 0 1 M013TW_1443 0 0 1 0 0 0 1 M013TW_1444 0 0 1 0 0 0 1 terL 0 0 1 0 0 0 1 M013TW_1441 0 0 1 0 0 0 1 M013TW_2107 0 0 1 0 0 0 1 sasG 0 0 1 0 0 0 1 arcC 0 0 0 0 0 1 1 For the analysis of antibiotic resistance exhibited by the T1 and T2 isolate pairs, we chose levofloxacin (Lev), vancomycin (Van) and clindamycin (Cli) as they are in frequent clinical use for surgical implant infections and were among the most frequently used antibiotics in our study (Table S1). [...]we selected three T2 isolates in which we repaired the detected agr mutation by an allelic replacement procedure.