First description of rpsJ and mepA mutations associated with tigecycline resistance in Staphylococcus aureus isolated from a cystic fibrosis patient during antibiotic therapy

Eravacycline susceptibility was impacted by genetic mutation of 30S ribosome subunits, and branched-chain amino acid transport system II carrier protein, Na/Pi cotransporter family protein in Staphylococcus aureus

“…Recent crystallographic analysis studies have revealed the same mechanism of the new-generation tetracycline class antibiotics, including Tige, Omada and Erava, to inhibit bacterial protein synthesis by binding to the 30S ribosomal subunits, including 16SrRNA and 30S ribosome protein S10 [8,18]. Previous researches indicated that genetic mutations affecting the 30S ribosome subunits (i.e., 16SrRNA and ribosome proteins S10) have been shown to confer resistance to Tige and Omada in S. aureus [9][10][11][12][13][14][15][16][17]18]. However, the characteristics of genetic mutation of the 30S ribosome subunits and cross resistance in Erava resistant S. aureus remains unknown.…”

“…Meanwhile, our study revealed high frequency of genetic mutations in 30S ribosome protein S10 in Erava-derived resistant isolates, indicating this protein might be an important factor in Erava resistance evolution. Previous multiple reports have shown that the mutation in 30S ribosome protein S10 of S. aureus can result in the MIC elevation of tetracycline, Omada and Tige, indicating its important role in the resistance evolution of tetracycline class drugs [6,9,12,13,15,17]. Therefore, the cross resistance under Erava pressure with Omada and Tige might be mainly explained by the genetic mutation of 30S ribosome subunits The frequent occurrence of antibiotics heteroresistance can result in the treatment failure.…”

“…Our previous data indicated that tet(K) was frequently detected in MSSA with Erava MIC ≥0.5mg/L and it's still unknown whether tet(K) participated in the Erava heteroresistance or resistance [7]. The reduced susceptibility to Tige have been widely explained by the emergent mutations in genes encoding several 30S ribosome subunits, including 16S rRNA and 30S ribosome protein S10 [8][9][10][11][12][13][14][15][16][17]. The clinical significance of the genetic mutations of 30S ribosome subunits remains elusive should be further studied.…”

Eravacycline activity against clinical S. aureus isolates from China: in vitro activity, MLST profiles and heteroresistance

“…Upregulation of MepA, a multidrug-resistant efflux pump, has been shown to confer tigecycline resistance in S. aureus [ 16 – 18 ]. Furthermore, in strain SA984 S. aureus , the erava MIC increased from 0.004 mg/L in a MepA-negative parent isolate to 0.016 mg/L in S. aureus expressing MepA, whereas MepA addition increased tigecycline MICs from 0.016 mg/L to 1.0 mg/L, pointing to a negligible effect of MepA on erava resistance relative to its effect on tigecycline resistance [ 3 , 8 , 16 ].…”

Eravacycline susceptibility was impacted by genetic mutation of 30S ribosome subunits, and branched-chain amino acid transport system II carrier protein, Na/Pi cotransporter family protein in Staphylococcus aureus

“…Our previous data indicated that tet(K) was frequently detected in MSSA with Erava MIC ≥ 0.5 mg/L and it's still unknown whether tet(K) participated in the Erava heteroresistance or resistance [7]. The reduced susceptibility to Tige have been widely explained by the emergent mutations in genes encoding several 30S ribosome subunits, including 16S rRNA and 30S ribosome protein S10 [8][9][10][11][12][13][14][15][16][17]. The clinical significance of the genetic mutations of 30S ribosome subunits remains elusive should be further studied.…”