Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2026
Nationwide dalbavancin surveillance identifies sagB-associated cell-wall adaptation linked to reduced lipoglycopeptide susceptibility in CC5 Staphylococcus aureus.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Hong Yueqin, Zhuang Hemu, Wang Haiping, Guo Yan, Shi Keren, Chen Yiyi, Zhu Feiteng, Zhang Xin, Hu Fupin, Sun Lu, Yu Yunsong, Chen Yan
Аннотация
AIMS: Dalbavancin is a long-acting lipoglycopeptide with potent activity against Staphylococcus aureus. However, the emergence of reduced dalbavancin susceptibility and its underlying molecular mechanisms remain poorly understood.
METHODS: Dalbavancin MICs were determined for 1803 S. aureus isolates from 37 hospitals in 27 provinces of China. Comparative genomics of a clinical dalbavancin-nonsusceptible (DAL-NS) isolate and in vitro vancomycin-selected derivatives was performed to identify resistance-associated mutations. The role of sagB was assessed by gene deletion and complementation, followed by antimicrobial susceptibility testing and phenotypic assays. Transcriptomic profiling, autolysis assays, electron microscopy, cytochrome c binding assays, and time-kill assays were performed to characterize the cellular effects of sagB dysfunction.
RESULTS: Dalbavancin showed potent activity, with MIC50/MIC90 values of 0.06/0.125 μg/mL, and only one nonsusceptible isolate was detected (0.06%, 1/1803). This isolate belonged to ST5523/CC5 and had prior vancomycin exposure but no dalbavancin treatment. sagB mutations occurred in both the clinical isolate and independent vancomycin-selected derivatives with reduced dalbavancin susceptibility. Genetic complementation and deletion supported sagB dysfunction as contributing to reduced susceptibility to lipoglycopeptides, glycopeptides, and lipopeptides, with reciprocal β-lactam sensitization. Mechanistically, sagB dysfunction altered cell-wall hydrolase expression, autolysis, and envelope properties, and was associated with prolonged survival under dalbavancin exposure but enhanced killing by oxacillin.
CONCLUSIONS: Dalbavancin remains highly active against clinical S. aureus in China. Rare nonsusceptibility may emerge under glycopeptide pressure through lineage-conditioned sagB-associated cell-wall remodeling.
METHODS: Dalbavancin MICs were determined for 1803 S. aureus isolates from 37 hospitals in 27 provinces of China. Comparative genomics of a clinical dalbavancin-nonsusceptible (DAL-NS) isolate and in vitro vancomycin-selected derivatives was performed to identify resistance-associated mutations. The role of sagB was assessed by gene deletion and complementation, followed by antimicrobial susceptibility testing and phenotypic assays. Transcriptomic profiling, autolysis assays, electron microscopy, cytochrome c binding assays, and time-kill assays were performed to characterize the cellular effects of sagB dysfunction.
RESULTS: Dalbavancin showed potent activity, with MIC50/MIC90 values of 0.06/0.125 μg/mL, and only one nonsusceptible isolate was detected (0.06%, 1/1803). This isolate belonged to ST5523/CC5 and had prior vancomycin exposure but no dalbavancin treatment. sagB mutations occurred in both the clinical isolate and independent vancomycin-selected derivatives with reduced dalbavancin susceptibility. Genetic complementation and deletion supported sagB dysfunction as contributing to reduced susceptibility to lipoglycopeptides, glycopeptides, and lipopeptides, with reciprocal β-lactam sensitization. Mechanistically, sagB dysfunction altered cell-wall hydrolase expression, autolysis, and envelope properties, and was associated with prolonged survival under dalbavancin exposure but enhanced killing by oxacillin.
CONCLUSIONS: Dalbavancin remains highly active against clinical S. aureus in China. Rare nonsusceptibility may emerge under glycopeptide pressure through lineage-conditioned sagB-associated cell-wall remodeling.