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Researchers used transposon insertion sequencing in Escherichia coli to identify genes affecting susceptibility to streptomycin, an important aminoglycoside antibiotic. The study uncovered both known and novel genes that influence susceptibility when disrupted, including those involved in respiration, protein export, and cell division, while also revealing that the inner membrane transporter SbmA contributes to aminoglycoside uptake. Contrary to common assumptions, many susceptible mutants did not show the expected inner membrane hyperpolarization, refining current models of how aminoglycosides interact with bacterial cells.
Why it matters
These findings advance understanding of aminoglycoside mechanisms in Gram-negative bacteria, which is crucial given their clinical importance and the incomplete knowledge of their uptake pathways. The identification of SbmA and other genes involved in streptomycin susceptibility could inform the development of adjuvant therapies that enhance antibiotic effectiveness and help combat antimicrobial resistance.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Aminoglycosides are critical antibiotics with partially elucidated mechanisms of uptake and action in Gram-negative bacteria. Importantly, although energy-dependent uptake across the inner membrane has been well-established, the specific molecular mechanisms involved have not been definitively identified. To deepen understanding of genetic factors influencing susceptibility and resistance to streptomycin, we applied transposon insertion sequencing in Escherichia coli K-12. This approach identified both known and novel genes whose disruption increased susceptibility, including those involved in respiration, protein export, cell division, and uncharacterised functions. Notably, voltage-sensitive membrane dye-based assays revealed that many susceptible mutants did not display inner membrane hyperpolarisation as often assumed. Conversely, disruption of certain genes, such as the inner membrane antimicrobial peptide transporter SbmA, conferred low-level resistance, with sbmA overexpression increasing streptomycin sensitivity, suggesting its role in aminoglycoside uptake. These findings refine the model of aminoglycoside interaction with various pathways and highlight potential targets for adjuvant therapies to combat antimicrobial resistance.