Frontiers in microbiology · 2026
Unlocking the potential of Pseudomonas aeruginosa QS intermediates as antimicrobial synergists against three multidrug-resistant enteric bacteria.
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.
Kiran Saba, Alhegaili Alaa S, Al-Dayan Noura, Naseem Zubera, Siddique Waqar, Ayoub Itra, Iqbal Shoaib, Jabeen Sobia, Habib Fazal-E, Taj Saman, Hussain Ashfaq, Bashir Rizwan, Sarwar Yasra, Ali Aamir, Rauf Waqar, Jander Georg, Iqbal Mazhar
Аннотация
INTRODUCTION: Antimicrobial resistance in the Enterobacteriaceae poses a global health concern by jeopardizing the effectiveness of antibiotics. The scarcity of new antibiotics has prompted increased interest in natural bioactive secondary metabolites derived from microbial sources and their co-action with existing antimicrobials.
METHODS: In this study, we investigated the bioactivity of crude extracts from Pseudomonas aeruginosa MC9 (accession no. MK530186) and evaluated the in-vitro antimicrobial-augmenting efficacy of its quorum sensing (QS) effectors against multidrug-resistant strains of Salmonella Typhi (S. Typhi-29C), Salmonella Typhimurium (S. Typhimurium-W20), and Escherichia coli (E. coli SS1). Mass spectrometry was used to identify secondary metabolites, and combination assays followed by growth curve analysis were performed to assess interaction effects under sub-inhibitory conditions.
RESULTS: The MC9 extract exhibited inhibition zones of 26±1.5, 24±1, and 19±1.5 mm, with minimum inhibitory concentrations of 16, 32, and 256 mg/mL against S. Typhimurium-W20, S. Typhi-29C, and E. coli-E92, respectively. Mass spectrometric analysis revealed the presence of 5-methyl-1(5H)-phenazinone (pyocyanin), rhamnolipids, 4-hydroxy-2heptylquinoline (PQS), and 2-heptyl-3-hydroxy-4(1H)-quinolone (HHQ). Notably, pyocyanin and rhamnolipids exhibited significant antimicrobial activities across a concentration range from 0.04 mg/mL to 50 mg/mL, whereas HHQ and PQS showed no anti-Enterobacteriaceae activity up to 5 mg/mL. Combination assays demonstrated that all four QS effectors potentiate the activity of conventional antibiotics. Pyocyanin showed the highest synergistic effect, with a 300% increase in the inhibition zone when combined with sulfamethoxazole/trimethoprim (23.75/1.25 µg/mL) against S. Typhimurium-W20. Rhamnolipids exhibited a 106% increase in synergy with ceftriaxone (30 μg/mL) against E. coli-SS1, whereas HHQ (10 μg/mL) showed a 257% increase with ampicillin (10 μg/mL) against E. coli-SS1. PQS displayed the highest synergistic effect of 109% with amoxicillin clavulanic acid (30 μg/mL) against E. coli-SS1. Moreover, growth curve analysis revealed a dose-dependent reduction in bacterial growth with sub-inhibitory concentrations of antimicrobials, particularly for the combinations exhibiting the highest synergy across the QS effectors.
DISCUSSION: These findings demonstrate the potential of the QS effectors in reducing the required dosage of antibiotics against resistant Enterobacteriaceae strains and highlight the need to develop a comprehensive understanding of the underlying mechanisms for the co-action of antimicrobials and QS mediators.
METHODS: In this study, we investigated the bioactivity of crude extracts from Pseudomonas aeruginosa MC9 (accession no. MK530186) and evaluated the in-vitro antimicrobial-augmenting efficacy of its quorum sensing (QS) effectors against multidrug-resistant strains of Salmonella Typhi (S. Typhi-29C), Salmonella Typhimurium (S. Typhimurium-W20), and Escherichia coli (E. coli SS1). Mass spectrometry was used to identify secondary metabolites, and combination assays followed by growth curve analysis were performed to assess interaction effects under sub-inhibitory conditions.
RESULTS: The MC9 extract exhibited inhibition zones of 26±1.5, 24±1, and 19±1.5 mm, with minimum inhibitory concentrations of 16, 32, and 256 mg/mL against S. Typhimurium-W20, S. Typhi-29C, and E. coli-E92, respectively. Mass spectrometric analysis revealed the presence of 5-methyl-1(5H)-phenazinone (pyocyanin), rhamnolipids, 4-hydroxy-2heptylquinoline (PQS), and 2-heptyl-3-hydroxy-4(1H)-quinolone (HHQ). Notably, pyocyanin and rhamnolipids exhibited significant antimicrobial activities across a concentration range from 0.04 mg/mL to 50 mg/mL, whereas HHQ and PQS showed no anti-Enterobacteriaceae activity up to 5 mg/mL. Combination assays demonstrated that all four QS effectors potentiate the activity of conventional antibiotics. Pyocyanin showed the highest synergistic effect, with a 300% increase in the inhibition zone when combined with sulfamethoxazole/trimethoprim (23.75/1.25 µg/mL) against S. Typhimurium-W20. Rhamnolipids exhibited a 106% increase in synergy with ceftriaxone (30 μg/mL) against E. coli-SS1, whereas HHQ (10 μg/mL) showed a 257% increase with ampicillin (10 μg/mL) against E. coli-SS1. PQS displayed the highest synergistic effect of 109% with amoxicillin clavulanic acid (30 μg/mL) against E. coli-SS1. Moreover, growth curve analysis revealed a dose-dependent reduction in bacterial growth with sub-inhibitory concentrations of antimicrobials, particularly for the combinations exhibiting the highest synergy across the QS effectors.
DISCUSSION: These findings demonstrate the potential of the QS effectors in reducing the required dosage of antibiotics against resistant Enterobacteriaceae strains and highlight the need to develop a comprehensive understanding of the underlying mechanisms for the co-action of antimicrobials and QS mediators.