<i>ldhA</i>‐induced persister in <i>Escherichia coli</i> is formed through accidental SOS response via intracellular metabolic perturbation

Yamamoto, Naoki; Ohno, Yurino; Tsuneda, Satoshi

doi:10.1111/1348-0421.12970

Cited by 3 publications

(1 citation statement)

References 52 publications

(104 reference statements)

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“…However, a notable downside of using antioxidants is that this could result in concomitantly lower beneficial ROS‐mediated mechanisms of the immune system (Dumas & Knaus, 2021), leading to increased infections and longer infection durations. Preventing active persistence mechanisms by decreasing active stress responses such as the SOS response using RecA inhibitors (Alam et al , 2016; Yamamoto et al , 2022), the general stress response using mesalamine (Dahl et al , 2017) or the stringent response by limiting ppGpp production (Nguyen et al , 2011; Dutta et al , 2019) has also been associated with lower persister levels and an improved treatment in animal infection models. Another strategy to decrease the number of persisters in a population is by resensitizing them to antibiotics by inducing their regrowth.…”

Section: Introductionmentioning

confidence: 99%

Environmental, mechanistic and evolutionary landscape of antibiotic persistence

et al. 2023

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Recalcitrant infections pose a serious challenge by prolonging antibiotic therapies and contributing to the spread of antibiotic resistance, thereby threatening the successful treatment of bacterial infections. One potential contributing factor in persistent infections is antibiotic persistence, which involves the survival of transiently tolerant subpopulations of bacteria. This review summarizes the current understanding of antibiotic persistence, including its clinical significance and the environmental and evolutionary factors at play. Additionally, we discuss the emerging concept of persister regrowth and potential strategies to combat persister cells. Recent advances highlight the multifaceted nature of persistence, which is controlled by deterministic and stochastic elements and shaped by genetic and environmental factors. To translate in vitro findings to in vivo settings, it is crucial to include the heterogeneity and complexity of bacterial populations in natural environments. As researchers continue to gain a more holistic understanding of this phenomenon and develop effective treatments for persistent bacterial infections, the study of antibiotic persistence is likely to become increasingly complex.

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Section: Introductionmentioning

confidence: 99%

Environmental, mechanistic and evolutionary landscape of antibiotic persistence

et al. 2023

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Novel Insights into the Antimicrobial and Antibiofilm Activity of Pyrroloquinoline Quinone (PQQ); In Vitro, In Silico, and Shotgun Proteomic Studies

Labib,

Alqahtani,

Abo Nahas

et al. 2024

Biomolecules

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Microbial infections pose a significant global health threat, affecting millions of individuals and leading to substantial mortality rates. The increasing resistance of microorganisms to conventional treatments requires the development of novel antimicrobial agents. Pyrroloquinoline quinone (PQQ), a natural medicinal drug involved in various cellular processes, holds promise as a potential antimicrobial agent. In the present study, our aim was, for the first time, to explore the antimicrobial activity of PQQ against 29 pathogenic microbes, including 13 fungal strains, 8 Gram-positive bacteria, and 8 Gram-negative bacteria. Our findings revealed potent antifungal properties of PQQ, particularly against Syncephalastrum racemosum, Talaromyces marneffei, Candida lipolytica, and Trichophyton rubrum. The MIC values varied between fungal strains, and T. marneffei exhibited a lower MIC, indicating a greater susceptibility to PQQ. In addition, PQQ exhibited notable antibacterial activity against Gram-positive and -negative bacteria, with a prominent inhibition observed against Staphylococcus epidermidis, Proteus vulgaris, and MRSA strains. Remarkably, PQQ demonstrated considerable biofilm inhibition against the MRSA, S. epidermidis, and P. vulgaris strains. Transmission electron microscopy (TEM) studies revealed that PQQ caused structural damage and disrupted cell metabolism in bacterial cells, leading to aberrant morphology, compromised cell membrane integrity, and leakage of cytoplasmic contents. These findings were further affirmed by shotgun proteomic analysis, which revealed that PQQ targets several important cellular processes in bacteria, including membrane proteins, ATP metabolic processes, DNA repair processes, metal-binding proteins, and stress response. Finally, detailed molecular modeling investigations indicated that PQQ exhibits a substantial binding affinity score for key microbial targets, including the mannoprotein Mp1P, the transcriptional regulator TcaR, and the endonuclease PvuRTs1I. Taken together, our study underscores the effectiveness of PQQ as a broad-spectrum antimicrobial agent capable of combating pathogenic fungi and bacteria, while also inhibiting biofilm formation and targeting several critical biological processes, making it a promising therapeutic option for biofilm-related infections.

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Characterization of Escherichia coli Persisters from Biofilm Culture: Multiple Dormancy Levels and Multigenerational Memory in Formation

Ikeda,

Maeda

2024

Microorganisms

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Persister cells (PCs), a subpopulation occurring within normal cells, exhibit a transient tolerance to antibiotics because of their dormant state. PCs are categorized into two types: type I PCs, which emerge during the stationary phase, and type II PCs, which emerge during the logarithmic phase. Using the conventional colony-forming method, we previously demonstrated that type I PCs of Escherichia coli form more frequently in air–solid biofilm culture than in liquid culture. In the current study, we modified a cell filamentation method as a more efficient and rapid alternative for quantifying PCs. This modified method yielded results consistent with those of the conventional method with 103–104 times higher sensitivity and less detection time, within several hours, and further revealed the existence of multiple levels of type I PCs, including a substantial number of deeply dormant cells. This study also discovered a potential epigenetic memory mechanism, spanning several generations (four or six cell divisions), which influences type II PC formation based on prior biofilm experience in E. coli.

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ldhA‐induced persister in Escherichia coli is formed through accidental SOS response via intracellular metabolic perturbation

Cited by 3 publications

References 52 publications

Environmental, mechanistic and evolutionary landscape of antibiotic persistence

Environmental, mechanistic and evolutionary landscape of antibiotic persistence

Novel Insights into the Antimicrobial and Antibiofilm Activity of Pyrroloquinoline Quinone (PQQ); In Vitro, In Silico, and Shotgun Proteomic Studies

Characterization of Escherichia coli Persisters from Biofilm Culture: Multiple Dormancy Levels and Multigenerational Memory in Formation

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