Mechanisms of folate metabolism-related substances affecting Staphylococcus aureus infection

Jin, Qiyuan; Xie, Xiulan; Zhai, Yaxuan; Zhang, Haifang

doi:10.1016/j.ijmm.2023.151577

Cited by 9 publications

(3 citation statements)

References 49 publications

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“…Last but not least, folate based OCM was induced in both stress conditions, and tetrahydrofolate (THF) accumulation was expected based on the enzyme expression pattern. THF was found to directly participate in crucial metabolic activities including the synthesis of nucleotide, purine and amino acids [26]. Besides, in E. coli, the overexpression of 5-formyltetrahydrofolate cyclo-ligase (Q2FZJ6 in S. aureus) promotes persister formation upon ampicillin and ofloxacin exposure [27].…”

Section: Central Carbon Metabolismmentioning

confidence: 99%

Molecular physiological characterization of the dynamics of persister formation inStaphylococcus aureus

Liu,

Huang,

Jensen

et al. 2023

Preprint

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Bacteria possess the ability to enter a growth arrested state known as persistence in order to survive antibiotic exposure. Clinically, persisters are regarded as the main causative agents for chronic and recurrent infectious diseases. To combat this antibiotic-tolerant population, a better understanding of the molecular physiology of persisters is required. In this study, we collected samples at different stages of the biphasic kill curve to reveal the dynamics of the cellular molecular changes that occur in the process of persister formation. After exposure to antibiotics with different modes of action, namely vancomycin and enrofloxacin, similar persister levels were obtained. Both shared and distinct stress responses were enriched for the respective persister populations. However, the dynamics of the presence of proteins linked to the persister phenotype throughout the biphasic kill curve and the molecular profiles in a stable persistent population did show large differences depending on the antibiotic used. This suggests that persisters at the molecular level are highly stress specific, emphasizing the importance of characterizing persisters generated under different stress conditions. Additionally, although generated persisters exhibited cross-tolerance toward tested antibiotics, combined therapies were demonstrated to be a promising approach to reduce persister levels. In conclusion, this investigation sheds light on the stress-specific nature of persisters, highlighting the necessity of tailored treatment approaches and the potential of combined therapy. Importance: By monitoring proteome and metabolites during Staphylococcus aureus persister formation under vancomycin and enrofloxacin exposure, we revealed the dynamic information of the molecular physiology of persister formation upon exposure to two different antibiotics with different modes of action. The data shows that cells that phenotypically are similarly classified as persisters, do have several molecular characteristics in common but, remarkably so, differ substantially in a significant number of other aspects of their molecular makeup. These contrasts provided valuable insights into persister eradication, which holds considerable clinical relevance.

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Section: Central Carbon Metabolismmentioning

confidence: 99%

Molecular physiological characterization of the dynamics of persister formation inStaphylococcus aureus

Liu,

Huang,

Jensen

et al. 2023

Preprint

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“…This microorganism is commonly present in the bacterial flora of the skin, oral cavity, and upper respiratory tract, serving as a primary culprit for bacterial infections in humans. [1] The spectrum of diseases caused by S. aureus spans from skin infections to potentially fatal necrotizing pneumonia. The major concern associated with this pathogen lies in its propensity to develop resistance to antibiotics.…”

Section: Introductionmentioning

confidence: 99%

Porphyrin−BODIPY Dyad: Enhancing Photodynamic Inactivation via Antenna Effect

Pérez,

Durantini,

Martínez

et al. 2024

ChemBioChem

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A porphyrin‐BODIPY dyad (P‐BDP) was obtained through covalent bonding, featuring a two‐segment design comprising a light‐harvesting antenna system connected to an energy acceptor unit. The absorption spectrum of P‐BDP resulted from an overlap of the individual spectra of its constituent parts, with the fluorescence emission of the BODIPY unit experiencing significant quenching (96%) due to the presence of the porphyrin unit. Spectroscopic, computational, and redox investigations revealed a competition between photoinduced energy and electron transfer processes. The dyad demonstrated the capability to sensitize both singlet molecular oxygen and superoxide radical anions. Additionally, P‐BDP effectively induced the photooxidation of L‐tryptophan. In suspensions of Staphylococcus aureus cells, the dyad led to a reduction of over 3.5 log (99.99%) in cell survival following 30 min of irradiation with green light. Photodynamic inactivation caused by P‐BDP was also extended to the individual bacterium level, focusing on bacterial cells adhered to a surface. This dyad successfully achieved the total elimination of the bacteria upon 20 min of irradiation. Therefore, P‐BDP presents an interesting photosensitizing structure that takes advantage of the light‐harvesting antenna properties of the BODIPY unit combined with porphyrin, offering potential to enhance photoinactivation of bacteria.

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“…Targeting vitamin metabolism pathways offers a unique opportunity to disrupt bacterial physiology and provide new avenues for antibiotic development. Some vitamins biosynthesis pathways have been exploited such as the folate (vitamin B9) synthesis (45)(46)(47); riboflavin (vitamin B2) (48)(49)(50); thiamine (vitamin B1) (51)(52)(53)(54) and biotin (vitamin B7) (55)(56)(57). Proving that vitamin metabolism is a good approach for the development of innovative antibiotics.…”

Section: Strategies For Novel Antibiotics' Randdmentioning

confidence: 99%

Structure, function, and dynamics of vitamin B6 biosynthesis enzymes from >i<Staphylococcus aureus>/i<

Barra

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Reflecting on the way here, the experiences lead me to immense personal and professional development. Besides, I will be always thankful for all the friendships that arise along the way.First, I would like to profoundly thank my parents, Abraham and Lucília, who always supported my dreams, loved me unconditionally and held me in every fall, keeping me on track.They worked hard to give me the best education, and I will be forever grateful to have them as my first mentors. I thank my advisor, Prof. Dr. Alessandro Silva Nascimento, for believing in my professional capacity and for this opportunity. The knowledge I have gained through our interactions over the years is immeasurable. In addition, I want to acknowledge the funding agencies CAPES, CNPq and FAPESP for their financial support. This study was financed by

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Mechanisms of folate metabolism-related substances affecting Staphylococcus aureus infection

Cited by 9 publications

References 49 publications

Molecular physiological characterization of the dynamics of persister formation inStaphylococcus aureus

Molecular physiological characterization of the dynamics of persister formation inStaphylococcus aureus

Porphyrin−BODIPY Dyad: Enhancing Photodynamic Inactivation via Antenna Effect

Structure, function, and dynamics of vitamin B6 biosynthesis enzymes from >i<Staphylococcus aureus>/i<

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