Fast identification of off‐target liabilities in early antibiotic discovery with Fourier‐transform infrared spectroscopy

Cunha, Bernardo Ribeiro da; Aleixo, Sandra M.; Fonseca, Luís P.; Calado, Cecı́lia R.C.

doi:10.1002/bit.27915

Cited by 5 publications

(2 citation statements)

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“…Due to the high sensitivity and specificity of FTIR spectroscopy when capturing the bacteria’s molecular fingerprint, the technique has also been used to evaluate the impact of drugs on the bacteria’s metabolism [ 25 , 26 , 27 ]. According to this, in the present work, the technique was applied to evaluate the impact of EGCG on the MSSA and MRSA strains.…”

Section: Resultsmentioning

confidence: 99%

Epigenetic and Drug Response Modulation of Epigalocaten-In-3-Gallate in Staphylococcus aureus with Divergent Resistance Phenotypes

et al. 2023

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Healthcare-associated methicillin-resistant Staphylococcus aureus infections represent extremely high morbidity and mortality rates worldwide. We aimed to assess the antimicrobial potential and synergistic effect between Epigalocatenin-3-gallate (EGCG) and different antibiotics in S. aureus strains with divergent resistance phenotypes. EGCG exposure effects in epigenetic and drug resistance key modulators were also evaluated. S. aureus strains (n = 32) were isolated from infected patients in a Lisbon hospital. The identification of the S. aureus resistance phenotype was performed through automatized methods. The antibiotic synergistic assay was performed through disk diffusion according to EUCAST guidelines with co-exposure to EGCG (250, 100, 50 and 25 µg/mL). The bacteria’s molecular profile was assessed through FTIR spectroscopy. The transcriptional expression of OrfX, SpdC and WalKR was performed by using qRT-PCR. FTIR-spectroscopy analysis enabled the clear discrimination of MRSA/MSSA strains and the EGCG exposure effect in the bacteria’s molecular profiles. Divergent resistant phenotypes were associated with divergent transcriptional expression of the epigenetic modulator OrfX, particularly in MRSA strains, as well as the key drug response modulators SpdC and WalKR. These results clearly demonstrate that EGCG exposure alters the expression patterns of key epigenetic and drug response genes with associated divergent-resistant profiles, which supports its potential for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms.

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Section: Resultsmentioning

confidence: 99%

Epigenetic and Drug Response Modulation of Epigalocaten-In-3-Gallate in Staphylococcus aureus with Divergent Resistance Phenotypes

et al. 2023

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“…Further combination of FTIR spectroscopy data with ML-based spectral processing led to increased discrimination accuracy [ 45 ]. This approach was further applied to predict MoA and off-target liabilities of antibiotics [ 46 ]. FTIR spectra provide molecular insight into most biologically relevant molecules; therefore, FTIR-based methods are a very promising tool in antibiotic development.…”

Section: Sensing the Antibiotic Mechanism Of Actionmentioning

confidence: 99%

Sensing of Antibiotic–Bacteria Interactions

Baranova,

Tyurin,

Korshun

et al. 2023

Antibiotics

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Sensing of antibiotic–bacteria interactions is an important area of research that has gained significant attention in recent years. Antibiotic resistance is a major public health concern, and it is essential to develop new strategies for detecting and monitoring bacterial responses to antibiotics in order to maintain effective antibiotic development and antibacterial treatment. This review summarizes recent advances in sensing strategies for antibiotic–bacteria interactions, which are divided into two main parts: studies on the mechanism of action for sensitive bacteria and interrogation of the defense mechanisms for resistant ones. In conclusion, this review provides an overview of the present research landscape concerning antibiotic–bacteria interactions, emphasizing the potential for method adaptation and the integration of machine learning techniques in data analysis, which could potentially lead to a transformative impact on mechanistic studies within the field.

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