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1.
EBioMedicine ; 102: 105041, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38484555

RESUMEN

BACKGROUND: Chemoresistance is a critical factor contributing to poor prognosis in clinical patients with cancer undergoing postoperative adjuvant chemotherapy. The role of gut microbiota in mediating resistance to tumour chemotherapy remains to be investigated. METHODS: Patients with CRC were categorised into clinical benefit responders (CBR) and no clinical benefit responders (NCB) based on chemotherapy efficacy. Differential bacterial analysis using 16S rRNA sequencing revealed Desulfovibrio as a distinct microbe between the two groups. Employing a syngeneic transplantation model, we assessed the effect of Desulfovibrio on chemotherapy by measuring tumour burden, weight, and Ki-67 expression. We further explored the mechanisms underlying the compromised chemotherapeutic efficacy of Desulfovibrio using metabolomics, western blotting, colony formation, and cell apoptosis assays. FINDINGS: In comparison, Desulfovibrio was more abundant in the NCB group. In vivo experiments revealed that Desulfovibrio colonisation in the gut weakened the efficacy of FOLFOX. Treatment with Desulfovibrio desulfuricans elevates serum S-adenosylmethionine (SAM) levels. Interestingly, SAM reduced the sensitivity of CRC cells to FOLFOX, thereby promoting the growth of CRC tumours. These experiments suggest that SAM promotes the growth and metastasis of CRC by driving the expression of methyltransferase-like 3 (METTL3). INTERPRETATION: A high abundance of Desulfovibrio in the intestines indicates poor therapeutic outcomes for postoperative neoadjuvant FOLFOX chemotherapy in CRC. Desulfovibrio drives the manifestation of METTL3 in CRC, promoting resistance to FOLFOX chemotherapy by increasing the concentration of SAM. FUNDING: This study is supported by Wuxi City Social Development Science and Technology Demonstration Project (N20201005).


Asunto(s)
Neoplasias Colorrectales , Desulfovibrio desulfuricans , Humanos , Apoptosis , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Desulfovibrio desulfuricans/genética , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Metiltransferasas , ARN Ribosómico 16S/genética , Leucovorina , Compuestos Organoplatinos , Protocolos de Quimioterapia Combinada Antineoplásica
6.
J Hazard Mater ; 459: 132146, 2023 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-37499495

RESUMEN

This paper describes a unique molecular mechanism for the EPS-mediated synthesis of CdS QDs by sulfate-reducing bacteria (SRB) under carbon source-induced reinforcement. Under the induced by carbon sources (HCOONa, CH3COONa and C6H12O6), there was a significant increase in EPS production of SRB, particularly in protein, and the capacity of Cd(II) adsorption was further enhanced. CdS QDs were extracellularly synthesized by adding S2- after Cd(II) adsorption. The results showed that CdS QDs were wrapped or adhered by EPS, and the most significant increase in Arg and Lys among basic amino acids in EPS after HCOONa-induced was 133.34% and 63.89%, respectively. This may serve as a biological template for QD synthesis, producing protein gels with a large number of microcavities and controlling the nucleation of CdS QDs. The highest yield of HCOONa-CdS was achieved after induction, with 23.59 g/g biomass per unit strain, which was 447.34% higher than that before induction and was at a high level in previous studies. The synthesized CdS QDs were uniform in size distribution and had higher luminescence activity and a larger specific surface area than those synthesized by the chemical synthesis route, provides a new idea for EPS treatment of heavy metal wastewater and metal biorecovery.


Asunto(s)
Desulfovibrio desulfuricans , Desulfovibrio , Metales Pesados , Cadmio/metabolismo , Desulfovibrio desulfuricans/metabolismo , Carbono/metabolismo , Metales Pesados/metabolismo
7.
Emerg Infect Dis ; 29(8): 1680-1681, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37486321

RESUMEN

An 84-year-old man in Japan who had undergone endovascular aortic repair 9 years earlier had an infected aneurysm develop. We detected Desulfovibrio desulfuricans MB at the site. The patient recovered after surgical debridement, artificial vessel replacement, and appropriate antimicrobial therapy. Clinicians should suspect Desulfovibrio spp. infection in similar cases.


Asunto(s)
Aneurisma , Desulfovibrio desulfuricans , Masculino , Humanos , Anciano de 80 o más Años , Japón
8.
Bioelectrochemistry ; 153: 108469, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37235890

RESUMEN

Effect of exogenous riboflavin on sulfate-reducing bacteria (SRB) corrosion of a spirally welded joint (WJ) of X80 steel was investigated by SEM/EDS, XPS, 3D ultra-depth microscopy and electrochemical measurements. The main style of SRB corrosion of the WJ is local corrosion. The local corrosion sensitivity of the heating affected zone (HAZ) of the WJ was always lower than that of the weld zone (WZ) and base metal (BM) in all the SRB-inoculated mediums. SRB corrosion of the WJ is selective. With the dosage increase of riboflavin, the selective pitting corrosion of the WJ becomes more pronounced.


Asunto(s)
Desulfovibrio desulfuricans , Desulfovibrio , Biopelículas , Corrosión , Acero , Riboflavina
9.
N Biotechnol ; 72: 128-138, 2022 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-36396027

RESUMEN

A range of Desulfovibrio spp. can reduce metal ions to form metallic nanoparticles that remain attached to their surfaces. The bioreduction of palladium (Pd) has been given considerable attention due to its extensive use in areas of catalysis and electronics and other technological domains. In this study we report, for the first time, evidence for Pd(II) reduction by the highly corrosive Desulfovibrio ferrophilus IS5 strain to form surface attached Pd nanoparticles, as well as rapid formation of Pd(0) coated microbial nanowires. These filaments reached up to 8 µm in length and led to the formation of a tightly bound group of interconnected cells with enhanced ability to attach to a low carbon steel surface. Moreover, when supplied with high concentrations of Pd (≥ 100 mmol Pd(II) g-1 dry cells), both Desulfovibrio desulfuricans and D. ferrophilus IS5 formed bacteria/Pd hybrid porous microstructures comprising millions of cells. These three-dimensional structures reached up to 3 mm in diameter with a dose of 1200 mmol Pd(II) g-1 dry cells. Under suitable hydrodynamic conditions during reduction, two-dimensional nanosheets of Pd metal were formed that were up to several cm in length. Lower dosing of Pd(II) for promoting rapid synthesis of metal coated nanowires and enhanced attachment of cells onto metal surfaces could improve the efficiency of various biotechnological applications such as microbial fuel cells. Formation of biologically stimulated Pd microstructures could lead to a novel way to produce metal scaffolds or nanosheets for a wide variety of applications.


Asunto(s)
Desulfovibrio desulfuricans , Desulfovibrio , Paladio/química , Paladio/metabolismo , Desulfovibrio desulfuricans/metabolismo , Desulfovibrio/metabolismo , Catálisis
10.
Rev Argent Microbiol ; 54(4): 314-317, 2022.
Artículo en Español | MEDLINE | ID: mdl-35688718

RESUMEN

Desulfovibrio spp. are strict anaerobes that are ubiquitous in nature. They can reside in the human or animal gastrointestinal tract and, as they are also environmental bacteria, may be present in soil and water. They can persist asymptomatically in the intestine or behave as opportunistic pathogens associated with primary bacteremia and intraabdominal infections. Several Desulfovibrio spp. infections may be underestimated due to their slow growth rate and because many laboratories do not routinely perform anaerobic cultures. Simple tests such as motility detection on a fresh subculture, Gram stain to confirm cell morphology, presence of H2S in SIM agar and production of a red fluorescence in alkaline pH under UV light would be indicative of Desulfovibrio spp. Here we report the case of Desulfovibrio desulfuricans bacteremia in a woman with clinical picture of abdominal sepsis due to gangrenous appendicitis with multiple organ failure.


Asunto(s)
Bacteriemia , Desulfovibrio desulfuricans , Infecciones Intraabdominales , Femenino , Humanos , Bacteriemia/microbiología
11.
Appl Environ Microbiol ; 88(12): e0058022, 2022 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-35638843

RESUMEN

The growth of sulfate-reducing bacteria (SRB) and associated hydrogen sulfide production can be problematic in a range of industries such that inhibition strategies are needed. A range of SRB can reduce metal ions, a strategy that has been utilized for bioremediation, metal recovery, and synthesis of precious metal catalysts. In some instances, the metal remains bound to the cell surface, and the impact of this coating on bacterial cell division and metabolism has not previously been reported. In this study, Desulfovibrio desulfuricans cells (1g dry weight) enabled the reduction of up to 1500 mmol (157.5 g) palladium (Pd) ions, resulting in cells being coated in approximately 1 µm of metal. Thickly coated cells were no longer able to metabolize or divide, ultimately leading to the death of the population. Increasing Pd coating led to prolonged inhibition of sulfate reduction, which ceased completely after cells had been coated with 1200 mmol Pd g-1 dry cells. Less Pd nanoparticle coating permitted cells to carry out sulfate reduction and divide, allowing the population to recover over time as surface-associated Pd diminished. Overcoming inhibition in this way was more rapid using lactate as the electron donor, compared to formate. When using formate as an electron donor, preferential Pd(II) reduction took place in the presence of 100 mM sulfate. The inhibition of important metabolic pathways using a biologically enabled casing in metal highlights a new mechanism for the development of microbial control strategies. IMPORTANCE Microbial reduction of sulfate to hydrogen sulfide is highly undesirable in several industrial settings. Some sulfate-reducing bacteria are also able to transform metal ions in their environment into metal phases that remain attached to their outer cell surface. This study demonstrates the remarkable extent to which Desulfovibrio desulfuricans can be coated with locally generated metal nanoparticles, with individual cells carrying more than 100 times their mass of palladium metal. Moreover, it reveals the effect of metal coating on metabolism and replication for a wide range of metal loadings, with bacteria unable to reduce sulfate to sulfide beyond a specific threshold. These findings present a foundation for a novel means of modulating the activity of sulfate-reducing bacteria.


Asunto(s)
Desulfovibrio desulfuricans , Desulfovibrio , Sulfuro de Hidrógeno , Bacterias/metabolismo , División Celular , Desulfovibrio/metabolismo , Desulfovibrio desulfuricans/metabolismo , Formiatos/metabolismo , Sulfuro de Hidrógeno/metabolismo , Oxidación-Reducción , Paladio/metabolismo , Sulfatos/metabolismo , Sulfuros/metabolismo
12.
J Hazard Mater ; 433: 128835, 2022 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-35398798

RESUMEN

Mercury (Hg) is a pervasive environmental pollutant and poses serious health concerns as inorganic Hg(II) can be converted to the neurotoxin methylmercury (MeHg), which bioaccumulates and biomagnifies in food webs. Phytoplankton, representing the base of aquatic food webs, can take up Hg(II) and influence MeHg production, but currently little is known about how and to what extent phytoplankton may impact Hg(II) methylation by itself or by methylating bacteria it harbors. This study investigated whether some species of phytoplankton could produce MeHg and how the live or dead phytoplankton cells and excreted algal organic matter (AOM) impact Hg(II) methylation by several known methylators, including iron-reducing bacteria (FeRB), Geobacter anodireducens SD-1 and Geobacter sulfurreducens PCA, and the sulfate-reducing bacterium (SRB) Desulfovibrio desulfuricans ND132 (or Pseudodesulfovibrio mercurii). Our results indicate that, among the 4 phytoplankton species studied, none were capable of methylating Hg(II). However, the presence of phytoplankton cells (either live or dead) from Chlorella vulgaris (CV) generally inhibited Hg(II) methylation by FeRB but substantially enhanced methylation by SRB D. desulfuricans ND132. Enhanced methylation was attributed in part to CV-excreted AOM, which increased Hg(II) complexation and methylation by ND132 cells. In contrast, inhibition of methylation by FeRB was attributed to these bacteria incapable of competing with phytoplankton for Hg(II) binding and uptake. These observations suggest that phytoplankton could play different roles in affecting Hg(II) methylation by the two groups of anaerobic bacteria, FeRB and SRB, and thus shed additional light on how phytoplankton blooms may modulate MeHg production and bioaccumulation in the aquatic environment.


Asunto(s)
Chlorella vulgaris , Desulfovibrio desulfuricans , Desulfovibrio , Mercurio , Compuestos de Metilmercurio , Bacterias/metabolismo , Chlorella vulgaris/metabolismo , Desulfovibrio/metabolismo , Desulfovibrio desulfuricans/metabolismo , Exudados y Transudados/metabolismo , Hierro/metabolismo , Mercurio/metabolismo , Mercurio/toxicidad , Metilación , Compuestos de Metilmercurio/metabolismo , Compuestos de Metilmercurio/toxicidad , Fitoplancton , Sulfatos/metabolismo
13.
Bioelectrochemistry ; 145: 108051, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35065376

RESUMEN

In this paper, we have investigated the corrosion mechanism of X80 carbon steel in the presence of nitrate reducing bacteria (NRB), sulfate reducing bacteria (SRB) or both in the Shenyang soil solution. The results show that both SRB and NRB increase the corrosion rate of steel specimens and cause pitting corrosion of steel. Electrochemical tests and weight-loss data show that the addition of NRB in the SRB-containing environment leads to the reduction of corrosion. The thermodynamic analyses confirm the competitive advantage of NRB for the nutrients (organic carbon sources and irons) and the chemical oxidation of ferrous sulfide by nitrite, which results in a mitigation in the microbiologically influence corrosion (MIC) of SRB.


Asunto(s)
Desulfovibrio desulfuricans , Desulfovibrio , Pseudomonas stutzeri , Bacterias , Biopelículas , Carbono , Corrosión , Nitratos , Suelo , Microbiología del Suelo , Acero
14.
Cell Mol Biol (Noisy-le-grand) ; 67(2): 56-65, 2021 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-34817338

RESUMEN

The study presented here aimed to assess the ability of Desulfovibrio fairfieldensis bacteria to adhere to and form biofilm on the structure of titanium used in implants. D. fairfieldensis was found in the periodontal pockets in the oral environment, indicating that these bacteria can colonize the implant-bone interface and consequently cause bone infection and implant corrosion. Plates of implantable titanium, of which surfaces were characterized by scanning electronic microscopy and Raman spectroscopy, were immersed in several suspensions of D. fairfieldensis cells containing potassium nitrate on the one hand, and artificial saliva or a sulfato-reducing bacterial culture medium on the other hand. Following various incubation timepoints bacteria were counted in different media to determine their doubling time and titanium samples are checked for and determination of the total number of adhered bacteria and biofilm formation. Adhesion of D. fairfieldensis on titanium occurs at rates ranging from 2.105 to 4.6.106 bacteria h-1cm-2 in the first 18 h of incubation on both native and implantable titanium samples. Following that time, the increase in cell numbers per h and cm2 is attributed to growth in adhered bacteria. After 30 days of incubation in a nutrient-rich medium, dense biofilms are observed forming on the implant surface where bacteria became embedded in a layer of polymers D. fairfieldensis is able of adhering to an implantable titanium surface in order to form a biofilm. Further studies are still necessary, however, to assess whether this adhesion still occurs in an environment containing saliva or serum proteins that may alter the implant surface.


Asunto(s)
Adhesión Bacteriana/fisiología , Biopelículas/crecimiento & desarrollo , Implantes Dentales/microbiología , Desulfovibrio/fisiología , Titanio/química , Desulfovibrio/clasificación , Desulfovibrio/genética , Desulfovibrio desulfuricans/fisiología , Desulfovibrio desulfuricans/ultraestructura , Humanos , Microscopía Electrónica de Rastreo , Filogenia , Proyectos Piloto , Porphyromonas/fisiología , Porphyromonas/ultraestructura , ARN Ribosómico 16S/genética
15.
J Am Chem Soc ; 143(43): 18159-18171, 2021 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-34668697

RESUMEN

[FeFe] hydrogenases are highly active enzymes for interconverting protons and electrons with hydrogen (H2). Their active site H-cluster is formed of a canonical [4Fe-4S] cluster ([4Fe-4S]H) covalently attached to a unique [2Fe] subcluster ([2Fe]H), where both sites are redox active. Heterolytic splitting and formation of H2 takes place at [2Fe]H, while [4Fe-4S]H stores electrons. The detailed catalytic mechanism of these enzymes is under intense investigation, with two dominant models existing in the literature. In one model, an alternative form of the active oxidized state Hox, named HoxH, which forms at low pH in the presence of the nonphysiological reductant sodium dithionite (NaDT), is believed to play a crucial role. HoxH was previously suggested to have a protonated [4Fe-4S]H. Here, we show that HoxH forms by simple addition of sodium sulfite (Na2SO3, the dominant oxidation product of NaDT) at low pH. The low pH requirement indicates that sulfur dioxide (SO2) is the species involved. Spectroscopy supports binding at or near [4Fe-4S]H, causing its redox potential to increase by ∼60 mV. This potential shift detunes the redox potentials of the subclusters of the H-cluster, lowering activity, as shown in protein film electrochemistry (PFE). Together, these results indicate that HoxH and its one-electron reduced counterpart Hred'H are artifacts of using a nonphysiological reductant, and not crucial catalytic intermediates. We propose renaming these states as the "dithionite (DT) inhibited" states Hox-DTi and Hred-DTi. The broader potential implications of using a nonphysiological reductant in spectroscopic and mechanistic studies of enzymes are highlighted.


Asunto(s)
Biocatálisis , Ditionita/química , Hidrogenasas/química , Proteínas Hierro-Azufre/química , Sustancias Reductoras/química , Proteínas Algáceas/química , Proteínas Bacterianas/química , Chlamydomonas reinhardtii/enzimología , Clostridium/enzimología , Desulfovibrio desulfuricans/enzimología , Hidrógeno/química , Oxidación-Reducción , Sulfitos/química , Dióxido de Azufre/química
16.
Bioelectrochemistry ; 141: 107880, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34229181

RESUMEN

Microbiologically influenced corrosion (MIC) is one of the reasons leading to the service failure of pipelines buried in the soil. The effects of sulfate-reducing bacteria (SRB) on steel corrosion without organic carbon are not clear. In this work, SRB cells were enriched in the simulated soil solution, aiming to study SRB corrosion behavior without organic carbon source using weight loss, electrochemical measurements, and surface analysis. Effects of DO on SRB corrosion were also studied. Results indicate that SRB can survive after 14 days of incubation without organic carbon source, but approximately 90% SRB have died. SRB without organic carbon source could inhibit the uniform corrosion but enhance the pitting corrosion compared with the control specimen. The corrosion rate of the control calculated from weight loss is highest with a value of (0.081 ± 0.013) mm/y. The highest localized corrosion rate of (0.306 ± 0.006) mm/y is obtained with an initial SRB count of 107 cells/mL. The presence of DO influences the steel corrosion process. Oxygen corrosion dominates for the specimens in the absence and presence of SRB with an initial count of 103 cells/mL, while SRB MIC is primary for the specimens with high SRB counts.


Asunto(s)
Desulfovibrio desulfuricans/metabolismo , Microbiología del Suelo , Suelo/química , Acero/química , Recuento de Colonia Microbiana , Corrosión , Espectroscopía Dieléctrica , Microscopía Electrónica de Rastreo , Oxígeno/metabolismo , Sulfatos/metabolismo , Propiedades de Superficie
17.
Microb Biotechnol ; 14(5): 2041-2058, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34216193

RESUMEN

Desulfovibrio desulfuricans reduces Pd(II) to Pd(0)-nanoparticles (Pd-NPs) which are catalytically active in 2-pentyne hydrogenation. To make Pd-NPs, resting cells are challenged with Pd(II) ions (uptake), followed by addition of electron donor to promote bioreduction of cell-bound Pd(II) to Pd(0) (bio-Pd). Application of radiofrequency (RF) radiation to prepared 5 wt% bio-Pd catalyst (60 W power, 60 min) increased the hydrogenation rate by 70% with no adverse impact on selectivity to cis-2-pentene. Such treatment of a 5 wt% Pd/carbon commercial catalyst did not affect the conversion rate but reduced the selectivity. Lower-dose RF radiation (2-8 W power, 20 min) was applied to the bacteria at various stages before and during synthesis of the bio-scaffolded Pd-NPs. The reaction rate (µ mol 2-pentyne converted s-1 ) was increased by ~threefold by treatment during bacterial catalyst synthesis. Application of RF radiation (2 or 4 W power) to resting cells prior to Pd(II) exposure affected the catalyst made subsequently, increasing the reaction rate by 50% as compared to untreated cells, while nearly doubling selectivity for cis 2-pentene. The results are discussed with respect to published and related work which shows altered dispersion of the Pd-NPs made following or during RF exposure.


Asunto(s)
Desulfovibrio desulfuricans , Alquenos , Transporte Biológico , Hidrogenación , Campos Magnéticos
18.
Anaerobe ; 70: 102407, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34153468

RESUMEN

Septic arthritis can occur by hematogenous seeding, direct joint inoculation, or extension of a bone infection into the joint. We report a case of septic arthritis of the hip caused by Desulfovibrio desulfuricans, an anaerobic sulfur-reducing bacteria. The patient underwent debridement followed by targeted antibiotic therapy with infection resolution.


Asunto(s)
Artritis Infecciosa/microbiología , Desulfovibrio desulfuricans/aislamiento & purificación , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Artritis Infecciosa/tratamiento farmacológico , Desulfovibrio desulfuricans/genética , Desulfovibrio desulfuricans/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad
19.
Angew Chem Int Ed Engl ; 60(16): 9055-9062, 2021 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-33450130

RESUMEN

Storage of solar energy as hydrogen provides a platform towards decarbonizing our economy. One emerging strategy for the production of solar fuels is to use photocatalytic biohybrid systems that combine the high catalytic activity of non-photosynthetic microorganisms with the high light-harvesting efficiency of metal semiconductor nanoparticles. However, few such systems have been tested for H2 production. We investigated light-driven H2 production by three novel organisms, Desulfovibrio desulfuricans, Citrobacter freundii, and Shewanella oneidensis, self-photosensitized with cadmium sulfide nanoparticles, and compared their performance to Escherichia coli. All biohybrid systems produced H2 from light, with D. desulfuricans-CdS demonstrating the best activity overall and outperforming the other microbial systems even in the absence of a mediator. With this system, H2 was continuously produced for more than 10 days with a specific rate of 36 µmol gdcw-1 h-1 . High apparent quantum yields of 23 % and 4 % were obtained, with and without methyl viologen, respectively, exceeding values previously reported.


Asunto(s)
Compuestos de Cadmio/metabolismo , Hidrógeno/metabolismo , Luz , Nanopartículas/metabolismo , Sulfuros/metabolismo , Compuestos de Cadmio/química , Citrobacter freundii/química , Citrobacter freundii/metabolismo , Desulfovibrio desulfuricans/química , Desulfovibrio desulfuricans/metabolismo , Escherichia coli/química , Escherichia coli/metabolismo , Hidrógeno/química , Nanopartículas/química , Tamaño de la Partícula , Procesos Fotoquímicos , Shewanella/química , Shewanella/metabolismo , Sulfuros/química , Propiedades de Superficie
20.
Chem Biol Drug Des ; 97(2): 231-236, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32772476

RESUMEN

The development of gut microbiota-targeted small molecules represents a promising platform for the identification of new therapeutics based on the implication of human gut bacteria with different diseases. Bacterial trimethylamine (TMA)-lyase (CutC) is expressed in gut bacteria and catalyzes the conversion of choline to TMA. The association of elevated TMA production with various disorders has directed research efforts toward identification of CutC inhibitors. Herein, we introduce peptidomimetics as a promising toolbox for the discovery of CutC inhibitors. Our approach starts with screening a library of peptidomimetics for intestinal metabolic stability followed by in vitro CutC inhibition. Compound 5 was identified from this screening platform with IC50 value of 5.9 ± 0.6 µM for CutC inhibition. Unlike previously reported CutC inhibitors, compound 5 possessed universal CutC inhibitory activity in different bacterial strains. Molecular dynamics simulations suggested a plausible binding site and inhibition mechanism for compound 5. Therefore, compound 5 is a promising lead for further structural optimization in the search for CutC-targeted small molecules.


Asunto(s)
Bacterias/enzimología , Proteínas Bacterianas/antagonistas & inhibidores , Inhibidores Enzimáticos/química , Liasas/antagonistas & inhibidores , Peptidomiméticos/química , Bacterias/aislamiento & purificación , Proteínas Bacterianas/metabolismo , Sitios de Unión , Desulfovibrio desulfuricans/enzimología , Inhibidores Enzimáticos/metabolismo , Microbioma Gastrointestinal , Humanos , Concentración 50 Inhibidora , Cinética , Liasas/metabolismo , Metilaminas/metabolismo , Simulación del Acoplamiento Molecular , Peptidomiméticos/metabolismo
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