The Multiomics Response of Bacillus subtilis to Simultaneous Genetic and Environmental Perturbations DOI Creative Commons
Li Liu, Gaoyang Li, Huansheng Cao

et al.

Microorganisms, Journal Year: 2023, Volume and Issue: 11(8), P. 1949 - 1949

Published: July 30, 2023

How bacteria respond at the systems level to both genetic and environmental perturbations imposed same time is one fundamental yet open question in biology. Bioengineering or synthetic biology provides an ideal system for studying such responses, as engineered strains always have changes opposed wildtypes are grown conditions which often change during growth maximal yield of desired products. So, were used address outstanding question. Two Bacillus subtilis (MT1 MT2) created previously overproduction N-acetylglucosamine (GlcNAc), environment with a carbon shift from glucose xylose culture system. We had four groups: (1) wildtype (WT) t1; (2) WT t2; (3) mutant (MT1) (4) MT1 t2. By measuring transcriptomes metabolomes, we found that GlcNAc-producing mutants, particularly MT2, higher than but displayed smaller maximum rate wildtype, despite reaching carrying capacity. Underlying observed growth, pathways leading gene expression associated metabolite concentrations t1 bioenergetics, there was energy supply terms ATP GTP, state metric timepoints. Additionally, most top key precursor metabolites equally abundant either Besides that, prominent feature high consistency between transcriptomics metabolomics revealing response. First, metabolomes revealed PCA clusters groups. Second, important functions enriched by overlapped, amino acid metabolism ABC transport. Strikingly, these overlapped those genes showing (positive negative) correlation metabolites. Furthermore, also KEGG identified using weighted coexpression network analysis. All findings suggest responses simultaneous well coordinated metabolic transcriptional levels: they rely heavily on core does not differ much, while transport important. This serves design guide bioengineering, biology,

Language: Английский

Design and Synthesis of Novel Antimicrobial Agents DOI Creative Commons
Zeinab Breijyeh, Rafik Karaman

Antibiotics, Journal Year: 2023, Volume and Issue: 12(3), P. 628 - 628

Published: March 22, 2023

The necessity for the discovery of innovative antimicrobials to treat life-threatening diseases has increased as multidrug-resistant bacteria spread. Due antibiotics’ availability over counter in many nations, antibiotic resistance is linked overuse, abuse, and misuse these drugs. World Health Organization (WHO) recognized 12 families that present greatest harm human health, where options therapy are extremely limited. Therefore, this paper reviews possible new ways development novel classes antibiotics which there no pre-existing bacterial pathogens. By utilizing research technology such nanotechnology computational methods (such silico Fragment-based drug design (FBDD)), been an improvement antimicrobial actions selectivity with target sites. Moreover, alternatives, peptides, essential oils, anti-Quorum sensing agents, darobactins, vitamin B6, bacteriophages, odilorhabdins, 18β-glycyrrhetinic acid, cannabinoids. Additionally, repurposing ticagrelor, mitomycin C, auranofin, pentamidine, zidovudine) synthesis antibacterial agents (including lactones, piperidinol, sugar-based bactericides, isoxazole, carbazole, pyrimidine, pyrazole derivatives) represent approaches treating infectious diseases. Nonetheless, prodrugs (e.g., siderophores) have recently shown be excellent platform a generation better efficacy against bacteria. Ultimately, combat resistant stop spread illnesses, regulations public education regarding use hospitals agricultural sector should combined technological advancements.

Language: Английский

Citations

69
Whole Genome Sequencing: Applications in Clinical Bacteriology DOI Creative Commons
Abu Salim Mustafa

Medical Principles and Practice, Journal Year: 2024, Volume and Issue: 33(3), P. 185 - 197

Published: Jan. 1, 2024

The success in determining the whole genome sequence of a bacterial pathogen was first achieved 1995 by complete nucleotide <i>Haemophilus influenzae</i> Rd using chain-termination method established Sanger et al. 1977 and automated Hood 1987. However, this technology laborious, costly, time-consuming. Since 2004, high-throughput next-generation sequencing technologies have been developed, which are highly efficient, require less time, cost-effective for (WGS) all organisms, including pathogens. In recent years, data obtained WGS coupled with bioinformatics analyses sequenced genomes projected to revolutionize clinical bacteriology. used identification species, strains, genotypes from cultured organisms directly specimens. has also helped resistance antibiotics detection antimicrobial genes point mutations. Furthermore, epidemiological tracking surveillance pathogenic bacteria healthcare settings as well communities. This review focuses on applications

Language: Английский

Citations

5
Genomic insights into fish pathogenic bacteria: A systems biology perspective for sustainable aquaculture DOI
Raju Sasikumar, S. Saranya,

L. Lourdu Lincy

et al.

Fish & Shellfish Immunology, Journal Year: 2024, Volume and Issue: unknown, P. 109978 - 109978

Published: Oct. 1, 2024

Language: Английский

Citations

5
Combating antibiotic resistance: mechanisms, challenges, and innovative approaches in antibacterial drug development DOI Creative Commons

Aiswarya Rajesh,

Sunita Pawar,

Kruthi Doriya

et al.

Published: Jan. 26, 2025

Antibiotic resistance is a significant threat to public health and drug development, driven largely by the overuse misuse of antibiotics in medical agricultural settings. As bacteria adapt evade current drugs, managing bacterial infections has become increasingly challenging, leading prolonged illnesses, higher healthcare costs, increased mortality. This review explores critical role fighting mechanisms that enable resist them. Key discussed include carvacrol, dalbavancin, quinolones, fluoroquinolones, zoliflodacin, each with unique actions against pathogens. Bacteria have evolved complex strategies, such as enzyme production neutralize modifying targets, using efflux pumps remove antibiotics, significantly reducing efficacy. Additionally, examines challenges antibiotic including declining discovery rate novel drugs due high costs regulatory complexities. Innovative approaches, structure-based design, combination therapies, new delivery systems, are highlighted for their potential create compounds enhanced action resistant strains. provides valuable insights researchers developers aiming combat advance development robust antibacterial therapies future security.

Language: Английский

Citations

0
The protective role of commensal gut microbes and their metabolites against bacterial pathogens DOI Creative Commons
Liqin Cheng, Mário S. P. Correia, Shawn M. Higdon

et al.

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: May 26, 2024

Multidrug-resistant microorganisms have become a major public health concern around the world. The gut microbiome is gold mine for bioactive compounds that protect human body from pathogens. We used multi-omics approach integrated whole-genome sequencing (WGS) of 74 commensal isolates with metabolome analysis to discover their metabolic interaction Salmonella and other antibiotic-resistant evaluated differences in functional potential these selected based on WGS annotation profiles. Furthermore, top altered metabolites co-culture supernatants were identified including series dipeptides examined ability prevent growth various bacteria. Our results provide compelling evidence produces metabolites, compound class can potentially be applied anti-infection medication, especially against established pipeline discovery validation as novel candidates multidrug-resistant infections represents new avenue antimicrobial lead structures.

Language: Английский

Citations

3
Maltodextrin-binding protein as a key factor in Cronobacter sakazakii survival under desiccation stress DOI Creative Commons
Juan Xue, Jun Lv,

Lanfang Liu

et al.

Food Research International, Journal Year: 2023, Volume and Issue: 177, P. 113871 - 113871

Published: Dec. 16, 2023

Cronobacter sakazakii (C. sakazakii) is a notorious pathogen responsible for infections in infants and newborns, often transmitted through contaminated infant formula. Despite the use of traditional pasteurization methods, which can reduce microbial contamination, there remains significant risk pathogenic C. surviving due to its exceptional stress tolerance. In our study, we employed comparative proteomic approach by comparing wild-type strains with gene knockout identify essential genes crucial successful survival during desiccation. Our investigation revealed significance envZ-ompR, recA, flhD cassettes contributing desiccation tolerance sakazakii. Furthermore, profiling, identified maltodextrin-binding protein encoded ESA_03421 as potential factor influencing dry This regulated EnvZ-OmpR, RecA, FlhD. Notably, resulted 150% greater reduction Log CFU compared Overall, findings offer valuable insights into mechanisms underlying provide targets development new antimicrobial strategies aimed at reducing newborns.

Language: Английский

Citations

8
Flankophile: a bioinformatic pipeline for prokaryotic genomic synteny analysis DOI Creative Commons
Alix Vincent Thorn, Frank M. Aarestrup, Patrick Munk

et al.

Microbiology Spectrum, Journal Year: 2023, Volume and Issue: 12(1)

Published: Dec. 12, 2023

ABSTRACT Analysis of flanking region sequences can be useful when comparing mobile prokaryotic from different bacterial isolates or metagenomes. Here, we report a new bioinformatics tool, pipeline called Flankophile, which analyze regions and sequence variants. The main feature Flankophile is that it visualizes synteny variants in publication-ready plots with distance trees, gene annotations, metadata. Antimicrobial resistance significant threat to human health, surveillance the spread antimicrobial essential. study acquired genes (ARGs) an obvious use case for due typically diverse genetic context genes. Flanking offer stronger epidemiological signal than alone. To demonstrate applied 2,057 sequenced 273 metagenomes humans pigs Denmark compared ARGs found each host reservoir. Gene variant results showed just ca. 4% all unique ARG ( N = 1,052) were detected samples both pigs. analysis frequently this multiple examples where entire 3,000-base pair was identical hosts but also cases no overlap observed, clustering complete separation humans. IMPORTANCE enables visualization interest on large data sets one step consistent manner. A specific tool automated has not been developed before, will make easier accessible more people. especially field genomic epidemiology information instrumental rejecting supporting possibility recent common source same samples.

Language: Английский

Citations

7
ProkDBP: Toward more precise identification of prokaryoticDNAbinding proteins DOI
Upendra Kumar Pradhan, Prabina Kumar Meher,

Sanchita Naha

et al.

Protein Science, Journal Year: 2024, Volume and Issue: 33(6)

Published: May 15, 2024

Abstract Prokaryotic DNA binding proteins (DBPs) play pivotal roles in governing gene regulation, replication, and various cellular functions. Accurate computational models for predicting prokaryotic DBPs hold immense promise accelerating the discovery of novel proteins, fostering a deeper understanding biology, facilitating development therapeutics targeting potential disease interventions. However, existing generic prediction often exhibit lower accuracy DBPs. To address this gap, we introduce ProkDBP, machine learning‐driven model For prediction, total nine shallow learning algorithms five deep were utilized, with demonstrating higher performance metrics compared to their counterparts. The light gradient boosting (LGBM), coupled evolutionarily significant features selected via random forest variable importance measure (RF‐VIM) yielded highest five‐fold cross‐validation accuracy. achieved auROC (0.9534) auPRC (0.9575) among 14 evaluated. Additionally, ProkDBP demonstrated substantial an independent dataset, exhibiting values (0.9332) (0.9371). Notably, when benchmarked against several cutting‐edge models, showcased superior predictive Furthermore, promote accessibility usability, ( https://iasri-sg.icar.gov.in/prokdbp/ ) is available as online tool, enabling free access interested users. This tool stands contribution, enhancing repertoire resources accurate efficient

Language: Английский

Citations

2
L-Ornithine derivatives with structural hetaryl and alkyl moiety: Synthesis and antibacterial activity DOI Creative Commons
T. G. Bodrova, U. A. Budanova,

Yu. L. Sebyakin

et al.

Fine Chemical Technologies, Journal Year: 2024, Volume and Issue: 19(3), P. 202 - 213

Published: July 5, 2024

Objectives . Cationic amphiphiles and antimicrobial peptidomimetics are widely investigated as antibacterial agents due to their membrane-active mechanism of action. Particular attention is focused on the rational design compounds in this class achieve high activity. The aim present work synthesize bivalent cationic with L-ornithine a branching element evaluate effectiveness differ terms hydrophobicity variation N-terminal aliphatic amino acids polar block alternation dialkyl alkyl-hetaryl radicals lipophilic block. Methods For synthesis nonpolar fragments amphiphiles, methods for alkylation amines alkyl bromides presence carbonate salts were used. formation amide bonds derivatives was carried out using carbodiimide method. reaction products recovery from mixture, column chromatography silica gel aluminum oxide activated Brockmann Grade II activity synthesized against gram-positive B. subtilis 534 gram-negative E. coli M17 bacterial strains evaluated. Minimum inhibitory concentration (MIC) values recorded serial microdilution method nutrient medium. Results Developed schemes preparation based presented. Differences structure (glycine, β-alanine, γ-aminobutyric acid (GABA)), length (C 8 , C 12 ), or an indole moiety, used target compounds. demonstrated. most active lipoamino terminal GABA residues asymmetrical non-polar (tryptamyl–dodecylamine). MIC 0.39 μg/mL bacteria 1.56 bacteria. A derivative symmetrical moiety dioctylamine demonstrated 0.78 3.12 Conclusions Nine new synthesized. obtained confirmed by nuclear magnetic resonance 1 H spectroscopy mass spectrometry data. Leading both determined. influence degree lipophilicity asymmetric level exhibited

Language: Английский

Citations

2
Combined transcriptome and metabolome analysis revealed the antimicrobial mechanism of Griseorhodin C against Methicillin-resistant Staphylococcus aureus DOI Creative Commons

Jingyang Liao,

Jiaxing Tan, Xiaobo Li

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 4, 2024

The global rise of multidrug-resistant pathogens, particularly Methicillin-resistant Staphylococcus aureus (MRSA), has become a critical public health concern, necessitating the urgent discovery new antimicrobial agents. Griseorhodin C, hydroxyquinone compound isolated from Streptomyces, demonstrated significant inhibitory effects against MRSA. In this study, we employed comprehensive approach combining transcriptome and metabolome analyses to investigate underlying mechanism C. Our findings reveal that C interferes with multiple bacterial metabolic pathways, including those essential for biosynthesis metabolism amino acids, purine energy metabolism, ultimately leading growth inhibition cell death. Notably, showed superior compared clinical standard, vancomycin, both in vivo vitro. These results highlight potential as promising candidate development therapeutic strategies aimed at combating MRSA infections. study underscores importance exploring natural products sources novel antibiotics ongoing fight resistance.

Language: Английский

Citations

2