RESUMO
The fight against bacterial antibiotic resistance must be given critical attention to avert the current and emerging crisis of treating bacterial infections due to the inefficacy of clinically relevant antibiotics. Intrinsic genetic mutations and transferrable antibiotic resistance genes (ARGs) are at the core of the development of antibiotic resistance. However, traditional alignment methods for detecting ARGs have limitations. Artificial intelligence (AI) methods and approaches can potentially augment the detection of ARGs and identify antibiotic targets and antagonistic bactericidal and bacteriostatic molecules that are or can be developed as antibiotics. This review delves into the literature regarding the various AI methods and approaches for identifying and annotating ARGs, highlighting their potential and limitations. Specifically, we discuss methods for (1) direct identification and classification of ARGs from genome DNA sequences, (2) direct identification and classification from plasmid sequences, and (3) identification of putative ARGs from feature selection.
RESUMO
Antimicrobial resistance (AMR) is a global threat to human health since infections caused by antimicrobial-resistant bacteria are life-threatening conditions with minimal treatment options. Bacteria become resistant when they develop the ability to overcome the compounds that are meant to kill them, i.e., antibiotics. The increasing number of resistant pathogens worldwide is contrasted by the slow progress in the discovery and production of new antibiotics. About 700,000 global deaths per year are estimated as a result of drug-resistant infections, which could escalate to nearly 10 million by 2050 if we fail to address the AMR challenge. In this study, we collected and isolated bacteria from the environment to screen for antibiotic resistance. We identified several bacteria that showed resistance to multiple clinically relevant antibiotics when tested in antibiotic susceptibility disk assays. We also found that two strains, identified as Pantoea rodasii RIT 836 and Pseudomonas endophytica RIT 838 via whole genome sequencing and annotation, produce bactericidal compounds against both Gram-positive and Gram-negative bacteria in disc-diffusion inhibitory assays. We mined the two strains' whole-genome sequences to gain more information and insights into the antibiotic resistance and production by these bacteria. Subsequently, we aim to isolate, identify, and further characterize the novel antibiotic compounds detected in our assays and bioinformatics analysis.
Assuntos
Antibacterianos , Anti-Infecciosos , Pantoea , Humanos , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Bactérias Gram-Positivas , Pseudomonas/genética , Sequenciamento Completo do GenomaRESUMO
Antimicrobial resistance (AMR) is one of the most alarming global public health challenges of the 21st century. Over 3 million antimicrobial-resistant infections occur in the United States annually, with nearly 50,000 cases being fatal. Innovations in drug discovery methods and platforms are crucial to identify novel antibiotics to combat AMR. We present the isolation and characterization of potentially novel antibiotic lead compounds produced by the cross-feeding of two rhizosphere bacteria, Acinetobacter sp. RIT 592 and Exiguobacterium sp. RIT 594. We used solid-phase extraction (SPE) followed by liquid chromatography (LC) to enrich antibiotic extracts and subsequently mass spectrometry (MS) analysis of collected fractions for compound structure identification and characterization. The MS data were processed through the Global Natural Product Social Molecular Networking (GNPS) database. The supernatant from RIT 592 induced RIT 594 to produce a cocktail of antimicrobial compounds active against Gram-positive and negative bacteria. The GNPS analysis indicated compounds with known antimicrobial activity in the bioactive samples, including oligopeptides and their derivatives. This work emphasizes the utility of microbial community-based platforms to discover novel clinically relevant secondary metabolites. Future work includes further structural characterization and antibiotic activity evaluation of the individual compounds against pathogenic multidrug-resistant (MDR) bacteria.
RESUMO
OBJECTIVE: Antibiotic resistant infections have become a global health crisis causing 1.2 million deaths worldwide in 2019 [1]. In a previous study, we identified a bacterium from a rare genus, Yimella, and found in an initial antibiotic screening that they produce broad-spectrum bactericidal compounds [2]. Herein, we focus on the characterization of these potential novel antimicrobial compounds produced by Yimella sp. RIT 621. RESULTS: We used solid-phase extraction and C18 reverse-phase chromatography to isolate the antibiotic-active compounds found in organic extracts from liquid cultures of Yimella sp. RIT 621. We tracked the antimicrobial activity by testing the extracts in disc diffusion inhibitory assays and observed its increase after each purification stage.
Assuntos
Antibacterianos , Anti-Infecciosos , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , CromatografiaRESUMO
We report the whole-genome sequence and annotation of two antibiotic-resistant bacteria, Enterobacter roggenkampii RIT 834 and Acinetobacter pittii RIT 835, isolated from disposed masks. We found that these strains are resistant to five of seven commonly used antibiotics and that they produce bactericidal compounds against Escherichia coli.
RESUMO
The widespread use of plastics has led to their increasing presence in the environment and subsequent pollution. Some microorganisms degrade plastics in natural ecosystems and the associated metabolic pathways can be studied to understand the degradation mechanisms. Polystyrene (PS) is one of the more recalcitrant plastic polymers that is degraded by only a few bacteria. Exiguobacterium is a genus of Gram-positive poly-extremophilic bacteria known to degrade PS, thus being of biotechnological interest, but its biochemical mechanisms of degradation have not yet been elucidated. Based solely on genome annotation, we initially proposed PS degradation by Exiguobacterium sp. RIT 594 via depolymerization and epoxidation catalyzed by a ring epoxidase. However, Fourier transform infrared (FTIR) spectroscopy analysis revealed an increase of carboxyl and hydroxyl groups with biodegradation, as well as of unconjugated C-C double bonds, both consistent with dearomatization of the styrene ring. This excludes any aerobic pathways involving side chain epoxidation and/or hydroxylation. Subsequent experiments confirmed that molecular oxygen is critical to PS degradation by RIT 594 because degradation ceased under oxygen-deprived conditions. Our studies suggest that styrene breakdown by this bacterium occurs via the sequential action of two enzymes encoded in the genome: an orphan aromatic ring-cleaving dioxygenase and a hydrolase.
RESUMO
We report the isolation, whole-genome sequencing, and annotation of Enterobacter sp. strain RIT 637, Pseudomonas sp. strain RIT 778, and Deinococcus sp. strain RIT 780. Disk diffusion assays using spent medium demonstrated that all bacteria produced bactericidal compounds against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Staphylococcus aureus ATCC 25923.