Leveraging Graph Neural Networks for MIC Prediction in Antimicrobial Resistance Studies.

Antimicrobial resistance (AMR) poses a significant challenge in healthcare and public health, with organisms such as nontyphoidal Salmonella leading the way due to their escalating resistance to antimicrobial agents. This situation severely complicates the management and containment of diseases, highlighting the urgent need for more effective techniques to assess antimicrobial susceptibility. Conventional methods, including the broth microdilution technique for determining Minimum Inhibitory Concentrations (MICs), are time-consuming and require extensive manual effort.

Characterization of an Arginine Decarboxylase from by Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry.

Polyamines are polycations derived from amino acids that play an important role in proliferation and growth in almost all living cells. In (the pneumococcus), modulation of polyamine metabolism not only plays an important regulatory role in central metabolism, but also impacts virulence factors such as the capsule and stress responses that affect survival in the host. However, functional annotation of enzymes from the polyamine biosynthesis pathways in the pneumococcus is based predominantly on computational prediction.

Impact of Difluoromethylornithine and AMXT 1501 on Gene Expression and Capsule Regulation in .

(Spn), a Gram-positive bacterium, poses a significant threat to human health, causing mild respiratory infections to severe invasive conditions. Despite the availability of vaccines, challenges persist due to serotype replacement and antibiotic resistance, emphasizing the need for alternative therapeutic strategies. This study explores the intriguing role of polyamines, ubiquitous, small organic cations, in modulating virulence factors, especially the capsule, a crucial determinant of Spn's pathogenicity.

Predicting MIC and Deciphering Genomic Determinants of Antibiotic Resistance and Susceptibility.

spp., a leading cause of foodborne illness, is a formidable global menace due to escalating antimicrobial resistance (AMR). The evaluation of minimum inhibitory concentration (MIC) for antimicrobials is critical for characterizing AMR.

Predicting foodborne pathogens and probiotics taxa within poultry-related microbiomes using a machine learning approach.

Background: Microbiomes that can serve as an indicator of gut, intestinal, and general health of humans and animals are largely influenced by food consumed and contaminant bioagents. Microbiome studies usually focus on estimating the alpha (within sample) and beta (similarity/dissimilarity among samples) diversities. This study took a combinatorial approach and applied machine learning to microbiome data to predict the presence of disease-causing pathogens and their association with known/potential probiotic taxa.

An ensemble learning approach to identify pastured poultry farm practice variables and soil constituents that promote prevalence.

Animal sourced foods including contaminated poultry meat and eggs contribute to human non-typhoidal salmonellosis, a foodborne zoonosis. Prevalence of in pastured poultry production systems can lead to contamination of the final product. Identification of farm practices that affect prevalence is critical for implementing control measures to ensure the safety of these products.

Preharvest Environmental and Management Drivers of Multidrug Resistance in Major Bacterial Zoonotic Pathogens in Pastured Poultry Flocks.

Due to nutritional benefits and perceived humane ways of treating the animals, the demand for antibiotic-free pastured poultry chicken has continued to be steadily rise. Despite the non-usage of antibiotics in pastured poultry broiler production, antibiotic resistance (AR) is reported in zoonotic poultry pathogens. However, factors that drive multidrug resistance (MDR) in pastured poultry are not well understood.

Difluoromethylornithine (DFMO) and AMXT 1501 inhibit capsule biosynthesis in pneumococci.

Polyamines are small cationic molecules that have been linked to various cellular processes including replication, translation, stress response and recently, capsule regulation in Streptococcus pneumoniae (Spn, pneumococcus). Pneumococcal-associated diseases such as pneumonia, meningitis, and sepsis are some of the leading causes of death worldwide and capsule remains the principal virulence factor of this versatile pathogen. α-Difluoromethyl-ornithine (DFMO) is an irreversible inhibitor of the polyamine biosynthesis pathway catalyzed by ornithine decarboxylase and has a long history in modulating cell growth, polyamine levels, and disease outcomes in eukaryotic systems.

The Effect of Impaired Polyamine Transport on Pneumococcal Transcriptome.

Infections due to , a commensal in the nasopharynx, still claim a significant number of lives worldwide. Genome plasticity, antibiotic resistance, and limited serotype coverage of the available polysaccharide-based conjugate vaccines confounds therapeutic interventions to limit the spread of this pathogen. Pathogenic mechanisms that allow successful adaption and persistence in the host could be potential innovative therapeutic targets.

Arginine Decarboxylase Is Essential for Pneumococcal Stress Responses.

Polyamines such as putrescine, cadaverine, and spermidine are small cationic molecules that play significant roles in cellular processes, including bacterial stress responses and host-pathogen interactions. is an opportunistic human pathogen, which causes several diseases that account for significant morbidity and mortality worldwide. As it transits through different host niches, is exposed to and must adapt to different types of stress in the host microenvironment.

SP_0916 Is an Arginine Decarboxylase That Catalyzes the Synthesis of Agmatine, Which Is Critical for Capsule Biosynthesis in .

The global burden of invasive pneumococcal diseases, including pneumonia and sepsis, caused by , a Gram-positive bacterial pathogen, remains a major global health risk. The success of pneumococcus as a pathogen can be attributed to its ability to regulate the synthesis of capsular polysaccharide (CPS) during invasive disease. We previously reported that deletion of a putative lysine decarboxylase (LDC; ΔSP_0916) in pneumococcal serotype 4 (TIGR4) results in reduced CPS.

Polyamine Synthesis Effects Capsule Expression by Reduction of Precursors in .

(pneumococcus, Spn) colonizes the human nasopharynx asymptomatically but can cause infections such as otitis media, and invasive pneumococcal disease such as community-acquired pneumonia, meningitis, and sepsis. Although the success of Spn as a pathogen can be attributed to its ability to synthesize and regulate capsular polysaccharide (CPS) for survival in the host, the mechanisms of CPS regulation are not well-described. Recent studies from our lab demonstrate that deletion of a putative polyamine biosynthesis gene (Δ) in Spn TIGR4 results in the loss of the capsule.

The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein Expression.

Invasive infections caused by , a commensal in the nasopharynx, pose significant risk to human health. Limited serotype coverage by the available polysaccharide-based conjugate vaccines coupled with increasing incidence of antibiotic resistance complicates therapeutic strategies. Bacterial physiology and metabolism that allows pathogens to adapt to the host are a promising avenue for the discovery of novel therapeutics.