An updated genome-scale metabolic network reconstruction of Pseudomonas aeruginosa PA14 to characterize mucin-driven shifts in bacterial metabolism.

Mucins are present in mucosal membranes throughout the body and play a key role in the microbe clearance and infection prevention. Understanding the metabolic responses of pathogens to mucins will further enable the development of protective approaches against infections. We update the genome-scale metabolic network reconstruction (GENRE) of one such pathogen, Pseudomonas aeruginosa PA14, through metabolic coverage expansion, format update, extensive annotation addition, and literature-based curation to produce iPau21.

Multidimensional Clinical Surveillance of Pseudomonas aeruginosa Reveals Complex Relationships between Isolate Source, Morphology, and Antimicrobial Resistance.

Antimicrobial susceptibility in Pseudomonas aeruginosa is dependent on a complex combination of host and pathogen-specific factors. Through the profiling of 971 clinical P. aeruginosa isolates from 590 patients and collection of paired patient metadata, we show that antimicrobial resistance is associated with not only patient-centric factors (e.

Untargeted Metabolomics Reveals Species-Specific Metabolite Production and Shared Nutrient Consumption by Pseudomonas aeruginosa and Staphylococcus aureus.

While bacterial metabolism is known to impact antibiotic efficacy and virulence, the metabolic capacities of individual microbes in cystic fibrosis lung infections are difficult to disentangle from sputum samples. Here, we show that untargeted metabolomic profiling of supernatants of multiple strains of Pseudomonas aeruginosa and Staphylococcus aureus grown in monoculture in synthetic cystic fibrosis media (SCFM) reveals distinct species-specific metabolic signatures despite intraspecies metabolic variability. We identify a set of 15 metabolites that were significantly consumed by both P.

Evaluating the efficacy of an algae-based treatment to mitigate elicitation of antibiotic resistance.

Antibiotics in the effluents of municipal wastewater treatment plants (WWTP) may create selective pressures to induce antibiotic resistance in bacteria downstream. This study evaluates ciprofloxacin (CIP) removal by a freshwater alga, Scenedesmus dimorphus, to assess the efficacy of algae-based tertiary treatment in reducing effluent-induced CIP resistance. Results show significant CIP removal in light-exposed samples without algae and experimental algae (EA) samples: 53% and 93%, respectively, over 144 h.

Integrated Experimental and Computational Analyses Reveal Differential Metabolic Functionality in Antibiotic-Resistant Pseudomonas aeruginosa.

Metabolic adaptations accompanying the development of antibiotic resistance in bacteria remain poorly understood. To study this relationship, we profiled the growth of lab-evolved antibiotic-resistant lineages of the opportunistic pathogen Pseudomonas aeruginosa across 190 unique carbon sources. Our data revealed that the evolution of antibiotic resistance resulted in systems-level changes to growth dynamics and metabolic phenotype.

Biomedical applications of genome-scale metabolic network reconstructions of human pathogens.

The growing global threat of antibiotic resistant human pathogens has coincided with improved methods for developing and using genome-scale metabolic network reconstructions. Consequently, there has been an increase in the number of high-quality reconstructions of relevant human and zoonotic pathogens. Novel biomedical applications of pathogen reconstructions focus on three key aspects of pathogen behavior: the evolution of antibiotic resistance, virulence factor production, and host-pathogen interactions.

Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology.

While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine trials.

Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells.

Elevated inflammatory cytokines (EMCs) at mucosal surfaces have been associated with HIV susceptibility, but the underlying mechanisms remain unclear. We characterized the soluble mucosal proteome associated with elevated cytokine expression in the female reproductive tract. A scoring system was devised based on the elevation (upper quartile) of at least three of seven inflammatory cytokines in cervicovaginal lavage.