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2011
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Sulfur starvation induces an Fe-replete response and attenuates virulence pathways in Pseudomonas aeruginosa PAO1
(2025-11-03) Zeczycki, Tonya N.; Ellis, Holly R.; Aworh, Mabel Kamweli
Understanding bacterial responses to nutrient limitation is critical for developing targeted antimicrobial strategies. Sulfur starvation uniquely induces not only genes responsible for sulfur scavenging but also prominent antioxidant defenses. However, the biological rationale behind the simultaneous induction of antioxidants during sulfur limitation remains largely unexplored. Our study addresses this gap by integrating transcriptomic, proteomic, and targeted metabolomic data from Pseudomonas aeruginosa PAO1 grown under sulfur-free conditions. Results: As anticipated, transcripts and proteins involved in sulfur assimilation and metabolism—including members of the msu, ssu, and cys operons—were upregulated, along with key antioxidant enzymes such as Ohr, LsfA, and SodB. Unexpectedly, however, genes encoding iron uptake systems (pyoverdine, pyochelin, and heme metabolism operons) were markedly downregulated, while iron storage proteins (BfrB, Dps, and PA4880) were elevated, indicating an iron-replete metabolic state. Further targeted metabolic profiling and iron quantification assays confirmed reduced Fe acquisition and diminished extracellular levels of siderophore and phenazine metabolites. This shift in iron homeostasis correlated with the repression of multiple virulence factors regulated by Fur and PrrF, including quorum-sensing components, efflux pumps, and phenazine biosynthesis enzymes. Conclusion: Our integrative analysis reveals that sulfur starvation critically regulates iron homeostasis by linking reduced Fe uptake to the induction of antioxidant defenses. This iron-buffering response likely mitigates oxidative damage from unincorporated Fe, representing a protective metabolic adaptation. Additionally, the concurrent attenuation of virulence pathways suggests that targeting sulfur metabolism could disrupt iron-dependent virulence gene regulation, offering therapeutic insights into nutritional immunity strategies. Collectively, our findings uncover a novel sulfur-iron axis that plays a central role in oxidative stress management and pathogenicity modulation in bacteria. Graphical abstract Using high-throughput RNA-sequencing and proteomics techniques, we identified genes and metabolites differentially expressed during sulfur starvation in P. aeruginosa grown in minimal media. Additional experiments using a range of biophysical techniques were used to quantify select metabolites and Fe. Overall, we found that sulfur starvation induced an Fe-replete response, characterized by the repression of Fe uptake pathways and the upregulation of Fe storage genes.
Accelerating the translation of findings from the MoTrPAC study to benefit clinical care: a qualitative analysis
(2025-10-28) Accelerating the translation of findings from the MoTrPAC study to benefit clinical care: a qualitative analysis; Houmard, Joseph A.
The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a large-scale research study aimed at elucidating the effects of exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. To take a first step toward achieving a goal of rapid dissemination, a qualitative analysis among frontline clinicians was conducted to identify the perceived clinical relevance of exercise research, MoTrPAC discoveries, and optimal ways to disseminate these results to key stakeholders. Methods: A convenience sample of 12 clinicians in internal medicine, family medicine, and emergency medicine agreed to participate in one-on-one interviews. Interviews were conducted over the phone by a member of the Wake Forest Qualitative and Patient-Reported Outcomes (Q-PRO) Shared Resource. Transcripts were stored and coded in ATLAS.ti version 24 software. Two Q-PRO members developed code summaries, which were synthesized into themes and organized using principles of reflexive thematic analysis. Results: Clinicians (n = 12) were predominantly male (n = 7), non-Hispanic White (n = 5), located in California (n = 10), and practiced in a Primary Care/Family Medicine setting (n = 6). Clinicians reported underuse of exercise testing due to provider-level and patient-level barriers. While they valued exercise research, they emphasized the need for clear, practical takeaways and preferred direct dissemination strategies. Conclusions: These interviews highlighted the variable nature of exercise research dissemination and implementation and are the first steps toward shaping the dissemination of valuable scientific discoveries from the MoTrPAC study.
In silico genomic insights into bacteriophages infecting ESBL-producing Escherichia coli from human, animal, and environmental sources
(2025-04-08) Aworh, Mabel Kamweli
The emergence of antimicrobial resistance (AMR) in Escherichia coli, particularly extended-spectrum beta-lactamase-producing E. coli (ESBL-EC), is a global public health concern. Bacteriophages (phages) play a significant role in bacterial evolution and the spread of antibiotic resistance genes (ARGs). This study investigates prophages integrated within ESBL-EC genomes to assess their diversity, gene content, and potential contributions to ESBL-EC persistence across human, animal, and environmental reservoirs. Between May and December 2020, a cross-sectional study was conducted in Abuja and Lagos, collecting 448 stool, cecal, and environmental samples from abattoir workers, slaughtered cattle, and the abattoir environment. ESBL-EC genomes from these samples, obtained in an earlier study, were analyzed for phage regions using PHASTER. Intact prophages were analyzed in silico using computational tools to detect ARGs, ESBL genes, virulence factors, and heavy metal resistance. Their genomic relationships were examined with statistical significance of p < 0.05. Results Out of 448 samples, ESBL-EC prevalence was 21.7% (97/448). Among 97 ESBL-EC isolates, 646 prophage regions were detected, with 30% (194/646) classified as intact phages. Among the 158 phages with genus assignments, Punavirus was the most prevalent (60.1%). Escherichia was the most frequent predicted host (308/646), particularly in cattle (n = 143) and human (n = 124) sources. Among ESBL-EC genomes, 83.5% (81/97) with intact phages carried phage-associated ARGs, 76.3% (74/97) carried phage-associated ESBL genes, 18.6% (18/97) harbored phage-associated virulence factors, 15.5% (15/97) contained phage-associated plasmids, and 10.3% (10/97) had heavy metal resistance. The most prevalent phage-associated ARGs detected were qnrS1 (73/81) and blaCTX-M-15 (72/81). Two isolates recovered from abattoir workers carried two phage-like plasmids, each harboring either tet(A) or blaCTX-M-55 gene. The predominant phage lifestyles were temperate (n = 182), mainly in the Peduoviridae family, and lytic (n = 12) in the Punavirus genus. Conclusion: This is the first study in Nigeria to characterize phages in ESBL-EC isolates at the One Health interface. The presence of intact phages in humans, animals, and the environment underscores the complex interactions shaping phage ecology. The discovery of ARGs, virulence genes, and heavy metal resistance within prophages suggests a potential role in AMR dissemination. Future research should focus on elucidating mechanisms of ARG transfer mediated by phages in One Health settings.
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