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Articles 1 - 6 of 6
Full-Text Articles in Pathogenic Microbiology
Nucleotide-Derived Bacterial Alarmones Attenuate The Induction Of Type-I Interferon Responses In A Murine Macrophage Reporter Cell Line, Ryan P. Kilduff, Erin B. Purcell, Lisa M. Shollenberger
Nucleotide-Derived Bacterial Alarmones Attenuate The Induction Of Type-I Interferon Responses In A Murine Macrophage Reporter Cell Line, Ryan P. Kilduff, Erin B. Purcell, Lisa M. Shollenberger
Chemistry & Biochemistry Faculty Publications
The stringent response is a well-studied phenomenon in many bacterial systems and regulates resource-consuming activities such as transcription, translation, and replication. The stringent response is a well-conserved signaling framework, as are the nucleotide-derived signaling mediators, collectively referred to as (p)ppGpp or as alarmones. There is a wealth of research evaluating nucleotide-derived alarmone signaling in bacterial models, however, their potential to modulate innate immune signaling has not yet been evaluated. Several common pathogen-synthesized molecules, such as lipopolysaccharide (LPS) and cyclic-di-AMP (c-di-AMP), act as pathogen-associated molecular patterns (PAMPs), which are common patterns that alert the innate immune system of bacterial infection. The …
Reiq-Mediated Alarmone Signalling Regulates Growth, Stress-Induced Biofilm Formation And Spore Accumulation In Clostridioides Difficile, Areej Malik, Adenrele Oludiran, Asia Poudel, Orlando Berumen Alvarez, Charles Woodward, Erin B. Purcell
Reiq-Mediated Alarmone Signalling Regulates Growth, Stress-Induced Biofilm Formation And Spore Accumulation In Clostridioides Difficile, Areej Malik, Adenrele Oludiran, Asia Poudel, Orlando Berumen Alvarez, Charles Woodward, Erin B. Purcell
Chemistry & Biochemistry Faculty Publications
The bacterial stringent response (SR) is a conserved transcriptional reprogramming pathway mediated by the nucleotide signalling alarmones, (pp)pGpp. The SR has been implicated in antibiotic survival in Clostridioides difficile, a biofilm- and spore-forming pathogen that causes resilient, highly recurrent C. difficile infections. The role of the SR in other processes and the effectors by which it regulates C. difficile physiology are unknown. C. difficile RelQ is a clostridial alarmone synthetase. Deletion of relQ dysregulates C. difficile growth in unstressed conditions, affects susceptibility to antibiotic and oxidative stressors and drastically reduces biofilm formation. While wild-type C. difficile displays increased biofilm …
Multiple Variables Influence The Finely Calibrated Antioxidant Defenses Of Clostridioides Difficile, Erin B. Purcell
Multiple Variables Influence The Finely Calibrated Antioxidant Defenses Of Clostridioides Difficile, Erin B. Purcell
Chemistry & Biochemistry Faculty Publications
The obligate anaerobe Clostridioides difficile encodes multiple reductases to detoxify molecular oxygen and reactive oxygen species. Caulat and colleagues have characterized the activity and regulation of four such reductases (L. C. Caulat, A. Lotoux, M. C. Martins, N. Kint, et al., mBio 15:e01591-24, 2024, https://doi.org/10.1128/mbio.01591-24). Each proved critical for clostridial survival in a different range of oxygen concentrations; together, they ameliorate a broad range of oxidative stress levels. Moreover, two previously uncharacterized regulators were found to control reductase gene expression in response to oxidative stress. The genetic repressor Rex and the reductase FdpF are both sensitive to the NAP …
Host-Defense Piscidin Peptides As Antibiotic Adjuvants Against Clostridioides Difficile, Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell
Host-Defense Piscidin Peptides As Antibiotic Adjuvants Against Clostridioides Difficile, Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell
Chemistry & Biochemistry Faculty Publications
The spore-forming intestinal pathogen Clostridioides difficile causes multidrug resistant infection with a high rate of recurrence after treatment. Piscidins 1 (p1) and 3 (p3), cationic host defense peptides with micromolar cytotoxicity against C. difficile, sensitize C. difficile to clinically relevant antibiotics tested at sublethal concentrations. Both peptides bind to Cu2+ using an amino terminal copper and nickel binding motif. Here, we investigate the two peptides in the apo and holo states as antibiotic adjuvants against an epidemic strain of C. difficile. We find that the presence of the peptides leads to lower doses of …
Expanding Our Grasp Of Two-Component Signaling In Clostridioides Difficile, Orlando Berumen Alvarez, Erin B. Purcell
Expanding Our Grasp Of Two-Component Signaling In Clostridioides Difficile, Orlando Berumen Alvarez, Erin B. Purcell
Chemistry & Biochemistry Faculty Publications
The intestinal pathogen Clostridioides difficile encodes roughly 50 TCS, but very few have been characterized in terms of their activating signals or their regulatory roles. A. G. Pannullo, B. R. Zbylicki, and C. D. Ellermeier (J Bacteriol 205:e00164-23, 2023, https://doi.org/10.1128/jb.00164-23) have identified both for the novel C. difficile TCD DraRS. DraRS responds to antibiotics that target lipid-II molecules in the bacterial cell envelope, and regulates the production of a novel glycolipid necessary for bacitracin and daptomycin resistance in C. difficile.
Size-Dependent Inhibitory Effects Of Antibiotic Drug Nanocarriers Against Pseudomonas Aeruginosa, Feng Ding, Preeyaporn Songkiatisak, Pavan Kumar Cherukuri, Tao Huang, Xiao-Hong Nancy Xu
Size-Dependent Inhibitory Effects Of Antibiotic Drug Nanocarriers Against Pseudomonas Aeruginosa, Feng Ding, Preeyaporn Songkiatisak, Pavan Kumar Cherukuri, Tao Huang, Xiao-Hong Nancy Xu
Chemistry & Biochemistry Faculty Publications
Multidrug membrane transporters (efflux pumps) are responsible for multidrug resistance (MDR) and the low efficacy of therapeutic drugs. Noble metal nanoparticles (NPs) possess a high surface-area-to-volume ratio and size-dependent plasmonic optical properties, enabling them to serve both as imaging probes to study sized-dependent MDR and as potential drug carriers to circumvent MDR and enhance therapeutic efficacy. To this end, in this study, we synthesized three different sizes of silver nanoparticles (Ag NPs), 2.4 ± 0.7, 13.0 ± 3.1, and 92.6 ± 4.4 nm, functionalized their surface with a monolayer of 11-amino-1-undecanethiol (AUT), and covalently conjugated them with antibiotics (ofloxacin, Oflx) …