Browsing by Subject "Antibiotic resistance"

Now showing 1 - 7 of 7
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    Antibiotic Susceptibility Profile for the US Neisseria meningitidis Urethritis Clade
    (Oxford University Press, 2022-12-12) Bazan, Jose A.; Tzeng, Yih-Ling; Bischof, Katarina M.; Satola, Sarah W.; Stephens, David S.; Edwards, Jennifer L.; Carter, Alexandria; Snyder, Brandon; Norris Turner, Abigail; Microbiology and Immunology, School of Medicine
    The US Neisseria meningitidis urethritis clade (US_NmUC) harbors gonococcal deoxyribonucleic acid alleles and causes gonorrhea-like urogenital tract disease. A large convenience sample of US_NmUC isolates (N = 122) collected between January 2015 and December 2019 in Columbus, Ohio demonstrated uniform susceptibility to antibiotics recommended for gonorrhea treatment and meningococcal chemoprophylaxis.
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    Effects of Therapeutic Antibiotic Exposure on the Oropharyngeal and Fecal Microbiota in Infants With Cystic Fibrosis
    (Wiley, 2025) Hayden, Hillary S.; Nelson, Maria T.; Ross, Sydney E.; Verster, Adrian J.; Bouzek, Drake C.; Eng, Alex; Waalkes, Adam; Penewit, Kelsi; Kopp, Benjamin T.; Siracusa, Christopher; Rock, Michael J.; Salipante, Stephen J.; Hoffman, Lucas R.; Sanders, Don B.; Pediatrics, School of Medicine
    Background: Systemic antibiotics can impact all microbes inhabiting patients, regardless of the intended target organism(s). We studied the simultaneous effects on respiratory and fecal microbiomes of β-lactam antibiotics administered for respiratory symptoms in infants with cystic fibrosis (IWCF). Objective: To compare the magnitude and duration of intended (respiratory) and unintended (fecal) antimicrobial action by analyzing oropharyngeal (OP) and fecal microbiota in IWCF. Design: Shotgun metagenomic sequencing and qPCR were performed on OP and fecal samples collected longitudinally from 14 IWCF (ages 1-17 months) during ("On Antibiotics") and after ("Off Antibiotics") β-lactam therapy, and from 5 IWCF (3-16 months) never treated with antibiotics. Results: Total bacterial loads (TBL) for On Antibiotics samples were lower than for both Never (OP and fecal) and Off Antibiotics samples (fecal only). α-diversities (within-sample) for OP On Antibiotics samples were lower than for Never and Off Antibiotics samples but did not differ between fecal sample groups. β-diversity (between-sample) differed between all OP sample groups and between fecal On and Never Antibiotics and Off and Never antibiotics samples; however, fecal On and Off Antibiotics sample β-diversities did not differ. Patterns of change in antibiotic resistance gene abundances reflected shifts in microbial community composition. Conclusions: β-lactam antibiotic exposure was followed by marked alterations in both OP and fecal microbiota. While microbiota appeared to rebound after treatment in both sample types, our results suggest that fecal microbiota recovered less than OP. The clinical consequences of these findings should be studied in IWCF and other populations frequently treated with antibiotics.
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    Ketoconazole Resistant Candida albicans is Sensitive to a Wireless Electroceutical Wound Care Dressing
    (Elsevier, 2021) Khona, Dolly K.; Roy, Sashwati; Ghatak, Subhadip; Huang, Kaixiang; Jagdale, Gargi; Baker, Lane A.; Sen, Chandan K.; Surgery, School of Medicine
    Wireless electroceutical dressing (WED) fabric kills bacteria and disrupts bacterial biofilm. This work tested, comparing with standard of care topical antibiotic ketoconazole, whether the weak electric field generated by WED is effective to manage infection caused by ketoconazole-resistant yeast Candida albicans. WED inhibited Candida albicans biofilm formation and planktonic growth. Unlike ketoconazole, WED inhibited yeast to hyphal transition and downregulated EAP1 curbing cell attachment. In response to WED-dependent down-regulation of biofilm-forming BRG1 and ROB1, BCR1 expression was markedly induced in what seems to be a futile compensatory response. WED induced NRG1 and TUP1, negative regulators of filamentation; it down-regulated EFG1, a positive regulator of hyphal pathway. Consistent with the anti-hyphal properties of WED, the expression of ALS3 and HWP1 were diminished. Ketoconazole failed to reproduce the effects of WED on NRG1, TUP1 and EFG1. WED blunted efflux pump activity; this effect was in direct contrast to that of ketoconazole. WED exposure compromised cellular metabolism. In the presence of ketoconazole, the effect was synergistic. Unlike ketoconazole, WED caused membrane depolarization, changes in cell wall composition and loss of membrane integrity. This work presents first evidence that weak electric field is useful in managing pathogens which are otherwise known to be antibiotic resistant.
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    New antibiotics targeting Gram-negative bacilli
    (Department of Medicine and Surgery, University of Salerno, 2025-03-01) Al-Tawfiq, Jaffar A.; Sah, Ranjit; Mehta, Rachana; Apostolopoulos, Vasso; Temsah, Mohamad-Hani; Eljaaly, Khalid; Medicine, School of Medicine
    Antimicrobial resistance (AMR) is an emerging global threat. It increases mortality and morbidity rates and places a heavy burden on healthcare systems. Healthcare professionals can address the increasing issue of AMR by advocating responsible antibiotic use and supporting the development of new medications. Despite the economic, logistic, and scientific challenges, it is reassuring that new agents continue to be developed. This review addresses new antibiotics in the pipeline. A review of the literature was conducted including Medline, and Clinicaltrials.org, for approved and in pipeline antibiotics in phase 3 or new drug applications (NDA). We found several new antibiotics and reviewed their current development status, mode of action, spectra of activity, and indications for which they have been approved. The included studies from phase 3 clinical trials were mainly utilized for the treatment of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and pneumonia acquired in healthcare settings. The availability of these agents is limited for high-priority organisms. The identified antibiotics were primarily based on previously known molecules or pre-existing antimicrobial agents. There is a limited number of antibiotics against high priority organisms. New antimicrobial agents targeting the top-priority organisms identified by the World Health Organization are urgently needed. However, some antibiotics target ESBL-producing Enterobacterales, carbapenem-resistant Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa.
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    Repurposing MALDI-TOF MS for effective antibiotic resistance screening in Staphylococcus epidermidis using machine learning
    (Springer Nature, 2024-10-15) Ren, Michael; Chen, Qiang; Zhang, Jing; Engineering Technology, Purdue School of Engineering and Technology
    The emergence of Staphylococcus epidermidis as a significant nosocomial pathogen necessitates advancements in more efficient antimicrobial resistance profiling. However, existing culture-based and PCR-based antimicrobial susceptibility testing methods are far too slow or costly. This study combines machine learning with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to develop predictive models for various antibiotics using a comprehensive dataset containing thousands of S. epidermidis isolates. Optimized machine learning models utilized feature selection and achieved high AUROC scores ranging from 0.80 to 0.95 while maintaining AUPRC scores up to 0.97. Shapley Additive exPlanations were employed to analyze relevant features and assess the significance of corresponding protein biomarkers while also verifying that predictive power was derived from the detection of proteins rather than noise. Antimicrobial resistance models were validated externally to evaluate model performance outside the original data collection site. The approaches and findings in this study demonstrate a significant advancement in rapid, cost-effective antimicrobial resistance profiling, offering a promising solution for improving treatments for nosocomial infections and being potentially applicable to other microbial pathogens in the future.
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    Total Synthesis of Xanthoangelol B and Its Various Fragments: Toward Inhibition of Virulence Factor Production of Staphylococcus aureus
    (American Chemical Society, 2018-12-13) Mizar, Pushpak; Arya, Rekha; Kim, Truc; Cha, Soyoung; Ryu, Kyoung-Seok; Yeo, Won-sik; Bae, Taeok; Kim, Dae Wook; Park, Ki Hun; Kim, Kyeong Kyu; Lee, Seung Seo; Microbiology and Immunology, School of Medicine
    As an alternative strategy to fight antibiotic resistance, two-component systems (TCSs) have emerged as novel targets. Among TCSs, master virulence regulators that control the expression of multiple virulence factors are considered as excellent antivirulence targets. In Staphylococcus aureus, virulence factor expression is tightly regulated by a few master regulators, including the SaeRS TCS. In this study, we used a SaeRS GFP-reporter system to screen natural compound inhibitors of SaeRS, and identified xanthoangelol B 1, a prenylated chalcone from Angelica keiskei as a hit. We have synthesized 1 and its derivative PM-56 and shown that 1 and PM-56 both had excellent inhibitory potency against the SaeRS TCS, as demonstrated by various in vitro and in vivo experiments. As a mode of action, 1 and PM-56 were shown to bind directly to SaeS and inhibit its histidine kinase activity, which suggests a possibility of a broad spectrum inhibitor of histidine kinases.
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    Unravelling the physiological roles of mazEF toxin–antitoxin system on clinical MRSA strain by CRISPR RNA-guided cytidine deaminase
    (Springer Nature, 2022-05-07) Jain, Sonia; Bhowmick, Arghya; Jeong, Bohyun; Bae, Taeok; Ghosh, Abhrajyoti; Microbiology and Immunology, School of Medicine
    Background: Curiosity on toxin-antitoxin modules has increased intensely over recent years as it is ubiquitously present in many bacterial genomes, including pathogens like Methicillin-resistant Staphylococcus aureus (MRSA). Several cellular functions of TA systems have been proposed however, their exact role in cellular physiology remains unresolved. Methods: This study aims to find out the impact of the mazEF toxin-antitoxin module on biofilm formation, pathogenesis, and antibiotic resistance in an isolated clinical ST239 MRSA strain, by constructing mazE and mazF mutants using CRISPR-cas9 base-editing plasmid (pnCasSA-BEC). Transcriptome analysis (RNA-seq) was performed for the mazE antitoxin mutant in order to identify the differentially regulated genes. The biofilm formation was also assessed for the mutant strains. Antibiogram profiling was carried out for both the generated mutants followed by murine experiment to determine the pathogenicity of the constructed strains. Results: For the first time our work showed, that MazF promotes cidA mediated cell death and lysis for biofilm formation without playing any significant role in host virulence as suggested by the murine experiment. Interestingly, the susceptibility to oxacillin, daptomycin and vancomycin was reduced significantly by the activated MazF toxin in the mazE mutant strain. Conclusions: Our study reveals that activated MazF toxin leads to resistance to antibiotics like oxacillin, daptomycin and vancomycin. Therefore, in the future, any potential antibacterial drug can be designed to target MazF toxin against the problematic multi-drug resistant bug.