المؤلفون: Ngo, Thuan-Ethan, Ecker, Andrew, Ryu, Byeol, Guild, Aurora, Remmel, Ariana, Boudreau, Paul D, Alexander, Kelsey L, Naman, C Benjamin, Glukhov, Evgenia, Avalon, Nicole E, Shende, Vikram V, Thomas, Lamar, Dahesh, Samira, Nizet, Victor, Gerwick, Lena, Gerwick, William H

المصدر: ACS Chemical Biology. 19(3)

مصطلحات موضوعية: Microbiology, Biological Sciences, Genetics, Human Genome, Infectious Diseases, Candida albicans, Coculture Techniques, Cyanobacteria, Depsipeptides, Multigene Family, Chemical Sciences, Organic Chemistry, Biological sciences, Chemical sciences

الوصف: The tropical marine cyanobacterium Moorena producens JHB is a prolific source of secondary metabolites with potential biomedical utility. Previous studies on this strain led to the discovery of several novel compounds such as hectochlorins and jamaicamides. However, bioinformatic analyses of its genome indicate the presence of numerous cryptic biosynthetic gene clusters that have yet to be characterized. To potentially stimulate the production of novel compounds from this strain, it was cocultured with Candida albicans. From this experiment, we observed the increased production of a new compound that we characterize here as hectoramide B. Bioinformatic analysis of the M. producens JHB genome enabled the identification of a putative biosynthetic gene cluster responsible for hectoramide B biosynthesis. This work demonstrates that coculture competition experiments can be a valuable method to facilitate the discovery of novel natural products from cyanobacteria.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9qp2375sTest

المؤلفون: Siew, Ruth, Ou, Tzung-Lin, Dahesh, Samira, Akong, Kathryn, Nizet, Victor

المصدر: Infectious Microbes & Diseases. 4(3)

مصطلحات موضوعية: Medical Physiology, Biomedical and Clinical Sciences, Lung, Cystic Fibrosis, Rare Diseases, Clinical Research, Congenital, Good Health and Well Being, cystic fibrosis, bicarbonate, mucus, pneumonia, bacterial infection, neutrophil, cathelicidin, neutrophil extracellular traps

الوصف: The primary defect in cystic fibrosis (CF) is abnormal chloride and bicarbonate transport in the cystic fibrosis transmembrane conductance regulator (CFTR) epithelial ion channel. The apical surface of the respiratory tract is lined by an airway surface liquid layer (ASL) composed of mucin comprising mainly MUC5A and MUC5B glycoproteins. ASL homeostasis depends on sodium bicarbonate secretion into the airways and secretion deficits alter mucus properties leading to airway obstruction, inflammation, and infections. Downstream effects of abnormal ion transport in the lungs include altered intrinsic immune defenses. We observed that neutrophils killed Pseudomonas aeruginosa more efficiently when it had been exposed to sodium bicarbonate, and formation of neutrophil extracellular traps (NETs) by neutrophils was augmented in the presence of increasing bicarbonate concentrations. Physiological levels of bicarbonate sensitized P. aeruginosa to the antimicrobial peptide cathelicidin LL-37, which is present in both lung ASL and in NETs. Sodium bicarbonate has various uses in clinical medicine and in the care of CF patients, and could be further explored as a therapeutic adjunct against Pseudomonas infections.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6p40x3bfTest

المؤلفون: Rajput, Akanksha, Poudel, Saugat, Tsunemoto, Hannah, Meehan, Michael, Szubin, Richard, Olson, Connor A, Seif, Yara, Lamsa, Anne, Dillon, Nicholas, Vrbanac, Alison, Sugie, Joseph, Dahesh, Samira, Monk, Jonathan M, Dorrestein, Pieter C, Knight, Rob, Pogliano, Joe, Nizet, Victor, Feist, Adam M, Palsson, Bernhard O

المصدر: GigaScience. 10(1)

مصطلحات موضوعية: Antimicrobial Resistance, Prevention, Emerging Infectious Diseases, Infectious Diseases, Infection, Delivery of Health Care, Humans, Methicillin-Resistant Staphylococcus aureus, Microbial Sensitivity Tests, Staphylococcal Infections, Vancomycin

الوصف: The evolving antibiotic-resistant behavior of health care-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) USA100 strains are of major concern. They are resistant to a broad class of antibiotics such as macrolides, aminoglycosides, fluoroquinolones, and many more. The selection of appropriate antibiotic susceptibility examination media is very important. Thus, we use bacteriological (cation-adjusted Mueller-Hinton broth) as well as physiological (R10LB) media to determine the effect of vancomycin on USA100 strains. The study includes the profiling behavior of HA-MRSA USA100 D592 and D712 strains in the presence of vancomycin through various high-throughput assays. The US100 D592 and D712 strains were characterized at sub-inhibitory concentrations through growth curves, RNA sequencing, bacterial cytological profiling, and exo-metabolomics high throughput experiments. The study reveals the vancomycin resistance behavior of HA-MRSA USA100 strains in dual media conditions using wide-ranging experiments.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7fm6w9gtTest

المؤلفون: Salazar, Michael J, Machado, Henrique, Dillon, Nicholas A, Tsunemoto, Hannah, Szubin, Richard, Dahesh, Samira, Pogliano, Joseph, Sakoulas, George, Palsson, Bernhard O, Nizet, Victor, Feist, Adam M

المصدر: mSystems. 5(2)

مصطلحات موضوعية: Infectious Diseases, Biodefense, Antimicrobial Resistance, Prevention, Vaccine Related, Genetics, Emerging Infectious Diseases, 2.2 Factors relating to the physical environment, Aetiology, Infection, Staphylococcus aureus, antibiotic resistance, nafcillin, USA300, adaptive laboratory evolution, drug resistance mechanisms, Staphylococcus aureus

الوصف: Antimicrobial susceptibility testing standards driving clinical decision-making have centered around the use of cation-adjusted Mueller-Hinton broth (CA-MHB) as the medium with the notion of supporting bacterial growth, without consideration of recapitulating the in vivo environment. However, it is increasingly recognized that various medium conditions have tremendous influence on antimicrobial activity, which in turn may have major implications on the ability of in vitro susceptibility assays to predict antibiotic activity in vivo. To elucidate differential growth optimization and antibiotic resistance mechanisms, adaptive laboratory evolution was performed in the presence or absence of the antibiotic nafcillin with methicillin-resistant Staphylococcus aureus (MRSA) TCH1516 in either (i) CA-MHB, a traditional bacteriological nutritionally rich medium, or (ii) Roswell Park Memorial Institute (RPMI), a medium more reflective of the in vivo host environment. Medium adaptation analysis showed an increase in growth rate in RPMI, but not CA-MHB, with mutations in apt, adenine phosphoribosyltransferase, and the manganese transporter subunit, mntA, occurring reproducibly in parallel replicate evolutions. The medium-adapted strains showed no virulence attenuation. Continuous exposure of medium-adapted strains to increasing concentrations of nafcillin led to medium-specific evolutionary strategies. Key reproducibly occurring mutations were specific for nafcillin adaptation in each medium type and did not confer resistance in the other medium environment. Only the vraRST operon, a regulator of membrane- and cell wall-related genes, showed mutations in both CA-MHB- and RPMI-evolved strains. Collectively, these results demonstrate the medium-specific genetic adaptive responses of MRSA and establish adaptive laboratory evolution as a platform to study clinically relevant resistance mechanisms.IMPORTANCE The ability of pathogens such as Staphylococcus aureus to evolve resistance to antibiotics used in the treatment of infections has been an important concern in the last decades. Resistant acquisition usually translates into treatment failure and puts patients at risk of unfavorable outcomes. Furthermore, the laboratory testing of antibiotic resistance does not account for the different environment the bacteria experiences within the human body, leading to results that do not translate into the clinic. In this study, we forced methicillin-resistant S. aureus to develop nafcillin resistance in two different environments, a laboratory environment and a physiologically more relevant environment. This allowed us to identify genetic changes that led to nafcillin resistance under both conditions. We concluded that not only does the environment dictate the evolutionary strategy of S. aureus to nafcillin but also that the evolutionary strategy is specific to that given environment.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8c50p3jbTest

المؤلفون: Rajput, Akanksha, Poudel, Saugat, Tsunemoto, Hannah, Meehan, Michael, Szubin, Richard, Olson, Connor A, Lamsa, Anne, Seif, Yara, Dillon, Nicholas, Vrbanac, Alison, Sugie, Joseph, Dahesh, Samira, Monk, Jonathan M, Dorrestein, Pieter C, Knight, Rob, Nizet, Victor, Palsson, Bernhard O, Feist, Adam M, Pogliano, Joe

المصدر: Scientific data. 6(1)

مصطلحات موضوعية: Nafcillin, Culture Media, Sequence Analysis, RNA, Drug Resistance, Multiple, Bacterial, Metabolomics, Methicillin-Resistant Staphylococcus aureus, High-Throughput Screening Assays, Antimicrobial Resistance, Infectious Diseases, Prevention, Emerging Infectious Diseases, Infection

الوصف: Staphylococcus aureus strains have been continuously evolving resistance to numerous classes of antibiotics including methicillin, vancomycin, daptomycin and linezolid, compounding the enormous healthcare and economic burden of the pathogen. Cation-adjusted Mueller-Hinton broth (CA-MHB) is the standard bacteriological media for measuring antibiotic susceptibility in the clinical lab, but the use of media that more closely mimic the physiological state of the patient, e.g. mammalian tissue culture media, can in certain circumstances reveal antibiotic activities that may be more predictive of effectiveness in vivo. In the current study, we use both types of media to explore antibiotic resistance phenomena in hospital-acquired USA100 lineage methicillin-resistant, vancomycin-intermediate Staphylococcus aureus (MRSA/VISA) strain D712 via multidimensional high throughput analysis of growth rates, bacterial cytological profiling, RNA sequencing, and exo-metabolomics (HPLC and LC-MS). Here, we share data generated from these assays to shed light on the antibiotic resistance behavior of MRSA/VISA D712 in both bacteriological and physiological media.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5sd60373Test

المؤلفون: Dahesh, Samira, Wong, Brian, Nizet, Victor, Sakoulas, George, Tran, Truc T, Aitken, Samuel L

المصدر: Antimicrobial Agents and Chemotherapy. 63(7)

مصطلحات موضوعية: Antimicrobial Resistance, Infectious Diseases, Ampicillin, Anti-Bacterial Agents, Drug Resistance, Multiple, Bacterial, Drug Synergism, Enterococcus faecium, Gram-Positive Bacterial Infections, Humans, Lipoglycopeptides, Male, Microbial Sensitivity Tests, Middle Aged, Osteomyelitis, Vancomycin, Vancomycin-Resistant Enterococci, ampicillin, oritavancin, vancomycin-resistant Enterococcus faecium, vancomycin-resistant Enterococcus faecium, Microbiology, Medical Microbiology, Pharmacology and Pharmaceutical Sciences

الوصف: Weekly oritavancin plus ampicillin continuous infusion combination therapy was used to successfully treat a deep spine vancomycin-resistant Enterococcus faecium infection associated with hardware. Checkerboard and time-kill assays confirmed synergy between these two antibiotics. Further synergies of oritavancin and ampicillin with rifampin or the endogenous human antimicrobial peptide cathelicidin LL-37 were demonstrated.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/29c791whTest

المؤلفون: Poudel, Saugat, Tsunemoto, Hannah, Meehan, Michael, Szubin, Richard, Olson, Connor A, Lamsa, Anne, Seif, Yara, Dillon, Nicholas, Vrbanac, Alison, Sugie, Joseph, Dahesh, Samira, Monk, Jonathan M, Dorrestein, Pieter C, Pogliano, Joseph, Knight, Rob, Nizet, Victor, Palsson, Bernhard O, Feist, Adam M

المصدر: Scientific data. 6(1)

مصطلحات موضوعية: Nafcillin, Anti-Bacterial Agents, Culture Media, Bacteriological Techniques, Microbial Sensitivity Tests, Methicillin-Resistant Staphylococcus aureus, Transcriptome, Emerging Infectious Diseases, Infectious Diseases, Antimicrobial Resistance, Prevention, Infection

الوصف: Cation adjusted-Mueller Hinton Broth (CA-MHB) is the standard bacteriological medium utilized in the clinic for the determination of antibiotic susceptibility. However, a growing number of literature has demonstrated that media conditions can cause a substantial difference in the efficacy of antibiotics and antimicrobials. Recent studies have also shown that minimum inhibitory concentration (MIC) tests performed in standard cell culture media (e.g. RPMI and DMEM) are more indicative of in vivo antibiotic efficacy, presumably because they are a better proxy for the human host's physiological conditions. The basis for the bacterial media dependent susceptibility to antibiotics remains undefined. To address this question, we characterized the physiological response of methicillin-resistant Staphylococcus aureus (MRSA) during exposure to sub-inhibitory concentrations of the beta-lactam antibiotic nafcillin in either CA-MHB or RPMI + 10% LB (R10LB). Here, we present high quality transcriptomic, exo-metabolomic and morphological data paired with growth and susceptibility results for MRSA cultured in either standard bacteriologic or more physiologic relevant medium.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1h78q2k6Test

المؤلفون: Choe, Donghui, Szubin, Richard, Dahesh, Samira, Cho, Suhyung, Nizet, Victor, Palsson, Bernhard, Cho, Byung-Kwan

المصدر: Scientific reports. 8(1)

مصطلحات موضوعية: Virulence Factors, Gene Expression Profiling, Drug Resistance, Bacterial, Gene Expression Regulation, Bacterial, Transcription Initiation Site, Regulon, Gene Regulatory Networks, Promoter Regions, Genetic, Methicillin-Resistant Staphylococcus aureus, Prevention, Genetics, Human Genome, Emerging Infectious Diseases, Antimicrobial Resistance, Biodefense, Biotechnology, Vaccine Related, Infectious Diseases, 2.2 Factors relating to the physical environment, Infection

الوصف: Staphylococcus aureus infection is a rising public health care threat. S. aureus is believed to have elaborate regulatory networks that orchestrate its virulence. Despite its importance, the systematic understanding of the transcriptional landscape of S. aureus is limited. Here, we describe the primary transcriptome landscape of an epidemic USA300 isolate of community-acquired methicillin-resistant S. aureus. We experimentally determined 1,861 transcription start sites with their principal promoter elements, including well-conserved -35 and -10 elements and weakly conserved -16 element and 5' untranslated regions containing AG-rich Shine-Dalgarno sequence. In addition, we identified 225 genes whose transcription was initiated from multiple transcription start sites, suggesting potential regulatory functions at transcription level. Along with the transcription unit architecture derived by integrating the primary transcriptome analysis with operon prediction, the measurement of differential gene expression revealed the regulatory framework of the virulence regulator Agr, the SarA-family transcriptional regulators, and β-lactam resistance regulators. Interestingly, we observed a complex interplay between virulence regulation, β-lactam resistance, and metabolism, suggesting a possible tradeoff between pathogenesis and drug resistance in the USA300 strain. Our results provide platform resource for the location of transcription initiation and an in-depth understanding of transcriptional regulation of pathogenesis, virulence, and antibiotic resistance in S. aureus.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4b3062f7Test

المؤلفون: Pashangeh, Safoora, Shekarforoush, Seyed Shahram, Aminlari, Mahmoud, Hosseinzadeh, Saeid, Nizet, Victor, Dahesh, Samira, Rahmdel, Samane

المساهمون: Ministry of Science Research and Technology

المصدر: Food Science & Nutrition ; volume 10, issue 2, page 354-362 ; ISSN 2048-7177 2048-7177

الوصف: Histamine is an active amine compound that occurs in various fermented foods that may cause adverse effects on the human health. Certain microorganisms are able to degrade histamine by an oxidative deamination reaction. Therefore, the present study aimed to quantify histamine‐forming and/or ‐degrading activity of the isolates derived from milk of goat and sheep herds, in Iran, by the capillary zone electrophoresis (CZE) method; and we evaluated the molecular characteristics of staphylococcal isolates. Among 243 staphylococcal isolates, 29 histamine‐degrading bacteria were identified. One of these isolates, identified as Staph. epidermidis , No. 605, exhibited the highest activity compared to others, degrading available histamine to 58.33% within 24 h. By polymerase chain reaction (PCR) analysis, the isolate, No. 605 that exhibited remarkable histamine‐degrading activity lacked the genes encoding coagulase and DNase, nor did it harbor any of the five classical enterotoxin genes. This is the first report to show that seven Staphylococcus species, including Staph. chromogenes , Staph. aureus , Staph. haemolyticus , Staph. epidermidis , Staph . pseudintermedius , Staph . agnetis , and Staph. hyicus , were able to degrade histamine, which were hitherto not known to have this capacity. Therefore, histamine‐degrading activity is a definite criterion to introduce fermenting organisms able to decrease histamine content in different food products.

الإتاحة: https://doi.org/10.1002/fsn3.2723Test

المؤلفون: Hollands, Andrew, Corriden, Ross, Gysler, Gabriela, Dahesh, Samira, Olson, Joshua, Raza Ali, Syed, Kunkel, Maya T, Lin, Ann E, Forli, Stefano, Newton, Alexandra C, Kumar, Geetha B, Nair, Bipin G, Perry, J Jefferson P, Nizet, Victor

المصدر: The Journal of biological chemistry. 291(27)

مصطلحات موضوعية: Neutrophils, Humans, Anacardium, Sphingosine, Anacardic Acids, Lysophospholipids, Anti-Bacterial Agents, Respiratory Burst, Extracellular Traps, Anacardic Acid, Neutrophil extracellular traps, PI3 kinase, antibiotic resistance, innate immunity, neutrophil, reactive oxygen species, sphingosine-1-phosphate, Infectious Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Infection, Good Health and Well Being, Chemical Sciences, Biological Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology

الوصف: Emerging antibiotic resistance among pathogenic bacteria is an issue of great clinical importance, and new approaches to therapy are urgently needed. Anacardic acid, the primary active component of cashew nut shell extract, is a natural product used in the treatment of a variety of medical conditions, including infectious abscesses. Here, we investigate the effects of this natural product on the function of human neutrophils. We find that anacardic acid stimulates the production of reactive oxygen species and neutrophil extracellular traps, two mechanisms utilized by neutrophils to kill invading bacteria. Molecular modeling and pharmacological inhibitor studies suggest anacardic acid stimulation of neutrophils occurs in a PI3K-dependent manner through activation of surface-expressed G protein-coupled sphingosine-1-phosphate receptors. Neutrophil extracellular traps produced in response to anacardic acid are bactericidal and complement select direct antimicrobial activities of the compound.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5nz7p9qmTest