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ACS Infectious Diseases

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https://www.readbyqxmd.com/read/28933816/reborn-from-the-ashes-turning-organic-molecules-to-antimicrobial-carbon-quantum-dots
#1
Scott G Harroun, Jui-Yang Lai, Chih-Ching Huang, Shou-Kuan Tsai, Han-Jia Lin
Using polyamines as the initial organic raw material and by applying simple pyrolysis methods, super cationic carbon quantum dots (CQDs) can easily be made. Since polyamines are natural products and the synthesis procedure is green, these polyamine-derived CQDs display low toxicity and high biocompatibility but possess high antibacterial activity. In addition, polyamine-derived CQDs display other unique properties, such as facilitation of wound healing and passage through the tight junction, which make them a very promising bactericide in future clinical applications...
September 21, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28918638/a-rapid-blood-test-to-determine-the-active-status-and-duration-of-acute-viral-infection
#2
Tianyu Zheng, Caroline Finn, Christopher J Parrett, Kunal Dhume, Ji Hae Hwang, David Sidhom, Tara M Strutt, Yuen Yee Li Sip, Karl K McKinstry, Qun Huo
The ability to rapidly detect and diagnose acute viral infections is crucial for infectious disease control and management. Serology testing for the presence of virus-elicited antibodies in blood is one of the methods used commonly for clinical diagnosis of viral infections. However, standard serology-based tests have a significant limitation: they cannot easily distinguish active from past, historical infections. As a result, it is difficult to determine whether a patient is currently infected with a virus or not, and on an optimal course of action, based off of positive serology testing responses...
September 20, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28918634/engineered-probiotic-for-the-inhibition-of-salmonella-via-tetrathionate-induced-production-of-microcin-h47
#3
Jacob D Palmer, Emma Piattelli, Beth A McCormick, Mark W Silby, Christopher J Brigham, Vanni Bucci
Complications arising from antibiotic-resistant bacteria are becoming one of the key issues in modern medicine. Members of drug-resistant Enterobacteriaceae spp. include opportunistic pathogens (e.g., Salmonella spp.) that are among the leading causes of morbidity and mortality worldwide. Overgrowth of these bacteria is considered a hallmark of intestinal dysbiosis. Microcins (small antimicrobial peptides) produced by some gut commensals can potentially cure these conditions by inhibiting these pathogens and have been proposed as a viable alternative to antibiotic treatment...
September 20, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28927276/alkoxycarbonate-ester-prodrugs-of-preclinical-drug-candidate-elq-300-for-prophylaxis-and-treatment-of-malaria
#4
Lisa Frueh, Yuexin Li, Michael Mather, Qigui Li, Sovitj Pou, Aaron Nilsen, Rolf W Winter, Isaac Forquer, April Pershing, Lisa H Xie, Martin J Smilkstein, Diana Caridha, Robert F Campbell, Richard J Sciotti, Mara Kreishman-Deitrick, Jane X Kelly, Brian Andrew Vesely, Akhil Vaidya, Michael K Riscoe
ELQ-300 is a preclinical antimalarial drug candidate that is active against liver, blood, and transmission stages of Plasmodium falciparum. While ELQ-300 is highly effective when administered in a low multi-dose regimen, poor aqueous solubility and high crystallinity have hindered its clinical development. To overcome its challenging physiochemical properties, a number of bioreversible alkoxycarbonate ester prodrugs of ELQ-300 were synthesized. These bioreversible prodrugs are converted to ELQ-300 by host and parasite esterase action in the liver and bloodstream of the host...
September 19, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28862830/plasma-levels-of-complement-factor-i-and-c4b-peptides-are-associated-with-hiv-suppression
#5
Boyue Wu, Zhengyu Ouyang, Christopher J Lyon, Wei Zhang, Tori Clift, Christopher R Bone, Boan Li, Zhen Zhao, Jason T Kimata, Xu G Yu, Ye Hu
Individuals who exhibit long-term HIV suppression and CD4 T-cell preservation without antiretroviral therapy are of great interest for HIV research. There is currently no robust method for rapid identification of these "HIV controller" subjects; however, HLA-B*57 (human leukocyte antigen (major histocompatibility complex), class I, B*57) genotype exhibits modest sensitivity for this phenotype. Complement C3b and C4b can influence HIV infection and replication, but studies have not examined their possible link to HIV controller status...
September 15, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28870074/exhaled-volatile-organic-compounds-of-infection-a-systematic-review
#6
Waqar M Ahmed, Oluwasola Lawal, Tamara M Nijsen, Royston Goodacre, Stephen J Fowler
With heightened global concern of microbial drug resistance, advanced methods for early and accurate diagnosis of infection are urgently needed. Analysis of exhaled breath volatile organic compounds (VOCs) toward detecting microbial infection potentially allows a highly informative and noninvasive alternative to current genomics and culture-based methods. We performed a systematic review of research literature reporting human and animal exhaled breath VOCs related to microbial infections. In this Review, we find that a wide range of breath sampling and analysis methods are used by researchers, which significantly affects interstudy method comparability...
September 13, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28892353/the-next-wave-of-influenza-drugs
#7
Megan L Shaw
Options for influenza therapy are currently limited to one class of drug, the neuraminidase inhibitors. Amidst concerns about drug resistance, much effort has been placed on the discovery of new drugs with distinct targets and mechanisms of action, with great success. There are now several candidates in late stage development which include small molecules targeting the three subunits of the viral polymerase complex and monoclonal antibodies targeting the hemagglutinin, as well as host-directed therapies. The availability of drugs with diverse mechanisms now opens the door to exploring combination therapies for influenza, and the range of administration routes presents more opportunities for treating hospitalized patients...
September 11, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28889735/small-molecule-potentiators-for-conventional-antibiotics-against-staphylococcus-aureus
#8
Arno Vermote, Serge Van Calenbergh
Antimicrobial resistance constitutes a global health problem, while the discovery and development of novel antibiotics is stagnating. Methicillin-resistant Staphylococcus aureus, responsible for the establishment of recalcitrant, biofilm-related infections, is a well known and notorious example of a highly resistant micro organism. Since resistance development is unavoidable with conventional antibiotics that target bacterial viability, it is vital to develop alternative treatment options on top. Strategies aimed at more subtle manipulation of bacterial behavior have recently attracted attention...
September 11, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28885829/membrane-active-amphipathic-peptide-wrl3-with-in-vitro-antibiofilmcapability-and-in-vivo-efficacy-in-treating-mrsa-burn-wound-infections
#9
Zhi Ma, Jinzhi Han, Bingxue Chang, Ling Gao, Zhaoxin Lu, Fengxia Lu, Haizhen Zhao, Chong Zhang, Xiaomei Bie
Methicillin-resistant Staphylococcus aureus (MRSA) has become increasingly prevalent in hospitals, clinics, and the community. MRSA can cause significant and even lethal infections, especially in skin burn wounds. The currently available topical agents have largely failed to eliminate MRSA infections due to resistance. Therefore, there is an urgent need for new and effective approaches for treating MRSA. Here, we show that a novel engineered amphipathic peptide, WRL3, exhibits potent antimicrobial activity against MRSA, even in the presence of various salts or serum...
September 8, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28875696/surface-enhanced-raman-spectroscopy-based-sandwich-immunoassays-for-multiplexed-detection-of-zika-and-dengue-viral-biomarkers
#10
Maria Sánchez-Purrà, Marc Carré-Camps, Helena de Puig, Irene Bosch, Lee Gehrke, Kimberly Hamad-Schifferli
Zika and dengue are mosquito-borne diseases that present similar nonspecific symptoms but possess dramatically different outcomes. The first line of defense in epidemic outbreaks are rapid point-of-care diagnostics. Because many outbreaks occur in areas that are resource poor, assays that are easy to use, inexpensive, and require no power have become invaluable in patient treatment, quarantining, and surveillance. Paper-based sandwich immunoassays such as lateral flow assays (LFAs) are attractive as point-of-care solutions as they have the potential for wider deployability than lab-based assays such as PCR...
September 6, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28850209/hydrogen-sulfide-and-reactive-sulfur-species-impact-proteome-s-sulfhydration-and-global-virulence-regulation-in-staphylococcus-aureus
#11
Hui Peng, Yixiang Zhang, Lauren D Palmer, Thomas E Kehl-Fie, Eric P Skaar, Jonathan C Trinidad, David P Giedroc
Hydrogen sulfide (H2S) is thought to protect bacteria from oxidative stress, but a comprehensive understanding of its function in bacteria is largely unexplored. In this study, we show that the human pathogen Staphylococcus aureus (S. aureus) harbors significant effector molecules of H2S signaling, reactive sulfur species (RSS), as low molecular weight persulfides of bacillithiol, coenzyme A, and cysteine, and significant inorganic polysulfide species. We find that proteome S-sulfhydration, a post-translational modification (PTM) in H2S signaling, is widespread in S...
September 6, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28845973/human-microbiome-inspired-antibiotics-with-improved-%C3%AE-lactam-synergy-against-mdr-staphylococcus-aureus
#12
John Chu, Xavier Vila Farres, Daigo Inoyama, Ricardo Gallardo-Macias, Mark Jaskowski, Shruthi Satish, Joel Stephen Freundlich, Sean F Brady
The flippase MurJ is responsible for transporting the cell wall intermediate lipid II from the cytoplasm to the outside of the cell. While essential for the survival of bacteria it remains an underexploited target for antibacterial therapy. The humimycin antibiotics are lipid II flippase (MurJ) inhibitors that were synthesized based on bioinformatic predictions derived from secondary metabolite gene clusters found in the human microbiome. Here we describe an SAR campaign around humimycin A that produced humimycin 17S...
August 28, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28835096/reversibility-of-covalent-broad-spectrum-serine-%C3%AE-lactamase-inhibition-by-the-diazabicyclooctenone-etx2514
#13
Adam B Shapiro, Ning Gao, Haris Jahić, Nicole M Carter, April Chen, Alita A Miller
ETX2514 is a non-β-lactam serine β-lactamase inhibitor in clinical development that has greater potency and broader spectrum of β-lactamase inhibition than the related diazabicyclooctanone avibactam. Despite opening of its cyclic urea ring upon acylation, avibactam can recyclize and dissociate intact from certain β-lactamases. We investigated reversibility of ETX2514 acylation of 10 serine β-lactamases representing Ambler classes A, C, and D. Dissociation rate constants varied widely between enzymes and were lowest for class D...
August 28, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28820574/thiol-containing-metallo-%C3%AE-lactamase-inhibitors-resensitize-resistant-gram-negative-bacteria-to-meropenem
#14
Kamaleddin Haj Mohammad Ebrahim Tehrani, Nathaniel I Martin
The prevalence of infections caused by metallo-β-lactamase (MBL) expressing Gram-negative bacteria has grown at an alarming rate in recent years. Despite the fact that MBLs can deactivate virtually all β-lactam antibiotics, there are as of yet no approved drugs available that inhibit their activity. We here examine the ability of previously reported thiol-based MBL inhibitors to synergize with meropenem and cefoperazone against a panel of Gram-negative carbapenem-resistant isolates expressing different β-lactamases...
August 28, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28810737/identification-of-the-colicin-v-bacteriocin-gene-cluster-by-functional-screening-of-a-human-microbiome-metagenomic-library
#15
Louis J Cohen, Sun Han, Yun-Han Huang, Sean F Brady
The forces that shape human microbial ecology are complex. It is likely that human microbiota, similarly to other microbiomes, use antibiotics as one way to establish an ecological niche. In this study, we use functional metagenomics to identify human microbial gene clusters that encode for antibiotic functions. Screening of a metagenomic library prepared from a healthy patient stool sample led to the identification of a family of clones with inserts that are 99% identical to a region of a virulence plasmid found in avian pathogenic Escherichia coli...
August 21, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28758395/hydrophilic-phage-mimicking-membrane-active-antimicrobials-reveal-nanostructure-dependent-activity-and-selectivity
#16
Yunjiang Jiang, Wan Zheng, Liangju Kuang, Hairong Ma, Hongjun Liang
The prevalent wisdom on developing membrane active antimicrobials (MAAs) is to seek a delicate, yet unquantified, cationic-hydrophobic balance. Inspired by phages that use nanostructured protein devices to invade bacteria efficiently and selectively, we study here the antibiotic role of nanostructures by designing spherical and rod-like polymer molecular brushes (PMBs) that mimic the two basic structural motifs of bacteriophages. Three model PMBs with different well-defined geometries consisting of multiple, identical copies of densely packed poly(4-vinyl-N-methylpyridine iodide) branches are synthesized by controlled/"living" polymerization, reminiscent of the viral structural motifs comprised of multiple copies of protein subunits...
August 18, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28799332/attaching-the-nora-efflux-pump-inhibitor-inf55-to-methylene-blue-enhances-antimicrobial-photodynamic-inactivation-of-methicillin-resistant-staphylococcus-aureus-in-vitro-and-in-vivo
#17
Ardeshir Rineh, Naveen K Dolla, Anthony R Ball, Maria Magana, John B Bremner, Michael R Hamblin, George P Tegos, Michael J Kelso
Antimicrobial photodynamic inactivation (aPDI) uses photosensitizers (PSs) and harmless visible light to generate reactive oxygen species (ROS) and kill microbes. Multidrug efflux systems can moderate the phototoxic effects of PSs by expelling the compounds from cells. We hypothesized that increasing intracellular concentrations of PSs by inhibiting efflux with a covalently attached efflux pump inhibitor (EPI) would enhance bacterial cell phototoxicity and reduce exposure of neighboring host cells to damaging ROS...
August 17, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28812869/entry-inhibitors-a-perspective-for-prevention-of-hepatitis-c-virus-infection-in-organ-transplantation
#18
Che C Colpitts, Raymond T Chung, Thomas F Baumert
Entry inhibitors are emerging as an attractive class of therapeutics for hepatitis C virus (HCV) infection. Entry inhibitors target either virion-associated factors or cellular factors necessary for infection. By blocking entry into cells, entry inhibitors prevent both the establishment of persistent reservoirs and the emergence of resistant variants during viral replication. Furthermore, entry inhibitors protect naïve cells from virus-induced alterations. Combining entry inhibitors with direct-acting antivirals (DAAs) may therefore improve treatment outcomes, particularly in the context of organ transplantation...
August 16, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28756664/structural-and-functional-survey-of-environmental-aminoglycoside-acetyltransferases-reveals-functionality-of-resistance-enzymes
#19
Zhiyu Xu, Peter J Stogios, Andrew T Quaile, Kevin J Forsberg, Sanket Patel, Tatiana Skarina, Scott Houliston, Cheryl Arrowsmith, Gautam Dantas, Alexei Savchenko
Aminoglycoside N-acetyltransferases (AACs) confer resistance against the clinical use of aminoglycoside antibiotics. The origin of AACs can be traced to environmental microbial species representing a vast reservoir for new and emerging resistance enzymes, which are currently undercharacterized. Here, we performed detailed structural characterization and functional analyses of four metagenomic AAC (meta-AACs) enzymes recently identified in a survey of agricultural and grassland soil microbiomes ( Forsberg et al...
August 16, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28770988/teixobactin-and-its-analogues-a-new-hope-in-antibiotic-discovery
#20
William D Fiers, Mark Craighead, Ishwar Singh
Increasing bacterial resistance against current antibiotics and lack of new molecules to combat bacterial resistance are key challenges to global health. There is, therefore, a continuing need to develop new antibiotics. Teixobactin, a cyclic undecapeptide, displays excellent antibacterial activities against a range of pathogenic bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis. Interestingly, it operates by multiple modes of actions and is bactericidal toward S...
August 3, 2017: ACS Infectious Diseases
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