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Bacterial resistance

Geoff A Christensen, JiWon Moon, Allison M Veach, Jennifer J Mosher, Ann M Wymore, Joy D van Nostrand, Jizhong Zhou, Terry C Hazen, Adam P Arkin, Dwayne A Elias
Using in-field bioreactors, we investigated the influence of exogenous microorganisms in groundwater planktonic and biofilm microbial communities as part of the Integrated Field Research Challenge (IFRC). After an acclimation period with source groundwater, bioreactors received either filtered (0.22 μM filter) or unfiltered well groundwater in triplicate and communities were tracked routinely for 23 days after filtration was initiated. To address geochemical influences, the planktonic phase was assayed periodically for protein, organic acids, physico-/geochemical measurements and bacterial community (via 16S rRNA gene sequencing), while biofilms (i...
2018: PloS One
Malcolm Spain, Joseph K-H Wong, Gayathri Nagalingam, James M Batten, Elinor Hortle, Stefan Oehlers, Xiao Fan Jiang, Hasini E Murage, Jack T Orford, Patrick Crisologo, James A Triccas, Peter J Rutledge, Matthew H Todd
We recently reported the discovery of non-toxic cyclam-derived compounds that are active against drug-resistant Mycobacterium tuberculosis. In this paper we report exploration of the structure-activity relationship for this class of compounds, identifying several simpler compounds with comparable activity. The most promising compound identified, possessing significantly improved water solubility, displayed high levels of bacterial clearance in an in vivo zebrafish embryo model, suggesting this compound series has promise for in vivo treatment of tuberculosis...
March 20, 2018: Journal of Medicinal Chemistry
Jacqueline M Zaengle-Barone, Abigail C Jackson, David M Besse, Bradford Becken, Mehreen Arshad, Patrick C Seed, Katherine J Franz
The unabated rise in bacterial resistance to conventional antibiotics, coupled with collateral damage to normal flora incurred by overuse of broad-spectrum antibiotics, necessitates the development of new antimicrobials targeted against pathogenic organisms. Here, we explore the antibacterial outcomes and mode of action of a prochelator that exploits the production of β-lactamase enzymes by drug-resistant bacteria to convert a non-toxic compound into a metal-binding antimicrobial agent directly within the microenvironment of pathogenic organisms...
March 20, 2018: ACS Infectious Diseases
P Petkov, R Marinova, V Kochev, N Ilieva, E Lilkova, L Litov
Antimicrobial peptides (AMPs) play crucial role as mediators of the primary host defence against microbial invasion. They are considered a promising alternative to antibiotics for multidrug resistant bacterial strains. For complete understanding of the antimicrobial defence mechanism, a detailed knowledge of the dynamics of peptide-membrane interactions, including atomistic studies on AMPs geometry and both peptide and membrane structural changes during the whole process is a prerequisite. We aim at clarifying the conformation dynamics of small linear AMPs in solution as a first step of in silico protocol for establishing a correspondence between certain amino-acid sequence motifs, secondary-structure elements, conformational dynamics in solution and the intensity and mode of interaction with the bacterial membrane...
March 20, 2018: Journal of Biomolecular Structure & Dynamics
Elizabeth Ann Misch, Christopher Saddler, James Muse Davis
PURPOSE OF REVIEW: This review describes recent trends in the epidemiology of nontuberculous mycobacteria (NTM), emerging pathogens, new insights into NTM pathogenesis, and advances in diagnosis and treatment. RECENT FINDINGS: Emerging pathogens include Mycobacterium chimaera and drug-resistant subspecies of Mycobacterium abscessus. Important virulence mechanisms of pathogenic NTM include the ability to alter the macrophage's permissiveness to intracellular bacterial growth...
March 19, 2018: Current Infectious Disease Reports
Sheela Swamy, William Barcella, Maria De Iorio, Kiren Gill, Rajvinder Khasriya, Anthony S Kupelian, Jennifer L Rohn, James Malone-Lee
PURPOSE: Lower urinary tract symptoms (LUTS) may be associated with chronic urinary tract infection (UTI) undetected by routine diagnostic tests. Antimicrobial therapy might confer benefit for these patients. MATERIALS AND METHODS: Over 10 years, we treated patients with chronic LUTS. Pyuria was adopted as the principal biomarker of infection. Urinary leucocyte counts were recorded from microscopy of fresh midstream urine (MSU) samples. Antibiotics were prescribed and the prescription adjusted to achieve a measurable clinical response and a reduction in pyuria...
March 20, 2018: International Urogynecology Journal
Georgios D Kitsios
Severe bacterial pneumonia is a major global cause of morbidity and mortality, yet current diagnostic approaches rely on identification of causative pathogens by cultures, which require extended incubation periods and often fail to detect relevant pathogens. Consequently, patients are prescribed broad-spectrum antibiotics in a "one-size-fits-all" manner, which may be inappropriate for their individual needs and promote antibiotic resistance. My research focuses on leveraging next-generation sequencing of microbial DNA directly from patient samples for the development of new, culture-independent definitions of pneumonia...
March 2018: MSystems
Tang Gao, Hongliang Zeng, Huan Xu, Feng Gao, Wei Li, Shengwang Zhang, Yi Liu, Guifang Luo, Mingdan Li, Dejian Jiang, Zhigao Chen, Yong Wu, Wei Wang, Wenbin Zeng
Background: Increasing bacterial infections as well as a rise in bacterial resistance call for the development of novel and safe antimicrobial agents without inducing bacterial resistance. Nanoparticles (NPs) present some advantages in treating bacterial infections and provide an alternative strategy to discover new antibiotics. Here, we report the development of novel self-assembled fluorescent organic nanoparticles ( FONs ) with excellent antibacterial efficacy and good biocompatibility. Methods: Self-assembly of 1-(12-(pyridin-1-ium-1-yl)dodecyl)-4-(1,4,5-triphenyl-1H-imidazol-2-yl)pyridin-1-ium (TPIP) in aqueous solution was investigated using dynamic light scattering (DLS) and transmission electron microscopy (TEM)...
2018: Theranostics
Alex Echeverría-Vega, Guillermo Chong, Antonio E Serrano, Mariela Guajardo, Olga Encalada, Victor Parro, Yolanda Blanco, Luis Rivas, Kevin C Rose, Mercedes Moreno-Paz, José A Luque, Nathalie A Cabrol, Cecilia S Demergasso
Laguna Negra and Lo Encañado are two oligotrophic Andean lakes forming part of the system fed by meltwater from distinct glacial tongues of the Echaurren glacier in central Chile, which is in a recession period. The recent increase in temperature and decline in precipitation have led to an increase of glacial meltwater and sediments entering these lakes. Although the lacustrine systems are also hydrogeologically connected, the limnology of the lakes is strongly controlled by the surface processes related to the respective sub-watersheds and hydrology...
2018: Frontiers in Microbiology
Holly C May, Jieh-Juen Yu, M N Guentzel, James P Chambers, Andrew P Cap, Bernard P Arulanandam
As microbial resistance to drugs continues to rise at an alarming rate, finding new ways to combat pathogens is an issue of utmost importance. Development of novel and specific antimicrobial drugs is a time-consuming and expensive process. However, the re-purposing of previously tested and/or approved drugs could be a feasible way to circumvent this long and costly process. In this review, we evaluate the U.S. Food and Drug Administration tested drugs auranofin, ebselen, and PX-12 as antimicrobial agents targeting the thioredoxin system...
2018: Frontiers in Microbiology
Feng Yang, Yonggen Jiang, Lihua Yang, Juanxiu Qin, Mingquan Guo, Yuxia Lu, Hongyou Chen, Yuan Zhuang, Jinghao Zhang, Hong Zhang, Zhaoyun Dai, Min Li, Changqing Yang, Min Chen, Yanmei Zhang, Hu Zhao
Objective: To investigate prevalence of acute diarrhea in Shanghai and analyze virulence associated-genes and antibiotic resistance of major enteropathogens using combination of conventional and molecular epidemiology methods. Method: The 412 stool specimens were obtained by systematic sampling from diarrhea patients throughout entire year 2016. Bacterial and viral pathogens were identified and bacterial isolates were cultured and screened for antibiotic resistance profiles. Two most prevalent bacteria, Vibrio parahaemolyticus and Salmonella were further typed by multi-locus sequence typing (MLST) and analyzed for presence of virulence-associated genes...
2018: Frontiers in Microbiology
Anne E Clatworthy, Keith P Romano, Deborah T Hung
To date, antibiotics have been identified on the basis of their ability to kill bacteria or inhibit their growth rather than directly for their capacity to improve clinical outcomes of infected patients. Although historically successful, this approach has led to the development of an antibiotic armamentarium that suffers from a number of shortcomings, including the inevitable emergence of resistance and, in certain infections, suboptimal efficacy leading to long treatment durations, infection recurrence, or high mortality and morbidity rates despite apparent bacterial sterilization...
March 19, 2018: Nature Chemical Biology
Lisa Maier, Mihaela Pruteanu, Michael Kuhn, Georg Zeller, Anja Telzerow, Exene Erin Anderson, Ana Rita Brochado, Keith Conrad Fernandez, Hitomi Dose, Hirotada Mori, Kiran Raosaheb Patil, Peer Bork, Athanasios Typas
A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain in vitro. Particular classes, such as the chemically diverse antipsychotics, were overrepresented in this group...
March 19, 2018: Nature
Kelly M Storek, Marcy R Auerbach, Handuo Shi, Natalie K Garcia, Dawei Sun, Nicholas N Nickerson, Rajesh Vij, Zhonghua Lin, Nancy Chiang, Kellen Schneider, Aaron T Wecksler, Elizabeth Skippington, Gerald Nakamura, Dhaya Seshasayee, James T Koerber, Jian Payandeh, Peter A Smith, Steven T Rutherford
The folding and insertion of integral β-barrel membrane proteins into the outer membrane of Gram-negative bacteria is required for viability and bacterial pathogenesis. Unfortunately, the lack of selective and potent modulators to dissect β-barrel folding in vivo has hampered our understanding of this fundamental biological process. Here, we characterize a monoclonal antibody that selectively inhibits an essential component of the Escherichia coli β-barrel assembly machine, BamA. In the absence of complement or other immune factors, the unmodified antibody MAB1 demonstrates bactericidal activity against an E...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Juan F Aranda, Stefan Rathjen, Ludger Johannes, Carlos Fernández-Hernando
Retrograde transport (RT) allows cells the retrieval of receptors and other cellular cargoes to the Golgi contributing to the maintenance of cellular homeostasis. This transport route is also commonly used by several bacterial toxins to exert their deleterious actions on eukaryotic cells. While the retrograde transport process has been well characterized, the contribution of microRNAs (miRNAs) in regulating this cellular transport mechanism remains unknown. Here, we identified that the intronic miRNA family, miR-199a/b , coordinate genes regulating RT and endosome trafficking...
March 19, 2018: Molecular and Cellular Biology
Artemis Gogos, Juan Cristobal Jimenez, Jennifer C Chang, Reid V Wilkening, Michael J Federle
The Rgg2/3 quorum sensing (QS) system is conserved among all sequenced isolates of Group A Streptococcus (GAS, Streptococcus pyogenes ). The molecular architecture of the system consists of a transcriptional activator (Rgg2) and a transcriptional repressor (Rgg3) under the control of autoinducing peptide pheromones (SHP2 and SHP3). Activation of the Rgg2/3 pathway leads to increases in biofilm formation and resistance to the bactericidal effects of the host factor, lysozyme. In this work, we show that deletion of a small gene, Spy49_0414c , abolished both phenotypes in response to pheromone signaling...
March 19, 2018: Journal of Bacteriology
Francesca Forti, Dwayne R Roach, Marco Cafora, Maria E Pasini, David S Horner, Ersilia V Fiscarelli, Martina Rossitto, Lisa Cariani, Federica Briani, Laurent Debarbieux, Daniela Ghisotti
The alarming diffusion of multidrug resistant (MDR) bacterial strains requires investigations on non-antibiotic therapies. Amongst them, the use of bacteriophages (phages) as antimicrobial agents, namely phage therapy, is a promising treatment strategy with support by recent successful compassionate treatments in Europe and the U.S.A. In this work, we combined host range and genomic information to design a 6-phage cocktail killing several clinical strains of P. aeruginosa , including those collected from Italian cystic fibrosis (CF) patients, and analyzed the cocktail performance...
March 19, 2018: Antimicrobial Agents and Chemotherapy
Martin Lorenz Eisinger, Laiyin Nie, Aline Ricarda Dörrbaum, Julian David Langer, Hartmut Michel
Multidrug resistance (MDR) in bacterial pathogens has become a severe threat to public health. Membrane transporters of the multidrug and toxic compound extrusion (MATE) family contribute critically to MDR, making them promising drug targets. Despite recent advances, structures in different conformations and the mechanistic details of their antiport cycle are still elusive. Here we studied NorM_PS, a representative MATE transporter from Pseudomonas stutzeri, using biochemical assays in combination with hydrogen/deuterium exchange-mass spectrometry (HDX-MS)...
March 16, 2018: Journal of Molecular Biology
Hajime Kanamori, David J Weber, Maria F Gergen, Lauren M DiBiase, Emily E Sickbert-Bennett, William A Rutala
BACKGROUND: Single outbreaks have often been reported in health care settings, but the frequency of outbreaks at a hospital over time has not been described. We examined epidemiologic features of all health care-associated outbreak investigations at an academic hospital during a 5-year period. METHODS: Health care-associated outbreak investigations at an academic hospital (2012-2016) were retrospectively reviewed through data on comprehensive hospital-wide surveillance and pulsed-field gel electrophoresis (PFGE) analysis...
March 16, 2018: American Journal of Infection Control
Chin-Chuan Tsai, Chi-Shiuan Lin, Chun-Ru Hsu, Chiu-Ming Chang, I-Wei Chang, Li-Wei Lin, Chih-Hsin Hung, Jiun-Ling Wang
BACKGROUND: No animal model studies have been conducted in which the efficacy of herbal compounds has been tested against multidrug-resistant Acinetobacter baumannii infections. Very few antibiotics are available for the treatment of pulmonary infections caused by extensively drug-resistant Acinetobacter baumannii (XDRAB). To find alternative treatments, traditional Chinese herbs were screened for their antimicrobial potential. METHODS: The present study screened 30 herbs that are traditionally used in Taiwan and that are commonly prescribed for heat clearing and detoxification...
March 20, 2018: BMC Complementary and Alternative Medicine
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