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bacterial drug resistance

Bing Cao, Fengfeng Xiao, Da Xing, Xianglong Hu
The increased threat of antibiotic resistance has created an urgent need for new strategies. Herein, polyprodrug antimicrobials are proposed to mimic antimicrobial peptides appended with a concurrent drug release property, exhibiting broad-spectrum antibacterial activity and especially high potency to inhibit methicillin-resistant Staphylococcus aureus (MRSA) without inducing resistance. Two series of polyprodrug antimicrobials are fabricated by facile polymerization of triclosan prodrug monomer (TMA) and subsequent quaternization of hydrophilic poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA), affording PDMAEMA-b-PTMA and PQDMA-b-PTMA, respectively...
August 17, 2018: Small
J Campanini-Salinas, J Andrades-Lagos, J Mella-Raipan, D Vasquez-Velasquez
Bacterial resistance is a growing problem worldwide and is estimated that deaths by infectious diseases associated with resistant pathogens will generate 10 million deaths per year in 2050. This problem becomes more serious due to the low level of research and development of new drugs, which has fallen drastically in the last 40 years. For example, in the last decade of a total of 293 new drugs approved by FDA, only 9 corresponded to antimicrobial drugs and none constituted a new structural class. The majority of the molecules in the clinical phase II or III, coming from modifications of drugs in clinical use, this strategy make easier the bacterial susceptibility to generate resistance through the mechanisms expressed for their drug predecessors...
August 16, 2018: Current Topics in Medicinal Chemistry
Yong-Xin Li, Zheng Zhong, Wei-Peng Zhang, Pei-Yuan Qian
The worldwide prevalence of infections caused by antibiotic-resistant Gram-negative bacteria poses a serious threat to public health due to the limited therapeutic alternatives. Cationic peptides represent a large family of antibiotics and have attracted interest due to their diverse chemical structures and potential for combating drug-resistant Gram-negative pathogens. Here, we analyze 7395 bacterial genomes to investigate their capacity for biosynthesis of cationic nonribosomal peptides with activity against Gram-negative bacteria...
August 16, 2018: Nature Communications
Mohit Yadav, Jitendra Singh Rathore
Here we report the first essentially complete TAome analysis for type II toxin-antitoxin (TA) system, a major class of TA modules found in bacterial system, from entomopathogenic bacterium Xenorhabdus nematophila ATCC 19061 (NCBI RefSeq NC_014228). We summarize this analysis in terms of TA locus, accession identifier, hits in conserved domain database, toxin superfamily, antitoxin superfamily and chromosomal/mobile genome/plasmid occurrences. Moreover, for TA context analyses we use six different specifications namely virulence factors, mobile genetic elements (MGE), antibiotic resistance genes, secretion systems, prophage and a classification of mobile genetic elements (ACLAME); among these hits are found for only MGE, ACLAME and prophage...
July 11, 2018: Computational Biology and Chemistry
Bimal Koirala, Robert A Hillman, Erin K Tiwold, Michael A Bertucci, Yftah Tal-Gan
Quorum sensing (QS) is a cell-cell communication mechanism that enables bacteria to assess their population density and alter their behavior upon reaching high cell number. Many bacterial pathogens utilize QS to initiate an attack on their host, thus QS has attracted significant attention as a potential antivirulence alternative to traditional antibiotics. Streptococcus pneumoniae , a notorious human pathogen responsible for a variety of acute and chronic infections, utilizes the competence regulon and its associated signaling peptide, the competence stimulating peptide (CSP), to acquire antibiotic resistance and establish an infection...
2018: Beilstein Journal of Organic Chemistry
Davide Carta, Paola Brun, Matteo Dal Pra, Giulia Bernabè, Ignazio Castagliuolo, Maria Grazia Ferlin
Our aim was to identify new multi-target compounds endowed with both anti-inflammatory and anti-bacterial activities for treatment of human infections. Diflunisal, a nonsteroidal anti-inflammatory agent, has recently been repurposed for its anti-virulence properties against methicillin-resistant Staphylococcus aureus . Effective synthesis of some aza-analogs of the anti-inflammatory drug diflunisal was carried out following the route involving key oxazole intermediates to obtain o - and m -hydroxypyridinecarboxylic acid derivatives...
June 1, 2018: MedChemComm
Kartsev Victor, Lichitsky Boris, Geronikaki Athina, Petrou Anthi, Smiljkovic Marija, Kostic Marina, Radanovic Oliver, Soković Marina
Usnic acid, a dibenzofuran, was originally isolated from lichens producing secondary metabolites, and is well known as an antibiotic, but is also endowed with several other interesting properties. Thus, the goal of this paper is the design of new usnic acid derivatives and evaluation of their antimicrobial activity. All newly synthesized compounds possess good antibacterial activity with MIC ranging from 1.02-50.93 × 10-2 mmol mL-1 and MBC from 2.05-70.57 × 10-2 mmol mL-1 . The most sensitive bacterial species was Staphylococcus aureus , while Pseudomonas aeruginosa and Escherichia coli were the most resistant among the ATCC strains, and MRSA was the most resistant among all tested bacteria (ATCC and clinical isolates)...
May 1, 2018: MedChemComm
Hatsuo Yamamura, Miho Nonaka, Shingo Okuno, Ryogo Mitsuhashi, Hisato Kato, Takashi Katsu, Kazufumi Masuda, Koichi Tanimoto, Haruyoshi Tomita, Atsushi Miyagawa
The emergence of drug-resistant bacteria has led to the high demand for new antibiotics. In this report, we investigated membrane-active antimicrobial β-cyclodextrins. These contain seven amino-modified alkyl groups on a molecule, which act as functional moieties to permeabilize bacterial cell membranes. The polyfunctionalization of cyclodextrins was achieved through a click reaction assisted by microwave irradiation. A survey using derivatives with systematically varied functionalities clarified the unique correlation of the antimicrobial activity of these compounds with their molecular structure and hydrophobicity/hydrophilicity balances...
March 1, 2018: MedChemComm
Maria Fesatidou, Panagiotis Zagaliotis, Charalampos Camoutsis, Anthi Petrou, Phaedra Eleftheriou, Christophe Tratrat, Micheline Haroun, Athina Geronikaki, Ana Ciric, Marina Sokovic
In continuation of our efforts to develop new compounds with antimicrobial properties we describe design, synthesis, molecular docking study and evaluation of antimicrobial activity of seventeen novel 2-{[5-(adamantan-1-yl)-1,3,4-thiadiazol-2-yl]-imino}-5-arylidene-1,3-thiazolidin-4-ones. All compounds showed antibacterial activity against eight Gram positive and Gram negative bacterial species. Twelve out of seventeen compounds were more potent than streptomycin and all compounds exhibited higher potency than ampicillin...
August 3, 2018: Bioorganic & Medicinal Chemistry
Eva Pericolini, Bruna Colombari, Gianmarco Ferretti, Ramona Iseppi, Andrea Ardizzoni, Massimo Girardis, Arianna Sala, Samuele Peppoloni, Elisabetta Blasi
BACKGROUND: Pseudomonas aeruginosa is an opportunistic bacterial pathogen responsible for both acute and chronic infections in humans. In particular, its ability to form biofilm, on biotic and abiotic surfaces, makes it particularly resistant to host's immune defenses and current antibiotic therapies as well. Innovative antimicrobial materials, like hydrogel, silver salts or nanoparticles have been used to cover new generation catheters with promising results. Nevertheless, biofilm remains a major health problem...
August 14, 2018: BMC Microbiology
Anna Stjärne Aspelund, Helena Hammarström, Malin Inghammar, Hillevi Larsson, Lennart Hansson, Gerdt C Riise, Vanda Friman, Bertil Christensson, Lisa I Påhlman
BACKGROUND: Lung transplant patients experience a high risk of airway infections and microbial colonization of the lung due to constant exposure to the environment through inhaled microorganisms, denervation, reduced ciliary transport and decreased cough. METHODS: In this nationwide prospective study on Swedish lung transplant patients, we evaluated the microbiological panorama of bacteria, fungi and virus found in bronchoalveolar lavage fluid (BALF) performed the first year after lung transplantation (LTx)...
August 14, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Maria D'Accolti, Irene Soffritti, Micol Piffanelli, Matteo Bisi, Sante Mazzacane, Elisabetta Caselli
Purpose: Many hospital-acquired infections (HAIs) can be transmitted by pathogens contaminating hospital surfaces, not efficiently controlled by conventional sanitation, which can indeed contribute to the selection of MDR strains. Bacteriophages have been suggested as decontaminating agents, based on their selective ability to kill specific bacteria. However, there are no data on their stability in detergents and their potential use in routine sanitation. On the other hand, a probiotic-based sanitation system (Probiotic Cleaning Hygiene System, PCHS) was recently shown to stably reduce pathogens on treated surfaces...
2018: Infection and Drug Resistance
Leila Rezaei Somee, Parinaz Ghadam, Ahya Abdi-Ali, Soudabeh Fallah, Ghodratollah Panahi
Silver nanoparticles (AgNPs) have attracted the attention of researchers due to their properties. Biological synthesis of AgNPs is eco-friendly and cost-effective preferred to physical and chemical methods, which utilize environmentally harmful agents and large amounts of energy. Microorganisms have been explored as potential biofactories to synthesize AgNPs. Bacterial NP synthesis is affected by Ag salt concentration, pH, temperature and bacterial species. In this study, Bacillus spp., isolated from soil, were screened for AgNP synthesis at pH 12 with 5 mM Ag nitrate (AgNO3 ) final concentration at room temperature...
September 2018: IET Nanobiotechnology
Mary Kate Alexander, Anh Miu, Angela Oh, Mike Reichelt, Hoangdung Ho, Cecile Chalouni, Sharada Labadie, Lan Wang, Jun Liang, Nicholas N Nickerson, Huiyong Hu, Lan Yu, Miaofen Du, Donghong Yan, Summer Park, Janice Kim, Min Xu, Benjamin D Sellers, Hans E Purkey, Nicholas Skelton, Michael F T Koehler, Jian Payandeh, Vishal Verma, Yiming Xu, Christopher M Koth, Mireille Nishiyama
There is a critical need for new antibacterial strategies to counter the growing problem of antibiotic resistance. In Gram-negative bacteria, the outer membrane (OM) provides a protective barrier against antibiotics and other environmental insults. The outer leaflet of the outer membrane is primarily composed of lipopolysaccharide (LPS). Outer membrane biogenesis presents many potentially compelling drug targets, as this pathway is absent in higher eukaryotes. Most proteins involved in LPS biosynthesis and transport are essential; however, few compounds have been identified that inhibit these proteins...
August 13, 2018: Antimicrobial Agents and Chemotherapy
Jane C Davies, Isaac Martin
Cystic fibrosis is characterized by bacterial lung infection, a majority of adults being chronically infected with Pseudomonas aeruginosa. Treatment is a major challenge, with frequent courses of antibiotics contributing to antimicrobial resistance. New approaches are clearly required. Over the last few years, a major shift in our approach to treating CF has occurred with the availability of the first drugs targeting the CFTR protein and leading to improvements in lung function, weight gain and frequency of exacerbations...
August 12, 2018: Expert Opinion on Pharmacotherapy
Zhan Gao, Baozhen Qu, Lan Yao, Zengyu Ma, Pengfei Cui, Shicui Zhang
Midkine (MK) and pleiotrophin (PTN) are the only two members of heparin-binding growth factor family. MK/PTN homologues found from Drosophila to humans are shown to have antibacterial activities and their antibacterial domains are conserved during evolution. However, little is known about MK/PTN homologue in the basal chordate amphioxus, and overall, information regarding MK/PTN homologues is rather limited in invertebrates. In this study, we identified a single MK/PTN homologue in Branchiostoma japonicum, termed BjMiple, which has a novel domain structure of PTN-PTNr1-PTNr2, and represents the ancestral form of vertebrate MK/PTN family proteins...
August 7, 2018: Developmental and Comparative Immunology
David Welch, Manuela Buonanno, Igor Shuryak, Gerhard Randers-Pehrson, Henry M Spotnitz, David J Brenner
Drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) are a target for new antimicrobial technologies. Far-UVC technology is an emerging disinfection method that directly kills microorganisms using light. In contrast with conventional UV sterilization, far-UVC light has antimicrobial capabilities without apparent harm to mammalian cells. This study examines the application of 224 nm far-UVC light delivered from a laser using an optical diffuser towards the goal of protecting against bacterial invasion around skin penetrating devices...
2018: PloS One
Jessica Nina Büttner, Marianne Schneider, Jaqueline Csokai, Elisabeth Müller, Johanna Corinna Eule
OBJECTIVES: To describe the bacterial and fungal microbiota of the conjunctiva and factors influencing these microbiota of healthy cats. To evaluate the antimicrobial resistance profile and discuss the use of appropriate antimicrobial drugs. ANIMALS STUDIED: One hundred and twenty healthy cats PROCEDURES: Conjunctival samples with dry or premoistened swabs were obtained from both eyes and cultured for aerobic and anaerobic bacteria and fungi. In vitro bacterial, susceptibility testing was performed...
August 10, 2018: Veterinary Ophthalmology
Xihong Zhao, Zhixue Yu, Zhenbo Xu
Staphylococcus aureus is a foodborne pathogen that causes food contamination and food poisoning, which poses great harm to health, agriculture and other hosts. Clustered regularly interspaced short palindromic repeats (CRISPR) are a recently discovered bacterial immune system that resists foreign genes such as phage DNA. This system inhibits the transfer of specific movable genetic elements that match the CRISPR spacer sequences, thereby preventing the spread of drug-resistant genes between pathogens. In this study, 57 CRISPR loci were screened from 38 strains of S...
2018: Frontiers in Microbiology
Muhsin Jamal, Saadia Andleeb, Fazal Jalil, Muhammad Imran, Muhammad Asif Nawaz, Tahir Hussain, Muhammad Ali, Sadeeq Ur Rahman, Chythanya Rajanna Das
Biofilm is involved in a variety of infections, playing a critical role in the chronicity of infections. Enterobacter cloacae is a biofilm-forming and multi-drug-resistant (MDR) nosocomial pathogen leading to significant morbidity and mortality. This study aimed at isolation of a bacteriophage against MDR clinical strain of E. cloacae and its efficacy against bacterial planktonic cells and biofilm. A bacteriophage MJ2 was successfully isolated from wastewater and was characterized. The phage exhibited a wide range of thermal and pH stability and demonstrated considerable adsorption to host bacteria in the presence of CaCl2 or MgCl2 ...
August 8, 2018: Folia Microbiologica
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