scholarly journals Acinetobacter baumannii Antibiotic Resistance Mechanisms

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 373
Author(s):  
Ioannis Kyriakidis ◽  
Eleni Vasileiou ◽  
Zoi Dorothea Pana ◽  
Athanasios Tragiannidis

Acinetobacter baumannii is a Gram-negative ESKAPE microorganism that poses a threat to public health by causing severe and invasive (mostly nosocomial) infections linked with high mortality rates. During the last years, this pathogen displayed multidrug resistance (MDR), mainly due to extensive antibiotic abuse and poor stewardship. MDR isolates are associated with medical history of long hospitalization stays, presence of catheters, and mechanical ventilation, while immunocompromised and severely ill hosts predispose to invasive infections. Next-generation sequencing techniques have revolutionized diagnosis of severe A. baumannii infections, contributing to timely diagnosis and personalized therapeutic regimens according to the identification of the respective resistance genes. The aim of this review is to describe in detail all current knowledge on the genetic background of A. baumannii resistance mechanisms in humans as regards beta-lactams (penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors), aminoglycosides, tetracyclines, fluoroquinolones, macrolides, lincosamides, streptogramin antibiotics, polymyxins, and others (amphenicols, oxazolidinones, rifamycins, fosfomycin, diaminopyrimidines, sulfonamides, glycopeptide, and lipopeptide antibiotics). Mechanisms of antimicrobial resistance refer mainly to regulation of antibiotic transportation through bacterial membranes, alteration of the antibiotic target site, and enzymatic modifications resulting in antibiotic neutralization. Virulence factors that may affect antibiotic susceptibility profiles and confer drug resistance are also being discussed. Reports from cases of A. baumannii coinfection with SARS-CoV-2 during the COVID-19 pandemic in terms of resistance profiles and MDR genes have been investigated.

2017 ◽  
Vol 4 ◽  
pp. 1-53 ◽  
Author(s):  
Paul Murphey ◽  
K.E. Townsend ◽  
Anthony Friscia ◽  
James Westgate ◽  
Emmett Evanoff ◽  
...  

The Bridger Formation is restricted to the Green River Basin in southwest Wyoming, and the Uinta and Duchesne River Formations are located in the Uinta Basin in Utah. These three rock units and their diverse fossil assemblages are of great scientific importance and historic interest to vertebrate paleontologists. Notably, they are also the stratotypes from oldest to youngest for the three middle Eocene North American Land Mammal Ages—the Bridgerian, Uintan, and Duchesnean. The fossils and sediments of these formations provide a critically important record of biotic, environmental, and climatic history spanning approximately 10 million years (49 to 39 Ma). This article provides a detailed field excursion through portions of the Green River and Uinta Basins that focuses on locations of geologic, paleontologic, and historical interest. In support of the field excursion, we also provide a review of current knowledge of these formations with emphasis on lithostratigraphy, biochronology, depositional, and paleoenvironmental history, and the history of scientific exploration.


Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 682
Author(s):  
Matthias Christen ◽  
Nils Janzen ◽  
Anne Fraser ◽  
Adrian C. Sewell ◽  
Vidhya Jagannathan ◽  
...  

A 7-month-old, spayed female, domestic longhair cat with L-2-hydroxyglutaric aciduria (L-2-HGA) was investigated. The aim of this study was to investigate the clinical signs, metabolic changes and underlying genetic defect. The owner of the cat reported a 4-month history of multiple paroxysmal seizure-like episodes, characterized by running around the house, often in circles, with abnormal behavior, bumping into obstacles, salivating and often urinating. The episodes were followed by a period of disorientation and inappetence. Neurological examination revealed an absent bilateral menace response. Routine blood work revealed mild microcytic anemia but biochemistry, ammonia, lactate and pre- and post-prandial bile acids were unremarkable. MRI of the brain identified multifocal, bilaterally symmetrical and T2-weighted hyperintensities within the prosencephalon, mesencephalon and metencephalon, primarily affecting the grey matter. Urinary organic acids identified highly increased levels of L-2-hydroxyglutaric acid. The cat was treated with the anticonvulsants levetiracetam and phenobarbitone and has been seizure-free for 16 months. We sequenced the genome of the affected cat and compared the data to 48 control genomes. L2HGDH, coding for L-2-hydroxyglutarate dehydrogenase, was investigated as the top functional candidate gene. This search revealed a single private protein-changing variant in the affected cat. The identified homozygous variant, XM_023255678.1:c.1301A>G, is predicted to result in an amino acid change in the L2HGDH protein, XP_023111446.1:p.His434Arg. The available clinical and biochemical data together with current knowledge about L2HGDH variants and their functional impact in humans and dogs allow us to classify the p.His434Arg variant as a causative variant for the observed neurological signs in this cat.


Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 875
Author(s):  
Tomasz Bogiel ◽  
Mateusz Rzepka ◽  
Eugenia Gospodarek-Komkowska

Non-fermenting Gram-negative rods are one of the most commonly isolated bacteria from human infections. These microorganisms are typically opportunistic pathogens that pose a serious threat to public health due to possibility of transmission in the human population. Resistance to beta-lactams, due to carbapenemases synthesis, is one of the most important antimicrobial resistance mechanisms amongst them. The aim of this study was to evaluate the usefulness of the Carbapenem Inactivation Method (CIM), and its modifications, for the detection of carbapenemase activity amongst non-fermenting Gram-negative rods. This research involved 81 strains of Gram-negative rods. Of the tested strains, 55 (67.9%) synthesized carbapenemases. For non-fermenting rods, 100% sensitivity and specificity was obtained in the version of the CIM test using imipenem discs and E. coli ATCC 25922 strain. The CIM test allows for differentiation of carbapenems resistance mechanisms resulting from carbapenemase synthesis from other resistance types. It is a reliable diagnostic method for the detection of carbapenemase activity amongst non-fermenting Gram-negative rods. Application of imipenem discs and P. aeruginosa ATCC 27853 reference strain increases CIM results sensitivity, while imipenem discs and E. coli ATCC 25922 strain use maintains full precision of the test for non-fermenting rods.


2009 ◽  
Vol 4 (3) ◽  
pp. 258-273 ◽  
Author(s):  
Giovanna Pirri ◽  
Andrea Giuliani ◽  
Silvia Nicoletto ◽  
Lorena Pizzuto ◽  
Andrea Rinaldi

AbstractLipopeptide antibiotics represent an old class of antibiotics that were discovered over 50 years ago, which includes the old polymyxins but also new entries, such as the recently approved daptomycin. They generally consist of a hydrophilic cyclic peptide portion attached to a fatty acid chain which facilitates insertion into the lipid bilayer of bacterial membranes. This review presents an overview of this class of antibiotics, focusing on their therapeutic applications and putting particular emphasis on chemical modifications introduced to improve their activity.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Victoria Hale ◽  
Maren Weischer ◽  
Jong Y. Park

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer.CHEK2plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, ofCHEK2on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussedCHEK2∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18) for unselected cases and 3.39 (1.78–6.47) for familial cases, indicating thatCHEK2∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Ahmed Z Obeidat ◽  
Heidi Sucharew ◽  
Charles J Moomaw ◽  
Dawn O Kleindorfer ◽  
Brett M Kissela ◽  
...  

Background: Current knowledge on ischemic stroke in sarcoid patients stems from sporadic case reports. The mechanism is thought to be related to granulomatous involvement of brain vasculature. However, clinical, demographic, and radiographic features of sarcoid patients with ischemic stroke are lacking. If sarcoid patients are at higher risk for ischemic stroke event, we hypothesized that the risk factors for ischemic stroke and stroke subtype distribution would differ between sarcoid and non-sarcoid ischemic stroke patients. Methods: Cases of ischemic stroke were identified for the years 2005 and 2010 from the population-based Greater Cincinnati/Northern Kentucky Stroke Study (population 1.3 million). Ischemic stroke cases were physician study confirmed and patients with a history of sarcoid were identified through medical chart review. Clinical variables were compared between stroke patients with history of sarcoid and those with no prior sarcoid history. Results: A total of 4258 cases of ischemic stroke were identified; of them, only 18 had prior diagnosis of sarcoid (0.04%). Brain MRI showed diffusion restriction in 14 out of 15 (93%) MRIs performed in sarcoid patients. The table presents risk factor and subtype data on sarcoid patients compared with non-sarcoid patients. Conclusions: We identified only a few cases of prior sarcoid history in our two-year ascertainment of ischemic stroke patients in our population. In comparison with stroke patients with no prior history of sarcoid, the sarcoid patients tended to be of younger age at presentation, female, have a history of diabetes and hyperlipidemia, and more likely of African descent, perhaps related to the diagnosis of sarcoid itself. We were unable to detect differences in stroke subtype distributions between sarcoid and non-sarcoid ischemic stroke patients.


2017 ◽  
Vol 8 (1-IT) ◽  
Author(s):  
Mario Tanga ◽  
Giacomo Gelati ◽  
Marco Casazza

6Contemporary science and culture show more and more extended and meaningful signs about the increasing explaining power of evolutionary paradigm. This power overcomes the field of the history of living species. We consider “On the Origin of Species” of 1859 by Charles Darwin as the establishment of this paradigm, but this original and fruitful idea has received the several and different contributions from near and (seemingly) far scientific fields. This process happened according distinguishable waves and leaded the evolutionary theory very far from its starting point, making it something wider and different. The current knowledge of this theory involves many kinds of scholars: biologists, zoologists, botanists, development biologists, genetics/genomics scholars and also scholars of many other disciplines, as statistics, mathematics, ecology, environmental sciences, physics, chemistry, linguistics, sociology, neuro-sciences, epidemiology, informatics, immunology. During the end of XX Century, the study of complexity, of self-organization and of emerging properties has been a decisive factor to extend evolution until beyond the boundaries of Biology. These phenomena, or properties, or features, that are shown by “living” and “not-living” systems (so called basing ourselves on traditional definitions), have deeply modified even the “properly” biologic evolution itself and besides this has demonstrated that, mutatis mutandis, evolutionary processes or phenomena happen also out of biologic dominion, referring “biologic” to “wet-ware world”. This is to say the class of evolutionary phenomena is more widely and more inclusively extended than our opinion. We can mean this as a revolution (according to Kuhn’s definition) that imposes us to restructure the definition of evolution itself and even to redraw the boundaries and the map of Biology itself. Aiming to establish a name of this field of study we propose “PanEvolutionary Theory” (PanEvo Theory). No doubt Prigogine offered an important contribution to this area. The thinking and the work of Enzo Tiezzi can be placed seen in the same perspective. Disregarding direct connections and contacts with the Nobel Prize Prigogine, however the studies of Enzo Tiezzi are neither a fully unexpected work nor a theory lacking of important potentialities: it is not a strange or eccentric academic exercise. Except the close contact and the dense exchanges with Prigogine, we collocate Enzo Tiezzi in the same context of Gregory Chaitin, of Rachel Carson, of John Harte and Robert H. Socolow, of James Paul Wesley, of Sertorio, of Oort and Peixoto, just to cite the most strictly related. Our Academy had the privilege and the honor of having Enzo Tiezzi in its ranks. We think that merits and developments of the thinking of this scholar have to produce important and lasting fruits in the future.


2017 ◽  
Vol 87 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Raquel Girardello ◽  
Marina Visconde ◽  
Rodrigo Cayô ◽  
Regina Célia Bressan Queiroz de Figueiredo ◽  
Marcelo Alves da Silva Mori ◽  
...  

2020 ◽  
Vol 105 (1) ◽  
pp. 55-66
Author(s):  
Wolfgang Hüttel

Abstract Echinocandins are a clinically important class of non-ribosomal antifungal lipopeptides produced by filamentous fungi. Due to their complex structure, which is characterized by numerous hydroxylated non-proteinogenic amino acids, echinocandin antifungal agents are manufactured semisynthetically. The development of optimized echinocandin structures is therefore closely connected to their biosynthesis. Enormous efforts in industrial research and development including fermentation, classical mutagenesis, isotope labeling, and chemical synthesis eventually led to the development of the active ingredients caspofungin, micafungin, and anidulafungin, which are now used as first-line treatments against invasive mycosis. In the last years, echinocandin biosynthetic gene clusters have been identified, which allowed for the elucidation but also engineering of echinocandin biosynthesis on the molecular level. After a short description of the history of echinocandin research, this review provides an overview of the current knowledge of echinocandin biosynthesis with a special focus of the diverse structural elements, their biosynthetic background, and structure−activity relationships. Key points • Complex and highly oxidized lipopeptides produced by fungi. • Crucial in the design of drugs: side chain, solubility, and hydrolytic stability. • Genetic methods for engineering biosynthesis have recently become available.


Author(s):  
Wojciech Sowa

Thracian belongs to the group of languages spoken over the entire period of Antiquity in the areas of south-eastern Europe (mostly the Balkans) and which, like other vernaculars spoken in this and neighbouring areas, had died out by the end of the Roman period leaving but scanty evidence. This chapter provides an introduction into the state of our current knowledge about the Thracian language and epigraphy and the perspectives of research of this language. Since our comprehension and understanding of grammatical system of Thracian is limited, the current knowledge of the language makes any translation of attested inscriptions impossible. It is however expected that the progress in studying development and history of the Greek script may provide us with new and relevant data for interpretation of Thracian.


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