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Mechanisms of Antibiotic Resistance in Acinetobacter spp. — Genetics of Resistance
Published in E. Bergogne-Bénézin, M.L. Joly-Guillou, K.J. Towner, Acinetobacter, 2020
Aminoglycoside resistance in Gram-negative bacteria results most commonly from the action of plasmid- or transposon-encoded aminoglycoside-modifying enzymes which render aminoglycosides inactive. Three different types of modifying enzymes have been described: acetyltransferases (AAC), adenyl- or nucleotidyltransferases (AAD or ANT), and phosphotransferases (APH). Enzymes within each group are classified according to the aminoglycoside site of modifica-tion. Thus, there are four classes of acetyltransferases, AAC(l), AAC(3), AAC(6’) and AAC(2’), five of adenyltransferases, ANT(2"), ANT(3"), ANT(4’), ANT(6) and ANT(9), and five of phosphotransferases, APH(2"), APH(3’), APH(3"), APH(6) and APH(4). Several of the enzymes can be subdivided further according to their aminoglycoside resistance profile (designated by a Roman numeral suffix) and unique protein nature (designated by a lower-case alphabetical suffix). Hence, AAC(6’)-Ia and AAC(6’)-Ib express identical aminoglycoside resistance profiles, but differ in their protein sequence (Shaw et al., 1993).
Pseudomonas aeruginosa
Published in Firza Alexander Gronthoud, Practical Clinical Microbiology and Infectious Diseases, 2020
Aminoglycoside-modifying enzymes (AME) Acetyltransferases (AAC), phosphotransferases (APH) and nucleotidyltransferases (ANT).Among aminoglycoside resistance, resistance to gentamicin develops first followed by tobramycin and later on amikacin.Tobramycin is more potent against P. aeruginosa than gentamicin.
RNA
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
As Fiers (1975) noticed, the most important conclusion that could be drawn from the 3′-terminal sequence was that it contained none of the termination codons for polypeptide synthesis: UAA, UAG, or UGA. It was the first indication that the 3′-end of a polynucleotide was not sufficient for the polypeptide chain release by the ribosome and that the terminal non-translated region must serve another important function. Another interesting finding was that the last three nucleotides, namely CCA, were the same as found in all tRNAs. This terminal sequence had already been identified as the 3′-end of tobacco mosaic virus (TMV) RNA by Steinschneider and Fraenkel-Conrat (1966) and was later also found at the 3′-end of the Qβ RNA (Dahlberg 1968) and of brome grass mosaic virus RNA (Glitz and Eichler 1971). Although R17 RNA-pC and R17 RNA-pCpC lacking 1 or 2 cytidine residues, respectively, were unable to accept nucleoside monophosphates in the enzymic reaction catalyzed by tRNA 3′-terminal nucleotidyltransferase, it was found that they were able to form complexes with the enzyme (Igarashi and McCalla 1971).
Plant-Derived Natural Non-Nucleoside Analog Inhibitors (NNAIs) against RNA-Dependent RNA Polymerase Complex (nsp7/nsp8/nsp12) of SARS-CoV-2
Published in Journal of Dietary Supplements, 2023
Sreus A. G. Naidu, Ghulam Mustafa, Roger A. Clemens, A. Satyanarayan Naidu
The RdRp complex of SARS-CoV-2 consists of a nsp12 core catalytic unit, a nsp7-nsp8 (nsp8-1) heterodimer, and an additional nsp8 subunit (nsp8-2) (23, 38). The RdRp structure has a ‘polymerase’ domain (residues Ser367 to Phe920) that resembles a cupped ‘right hand’ and a unique nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain (residues Asp60 to Arg249), where both interact through an ‘interface’ domain (residues Ala250 to Arg365) (23, 39). This domain also consists of the ‘fingers’ subdomain (residues Leu366-Ala581 and Lys621-Gly679), the ‘palm’ subdomain (residues Thr582-Pro620 and residues Thr680-Gln815), and the ‘thumb’ subdomain (residues His816-Glu920) (40). The ‘finger’ subdomain stabilizes the template RNA and facilitates specific interactions with major residues in the active enzymatic site (41). The ‘thumb’ subdomain harbors residues that pack against the template RNA and stabilizes the nucleoside triphosphates (NTPs) on the template (42). This subdomain translocates the template RNA after polymerization and accommodates any conformational rearrangements. There is an N-terminal β-hairpin (residues Asp29 to Lys50) between the ‘palm’ subdomain and the ‘NiRAN’ domain that help stabilize the RdRp structure (Figure 1A) (23).
Hematopoietic stem cell transplantation in systemic autoinflammatory diseases - the first one hundred transplanted patients
Published in Expert Review of Clinical Immunology, 2022
Sara Signa, Gianluca Dell’Orso, Marco Gattorno, Maura Faraci
Patients with SIFD (Sideroblastic anemia with B-cell Immunodeficiency, periodic fever, and Developmental delay) present loss of function (LOF) homozygous or compound heterozygous mutations in the TRNT1 gene, coding for tRNA nucleotidyltransferase cytidine-cytidine- adenosine-adding 1, implicated in tRNAs maturation. The clinical picture is characterized by an early onset systemic inflammation with musculoskeletal and mucocutaneous alterations, associated with developmental delay [26,27]. Activation of UPR causes an abnormal B cell maturation leading to immunoglobulin (Ig) deficiency [28]. Anti-tumor necrosis factor (TNF) treatments are more effective than IL-1 inhibitors in these patients [7]. HSCT can correct the immunological and hematological defect, with resolution of inflammation and independence from transfusions and IVIG (intravenous immunoglobulin) replacement [26,27,29]. However, the neurologic manifestations possibly associated with this condition do not benefit from HSCT [29]: in fact, development of pigmentary retinitis in one patient was reported some years after HSCT [26]. At present, only four transplanted patients are described and one of them died soon after transplant due to a pulmonary hemorrhage [27,29] (Table 2).
Analysis of 1135 gut metagenomes identifies sex-specific resistome profiles
Published in Gut Microbes, 2019
Trishla Sinha, Arnau Vich Vila, Sanzhima Garmaeva, Soesma A. Jankipersadsing, Floris Imhann, Valerie Collij, Marc Jan Bonder, Xiaofang Jiang, Thomas Gurry, Eric J. Alm, Mauro D’Amato, Rinse K. Weersma, Sicco Scherjon, Cisca Wijmenga, Jingyuan Fu, Alexander Kurilshikov, Alexandra Zhernakova
When taking into account the medications used by both sexes, we observed that male LLD participants took more drugs for heart disease, while women were more exposed to opiates, laxatives and antibiotics. The last category is of particular interest, as antibiotics have been shown to have profound effects on microbiota composition,27-29,36 and to represent a risk factor for GI diseases.28 To better characterize the sex-related differences, we therefore performed (age-adjusted) gut metagenomic analyses of resistome profiles, focusing on AR genes and classes from CARD. What we found is that men and women differed significantly in the resistome richness of their gut microbiome. Females showed a greater mean prevalence of AR genes (65.4 versus 60.7, p = 0.004), and this was also reflected at gene family level (24.0 versus 23.0, p = 0.04). The most notable difference was observed for the lincosamide nucleotidyltransferase (LNU) gene family, which was present in 85.98% of women compared to 79.07% of men (Table 1). In the Netherlands, lincosamide antibiotics are indicated for bacterial vaginosis and Pelvic Inflammatory Disease37 (among other conditions), and the prevalence of women consuming macrolide, lincosamide and streptogramin (MLS) antibiotics has been consistently higher than that in men during the past 5 years.38 In 2016, MLS antibiotics were consumed by 3.53% of women versus 2.58% of men. The resistome profiles detected in our cohort thus appear to follow national trends in sex-related differences in antibiotic use.