Genomic analysis of multidrug-resistant CTX-M-15-positive Klebsiella pneumoniae belonging to the highly successful ST15 clone isolated from a dog with chronic otitis
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
Authors: Sellera, Fabio P.; Lopes, Ralf; Monte, Daniel F. M.; Cardoso, Brenda; Esposito, Fernanda; dos Anjos, Carolina; da Silva, Luciano C. B. A.; Lincopan, Nilton
Abstract
Background: Extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae have been increasingly reported worldwide as a frequent cause of human and animal infections. K. pneumoniae belonging to the K24 capsular serotype and sequence type (ST) ST15 has been considered a global successful clone responsible for the spread of the bla(CTX-M-15) gene. Objective: To report the draft genome sequence of a multidrug-resistant CTX-M-15-positive K. pneumoniae K24-ST15 strain (L3KP1), which was isolated from a dog with chronic otitis. Methods: Genomic DNA was extracted and sequenced using Illumina NextSeq platform. De novo assembly was performed by SPAdes and in silico prediction accomplished by curated bioinformatics tools. Results: The genome size was calculated at 5 642 348 bp, with a GC content of 57.11%, and comprising 5601 total genes, 52 tRNAs, 8 rRNAs, 9 ncRNAs and 105 pseudogenes. The K. pneumoniae L3KP1 strain belonged to ST15 and carried the yersiniabactin biosynthetic gene cluster [ybt 10 (YbST28) in the integrative conjugative element ICEKp4], and the KL24 locus encoding capsular serotype K24. Besides the bla(CTX-M-15) ESBL gene, other clinically important resistance genes to beta-lactams, aminoglycosides, fosfomycin, macrolides, phenicol, quinolones, sulfonamides, tetracyclines and trimethoprim were detected. Additionally, heavy metals and disinfectant resistance genes were also identified. Conclusion: This draft genome might be useful for comparative genomic analyses of the international clone of K. pneumoniae K24-ST15-CTX-M-15. In addition, information presented in this study also shed light on the urgent need to monitor ESBL-producing K. pneumoniae in veterinary hospitals. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.
Optimization of 4-Substituted Benzenesulfonamide Scaffold To ReverseAcinetobacter baumanniiSerum-Adaptive Efflux Associated Antibiotic Tolerance
CHEMMEDCHEM
Authors: Chojnacki, Michaelle; Cao, Xufeng; Young, Mikaeel; Fritz, Rebecca N.; Dunman, Paul M.; Flaherty, Daniel P.
Abstract
Acinetobacter baumanniiis a nosocomial pathogen of urgent concern for public health due to rising rates of multidrug and pandrug resistance. In the context of environmental cues such as growth in human serum,A. baumanniiis known to display adaptive efflux, in which a multitude of efflux-associated genes are upregulated, resulting in efflux-mediated drug tolerance in strains that are otherwise susceptible to antibiotic therapy. Previously, we identified a sulfonamide-containing scaffold molecule (ABEPI1) that reversed serum-associated antibiotic tolerance inA. baumannii. Herein, we present structure-activity relationship studies on 29 newly synthesized analogues. These molecules were characterized for their ability to potentiate multiple antibiotics in serum, reduce serum-associated ethidium bromide efflux and depolarize bacterial cell membranes. In addition, they were assessed for toxicity to mammalian cells. Collectively, these molecules may represent promising potential adjuvants for use in combination with new and existing antibiotics to treatA. baumanniibacterial infections.