The rapid increased multidrug resistance in has led to a renewed interest in polymyxin antibiotics, such as colistin, as antibiotics of last resort, not least in low/middle income countries. We conducted a genomic survey of clinical polymyxin-resistant to investigate the genetic alterations in isolates harboring . Whole-genome sequencing was performed using an Illumina NextSeq 500 paired-end reads. Mutations and insertion sequence detection were analyzed to seven isolates recovered from clinical specimens of patients hospitalized in Brazil, focusing on key genes associated with polymyxin resistance. Furthermore, the levels of mRNA expression of genes associated with resistance to polymyxin B and other antimicrobials were evaluated by quantitative real-time PCR. Eighty-five percent of the isolates were assigned to clonal complex 258, with a minimum inhibitory concentration range of 4 to >256 mg/L for polymyxin B. It was possible to observe the presence of one important insertion element, IS, in a strain recovered from the blood that have . Deleterious mutations reported in PmrB (R256G), YciM (N212T), and AcrB (T598A) were common, and mobile colistin resistance () genes were absent in all the isolates. RT-qPCR analysis revealed an overexpression of the (1.160-fold), (2.258-fold), and (1.530-fold) genes in the polymyxin B-resistant isolates compared with the expression of the polymyxin B-susceptible isolate. Overall, these results demonstrate the diversity of genetic variations in polymyxin-resistant populations derived from the different clonal strains, but the same sequence types, and suggest that there are still unknown mechanisms of polymyxin resistance in .
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http://dx.doi.org/10.1089/mdr.2020.0531 | DOI Listing |
Unlabelled: is a high-priority organism for the development of new antibacterial treatments. We found that the antimalarial medication mefloquine (MFQ) permeabilized the bacterial cell membrane of , decreased membrane fluidity, and caused physical injury to the membrane. MFQ also maintained activity across different pH conditions (PH range 5-8).
View Article and Find Full Text PDFProtein Sci
February 2025
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
Polymyxins are last-resort antimicrobial peptides administered clinically against multi-drug resistant bacteria, specifically in the case of Gram-negative species. However, an increasing number of these pathogens employ a defense strategy that involves a relay of enzymes encoded by the pmrE (ugd) loci and the arnBCDTEF operon. The pathway modifies the lipid-A component of the outer membrane (OM) lipopolysaccharide (LPS) by adding a 4-amino-4-deoxy-l-arabinose (L-Ara4N) headgroup, which renders polymyxins ineffective.
View Article and Find Full Text PDFJ Glob Antimicrob Resist
January 2025
Grupo Fleury, São Paulo, Brazil.
Objectives: This study aimed to describe the epidemiology and antimicrobial susceptibility patterns of gram-negative pathogens in Brazil from 2018 to 2020, addressing the gap in national data on healthcare-associated infections, using information from a private laboratory network.
Methods: A cross-sectional study was conducted using a database from Fleury hospital network, a private laboratory in Brazil. The analysis included blood, urine, and lower respiratory tract samples collected from January 2018 to June 2020.
J Infect Dev Ctries
December 2024
Faculdade de Farmácia, Universidade Federal de Minas Gerais, Brazil.
Introduction: Antimicrobial resistance (AMR) is a major public health challenge globally. This study aimed to analyze the antibacterial consumption (ATBc), and the incidence of multidrug-resistant organisms (MDRO), focusing on pathogens Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE group), in a Brazilian tertiary care hospital.
View Article and Find Full Text PDFPharmaceutics
January 2025
Center for Pharmacy, University of Bergen, 5020 Bergen, Norway.
Polymyxin E (PME), a polymyxin antibiotic, serves as a final resort against antibiotic resistance. Nephrotoxicity is the primary concern when employing PME. To alleviate this issue, researchers have explored strategies including dosing adjustments and innovative formulations.
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