Safer In Vitro Drug Screening Models for Melioidosis Therapy Development.

Safer In Vitro Drug Screening Models for Melioidosis Therapy Development. Am J Trop Med Hyg. 2020 Sep 21;: Authors: Amiss AS, Webb JR, Mayo M, Currie BJ, Craik DJ, Henriques ST, Lawrence N Abstract Melioidosis is a neglected tropical disease caused by the Gram-negative soil bacterium Burkholderia pseudomallei. Current antibiotic regimens used to treat melioidosis are prolonged and expensive, and often ineffective because of intrinsic and acquired antimicrobial resistance. Efforts to develop new treatments for melioidosis are limited by the risks associated with handling pathogenic B. pseudomallei, which restricts research to facilities with biosafety level three containment. Closely related nonpathogenic Burkholderia can be investigated under less stringent biosafety level two containment, and we hypothesized that they could be used as model organisms for developing therapies that would also be effective against B. pseudomallei. We used microbroth dilution assays to compare drug susceptibility profiles of three B. pseudomallei strains and five nonpathogenic Burkholderia strains. Burkholderia humptydooensis, Burkholderia thailandensis, and Burkholderia territorii had similar susceptibility profiles to pathogenic B. pseudomallei that support their potential as safer in vitro models for developing new melioidosis therapies. PMID: 32975176 [PubMed - as supplied by publisher]
Source: The American Journal of Tropical Medicine and Hygiene - Category: Tropical Medicine Authors: Tags: Am J Trop Med Hyg Source Type: research

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Publication date: June 2020Source: Journal of Global Antimicrobial Resistance, Volume 21Author(s): Xuming Wang, Xiao Zheng, Meihui Huang, Lingli Liu
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
ConclusionsThe reduced growth speed and increased drug resistance of B. pseudomallei SCV strain may be related to those variations in genome, which provided some clues to their associations between the morphotypic and phenotypic characteristics of colony variants, and the potential associations of its colony morphotypes with metabolism, antibiotic resistance and virulence.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
ConclusionThe results of this study suggest that currently recommended antibiotics for melioidosis treatment can be empirically used, but continuously monitoring antimicrobial susceptibility should be a concern.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
This study was carried out in accordance with the recommendations of “Gene Recombinant Experiment Applications” and “Biological Materials Applications,” Biosafety Committee, National Yang-Ming University. The protocol was approved by the Biosafety Committee. All subjects gave written informed consent in accordance with the Declaration of Helsinki. Results FQ Susceptibility of Clinical Isolates To investigate the underlying FQ resistance mechanisms of S. maltophilia, 125 clinical isolates were selected from different sources (sputum, 75; aspirate of respiratory tract, 19; blood, 9; urine, 6; pus/w...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
This study was supported by the Israel Institute for Biological Research, Ness Ziona, Israel. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We thank Dr. Vered Caspi (Ben-Gurion University) for assisting with the bioinformatics and statistical analyses of the Agilent DNA microarray results. Supplementary Material The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmicb.2019.00754/full#s...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
In conclusion, this study will help to enhance our understanding of molecular characteristics and antibiotic resistance of B pseudomallei.
Source: Medicine - Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research
ConclusionThe results of the study suggests that currently recommended antibiotics for meliodiosis treatment can be used emperically but monitoring continuously antimicrobial susceptibility should be concerned.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
AbstractPurpose of ReviewAroused by the capacity of bacteria to develop antimicrobial resistance which allows them to persist in patient under antibiotic treatment, and their adaptation to host defenses by modifying their virulence, we review the relationship between antibiotic resistance and virulence inBurkholderia pseudomallei.Recent FindingFew studies focused on both antibiotic resistance and virulence. The relationship between these two mechanisms is very complex. Main resistance mechanisms such as efflux, biofilm, morphological changes or persistence are linked to virulence but results are still controversial. Recent...
Source: Current Tropical Medicine Reports - Category: Tropical Medicine Source Type: research
In this study, we assess using broth microdilution the MIC of meropenem, ceftazidime, TMP-SMX and doxycycline for a library of 234 well characterised clinical isolates of B. pseudomallei from northern Queensland, Australia. The resultant histograms and aggregate data represent the first MIC profile of a large library of B. pseudomallei that has been successfully produced using microbroth dilution. The MIC profiles can be used to contribute towards a determination of an ECOFF for this species for these agents, which will aid in the setting and refining of clinical breakpoints for the most important antimicrobials used to treat melioidosis.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
This study provides the first evidence that mutations in penA may alter susceptibility to carbapenems in B. pseudomallei Another mutation of interest was a point mutation affecting the dihydrofolate reductase gene folA, which likely explains the trimethoprim resistance of this strain. Bp1651 was susceptible to aminoglycosides likely due to a frame shift in the amrB gene, the transporter subunit of the AmrAB-OprA efflux pump. These findings expand the role of penA to include resistance to carbapenems and may assist in development of molecular diagnostics that predict antimicrobial resistance and provide guidance for treatme...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
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