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File: /var/www/html/application/controllers/Detail.php
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Daptomycin is a last-line antibiotic commonly used to treat vancomycin-resistant Enterococci, but resistance evolves rapidly and further restricts already limited treatment options. While genetic determinants associated with clinical daptomycin resistance (DAP) have been described, information on factors affecting the speed of DAP acquisition is limited. The multiple peptide resistance factor (MprF), a phosphatidylglycerol-modifying enzyme involved in cationic antimicrobial resistance, is linked to DAP in pathogens such as methicillin-resistant Staphylococcus aureus. Since Enterococcus faecalis encodes two paralogs of mprF and clinical DAP mutations do not map to mprF, we hypothesized that functional redundancy between the paralogs prevents mprF-mediated resistance and masks other evolutionary pathways to DAP. Here, we performed in vitro evolution to DAP in mprF mutant background. We discovered that the absence of mprF results in slowed DAP evolution and is associated with inactivating mutations in ftsH, resulting in the depletion of the chaperone repressor HrcA. We also report that ftsH is essential in the parental, but not in the ΔmprF, strain where FtsH depletion results in growth impairment in the parental strain, a phenotype associated with reduced extracellular acidification and reduced ability for metabolic reduction. This presents FtsH and HrcA as enticing targets for developing anti-resistance strategies.
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http://dx.doi.org/10.1111/mmi.15253 | DOI Listing |
J Antimicrob Chemother
December 2024
Division of Infection Disease, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) are resistant to nearly all β-lactam antibiotics under standard testing conditions. However, a novel phenotype exists wherein certain MRSA strains exhibit β-lactam susceptibility in the presence of bicarbonate (termed 'NaHCO3-responsive'), an abundant ion in mammalian tissues and blood. This suggests that specific MRSA infections may be treatable by β-lactams.
View Article and Find Full Text PDFCommun Dis Intell (2018)
December 2024
School of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, Western Australia, Australia.
From 1 January to 31 December 2023, fifty-seven institutions across Australia participated in the Australian Surveillance Outcome Program (ASSOP). The aim of ASSOP 2023 was to determine the proportion of bacteraemia (SAB) isolates in Australia that were antimicrobial resistant, with particular emphasis on methicillin resistance, and to characterise the methicillin-resistant (MRSA) molecular epidemiology. A total of 3,422 SAB episodes were reported, of which 77.
View Article and Find Full Text PDFMicrobiologyopen
December 2024
Department of Life Sciences (DLS), Aberystwyth University, Aberystwyth, UK.
Antimicrobial resistance remains a global issue, hindering the control of bacterial infections. This study examined the antimicrobial properties of 2,3-N,N-diphenyl quinoxaline derivatives against Gram-positive, Gram-negative, and Mycobacterium species. Two quinoxaline derivatives (compounds 25 and 31) exhibited significant activity against most strains of Staphylococcus aureus, Enterococcus faecium, and Enterococcus faecalis tested, with MIC values ranging from 0.
View Article and Find Full Text PDFJ Infect Chemother
December 2024
Department of Infectious Diseases, Okayama University Hospital, Okayama, Japan; Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Introduction: Corynebacterium species potentially develop high-level daptomycin resistance (HLDR) shortly after daptomycin (DAP) administration. We aimed to investigate the clinical and microbiological characteristics of HLDR Corynebacterium infections.
Methods: We first presented a clinical case accompanied by the results of a comprehensive genetic analysis of the isolate, and then performed a systematic scoping review.
J Microbiol Immunol Infect
November 2024
Division of Pediatric Infectious Diseases, Chang Gung Memorial Hospital, 333, Taoyuan, Taiwan; Molecular Infectious Diseases Research Center, Chang Gung Memorial Hospital, 333, Taoyuan, Taiwan; Chang Gung University School of Medicine, 333 Taoyuan, Taiwan. Electronic address:
Background: Recurrent or persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia presents significant clinical challenges. Comprehensive genomic-scale studies on the genetic changes in MRSA that correspond to refractory bacteremia are lacking.
Method: From 2011 to 2019, MRSA blood isolates were collected from patients with persistent or recurrent bacteremia at a teaching hospital in southern Taiwan.
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