Joshua Benjamin Parsons

Journal Article Sci Adv · February 14, 2025 Individuals with diabetes mellitus frequently develop severe skin and soft tissue infections (SSTIs) that are recalcitrant to antibiotic treatment. We examined how diabetes affects the emergence of antibiotic resistance in a Staphylococcus aureus SSTI. We ... Full text Link to item Cite

Palmitoleic acid sensitizes vancomycin-resistant Staphylococcus aureus to vancomycin by outpacing the expression of resistance genes.

Journal Article Microbiol Spectr · January 7, 2025 The rise in antibiotic resistance limits the availability of antibiotics to treat bacterial infections. Despite this, antibiotic development pipelines remain sparse which makes using adjuvants to reverse antibiotic resistance a promising therapeutic strate ... Full text Link to item Cite

Persistent Gram-negative Bloodstream Infection Increases the Risk of Recurrent Bloodstream Infection With the Same Species.

Journal Article Clin Infect Dis · June 14, 2024 The association between persistent gram-negative bloodstream infection (GN-BSI), or ongoing positive cultures, and recurrent GN-BSI has not been investigated. Among 992 adults, persistent GN-BSI was associated with increased recurrent GN-BSI with the same ... Full text Link to item Cite

Female Sex and Mortality in Patients with Staphylococcus aureus Bacteremia: A Systematic Review and Meta-analysis.

Journal Article JAMA Netw Open · February 5, 2024 IMPORTANCE: Staphylococcus aureus is the leading cause of death due to bacterial bloodstream infection. Female sex has been identified as a risk factor for mortality in S aureus bacteremia (SAB) in some studies, but not in others. OBJECTIVE: To determine w ... Full text Link to item Cite

In-patient evolution of a high-persister Escherichia coli strain with reduced in vivo antibiotic susceptibility.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · January 2024 Gram-negative bacterial bloodstream infections (GNB-BSI) are common and frequently lethal. Despite appropriate antibiotic treatment, relapse of GNB-BSI with the same bacterial strain is common and associated with poor clinical outcomes and high healthcare ... Full text Cite

Inflammasome-mediated glucose limitation induces antibiotic tolerance in Staphylococcus aureus.

Journal Article iScience · October 20, 2023 Staphylococcus aureus is a leading human pathogen that frequently causes relapsing infections. The failure of antibiotics to eradicate infection contributes to infection relapse. Host-pathogen interactions have a substantial impact on antibiotic susceptibi ... Full text Link to item Cite

Antibiotic-induced accumulation of lipid II synergizes with antimicrobial fatty acids to eradicate bacterial populations.

Journal Article Elife · March 6, 2023 Antibiotic tolerance and antibiotic resistance are the two major obstacles to the efficient and reliable treatment of bacterial infections. Identifying antibiotic adjuvants that sensitize resistant and tolerant bacteria to antibiotic killing may lead to th ... Full text Link to item Cite

Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia: Host, Pathogen, and Treatment.

Journal Article Antibiotics (Basel) · February 24, 2023 Methicillin-resistant Staphylococcus aureus (MRSA) is a devastating pathogen responsible for a variety of life-threatening infections. A distinctive characteristic of this pathogen is its ability to persist in the bloodstream for several days despite seemi ... Full text Link to item Cite

Clinical and Molecular Analyses of Recurrent Gram-Negative Bloodstream Infections.

Journal Article Clin Infect Dis · February 8, 2023 BACKGROUND: The causes and clinical characteristics of recurrent gram-negative bacterial bloodstream infections (GNB-BSI) are poorly understood. METHODS: We used a cohort of patients with GNB-BSI to identify clinical characteristics, microbiology, and risk ... Full text Link to item Cite

Association of Follow-up Blood Cultures With Mortality in Patients With Gram-Negative Bloodstream Infections: A Systematic Review and Meta-analysis.

Journal Article JAMA network open · September 2022 ImportanceObtaining follow-up blood cultures (FUBCs) in patients with Staphylococcus aureus bloodstream infection (BSI) is standard practice, although its utility in patients with gram-negative bacterial BSI (GN-BSI) is unclear.ObjectiveT ... Full text Cite

Hemophagocytic Lymphohistiocytosis Associated With Endocarditis: A Case Years in the Making.

Journal Article Circulation · March 22, 2022 Full text Link to item Cite

Vancomycin Heteroresistance and Clinical Outcomes in Bloodstream Infections Caused by Coagulase-Negative Staphylococci.

Journal Article Antimicrob Agents Chemother · October 20, 2020 Coagulase-negative staphylococci (CoNS) are a common etiology of serious and recurrent infections in immunocompromised patients. Although most isolates appear susceptible to vancomycin, a single strain might have a subpopulation of resistant bacteria. This ... Full text Link to item Cite

A thioesterase bypasses the requirement for exogenous fatty acids in the plsX deletion of Streptococcus pneumoniae.

Journal Article Molecular microbiology · April 2015 PlsX is an acyl-acyl carrier protein (ACP):phosphate transacylase that interconverts the two acyl donors in Gram-positive bacterial phospholipid synthesis. The deletion of plsX in Staphylococcus aureus results in a requirement for both exogenous fatty acid ... Full text Cite

FabH mutations confer resistance to FabF-directed antibiotics in Staphylococcus aureus.

Journal Article Antimicrob Agents Chemother · February 2015 Delineating the mechanisms for genetically acquired antibiotic resistance is a robust approach to target validation and anticipates the evolution of clinical drug resistance. This study defines a spectrum of mutations in fabH that render Staphylococcus aur ... Full text Link to item Cite

Identification of a two-component fatty acid kinase responsible for host fatty acid incorporation by Staphylococcus aureus.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · July 2014 Extracellular fatty acid incorporation into the phospholipids of Staphylococcus aureus occurs via fatty acid phosphorylation. We show that fatty acid kinase (Fak) is composed of two dissociable protein subunits encoded by separate genes. FakA provides the ... Full text Cite

Discovery of novel bacterial elongation condensing enzyme inhibitors by virtual screening.

Journal Article Bioorg Med Chem Lett · June 1, 2014 The elongation condensing enzymes in the bacterial fatty acid biosynthesis pathway represent desirable targets for the design of novel, broad-spectrum antimicrobial agents. A series of substituted benzoxazolinones was identified in this study as a novel cl ... Full text Link to item Cite

Incorporation of extracellular fatty acids by a fatty acid kinase-dependent pathway in Staphylococcus aureus.

Journal Article Molecular microbiology · April 2014 Acyl-CoA and acyl-acyl carrier protein (ACP) synthetases activate exogenous fatty acids for incorporation into phospholipids in Gram-negative bacteria. However, Gram-positive bacteria utilize an acyltransferase pathway for the biogenesis of phosphatidic ac ... Full text Cite

Phosphatidylglycerol homeostasis in glycerol-phosphate auxotrophs of Staphylococcus aureus.

Journal Article BMC microbiology · November 2013 BackgroundThe balanced synthesis of membrane phospholipids, fatty acids and cell wall constituents is a vital facet of bacterial physiology, but there is little known about the biochemical control points that coordinate these activities in Gram-po ... Full text Cite

Staphylococcus aureus fatty acid auxotrophs do not proliferate in mice.

Journal Article Antimicrobial agents and chemotherapy · November 2013 Inactivation of acetyl-coenzyme A (acetyl-CoA) carboxylase confers resistance to fatty acid synthesis inhibitors in Staphylococcus aureus on media supplemented with fatty acids. The addition of anteiso-fatty acids (1 mM) plus lipoic acid supports normal gr ... Full text Cite

Bacterial lipids: metabolism and membrane homeostasis.

Journal Article Progress in lipid research · July 2013 Membrane lipid homeostasis is a vital facet of bacterial cell physiology. For decades, research in bacterial lipid synthesis was largely confined to the Escherichia coli model system. This basic research provided a blueprint for the biochemistry of lipid m ... Full text Cite

Perturbation of Staphylococcus aureus gene expression by the enoyl-acyl carrier protein reductase inhibitor AFN-1252.

Journal Article Antimicrobial agents and chemotherapy · May 2013 This study examines the alteration in Staphylococcus aureus gene expression following treatment with the type 2 fatty acid synthesis inhibitor AFN-1252. An Affymetrix array study showed that AFN-1252 rapidly increased the expression of fatty acid synthetic ... Full text Cite

Membrane disruption by antimicrobial fatty acids releases low-molecular-weight proteins from Staphylococcus aureus.

Journal Article Journal of bacteriology · October 2012 The skin represents an important barrier for pathogens and is known to produce fatty acids that are toxic toward gram-positive bacteria. A screen of fatty acids as growth inhibitors of Staphylococcus aureus revealed structure-specific antibacterial activit ... Full text Cite

Is bacterial fatty acid synthesis a valid target for antibacterial drug discovery?

Journal Article Current opinion in microbiology · October 2011 The emergence of resistance against most current drugs emphasizes the need to develop new approaches to control bacterial pathogens, particularly Staphylococcus aureus. Bacterial fatty acid synthesis is one such target that is being actively pursued by sev ... Full text Cite

Metabolic basis for the differential susceptibility of Gram-positive pathogens to fatty acid synthesis inhibitors.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · September 2011 The rationale for the pursuit of bacterial type 2 fatty acid synthesis (FASII) as a target for antibacterial drug discovery in Gram-positive organisms is being debated vigorously based on their ability to incorporate extracellular fatty acids. The regulati ... Full text Cite

Characterisation of PduS, the pdu metabolosome corrin reductase, and evidence of substructural organisation within the bacterial microcompartment.

Journal Article PLoS One · November 16, 2010 PduS is a corrin reductase and is required for the reactivation of the cobalamin-dependent diol dehydratase. It is one component encoded within the large propanediol utilisation (pdu) operon, which is responsible for the catabolism of 1,2-propanediol withi ... Full text Link to item Cite

Synthesis of empty bacterial microcompartments, directed organelle protein incorporation, and evidence of filament-associated organelle movement.

Journal Article Molecular cell · April 2010 Compartmentalization is an important process, since it allows the segregation of metabolic activities and, in the era of synthetic biology, represents an important tool by which defined microenvironments can be created for specific metabolic functions. Ind ... Full text Cite

Structure of a trimeric bacterial microcompartment shell protein, EtuB, associated with ethanol utilization in Clostridium kluyveri.

Journal Article The Biochemical journal · September 2009 It has been suggested that ethanol metabolism in the strict anaerobe Clostridium kluyveri occurs within a metabolosome, a subcellular proteinaceous bacterial microcompartment. Two bacterial microcompartment shell proteins [EtuA (ethanol utilization shell p ... Full text Cite

Lactobacillus reuteri DSM 20016 produces cobalamin-dependent diol dehydratase in metabolosomes and metabolizes 1,2-propanediol by disproportionation.

Journal Article Journal of bacteriology · July 2008 A Lactobacillus reuteri strain isolated from sourdough is known to produce the vitamin cobalamin. The organism requires this for glycerol cofermentation by a cobalamin-dependent enzyme, usually termed glycerol dehydratase, in the synthesis of the antimicro ... Full text Cite

Biochemical and structural insights into bacterial organelle form and biogenesis.

Journal Article The Journal of biological chemistry · May 2008 Many heterotrophic bacteria have the ability to make polyhedral structures containing metabolic enzymes that are bounded by a unilamellar protein shell (metabolosomes or enterosomes). These bacterial organelles contain enzymes associated with a specific me ... Full text Cite