David Sychantha
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View article: A ubiquitous <i>Streptomyces</i> biosynthetic megacluster encodes an arsenal of synergistic biotin-targeting antibiotics
A ubiquitous <i>Streptomyces</i> biosynthetic megacluster encodes an arsenal of synergistic biotin-targeting antibiotics Open
The rise of multidrug-resistant pathogens underscores the urgent need for antibiotics that act through new targets and mechanisms. Biotin metabolism, essential in most bacteria, remains underexploited therapeutically. Here, we uncover a hi…
View article: Rapidly evolving orphan immunity genes protect human gut bacteria from intoxication by the type VI secretion system
Rapidly evolving orphan immunity genes protect human gut bacteria from intoxication by the type VI secretion system Open
Bacteria encode diverse mechanisms for mediating interbacterial antagonism through the exchange of toxic effector proteins. Although the structure, function, and regulation of these pathways has been well established for many organisms, an…
View article: Perturbation of <i>Pseudomonas aeruginosa</i> peptidoglycan recycling by anti-folates and design of a dual-action inhibitor
Perturbation of <i>Pseudomonas aeruginosa</i> peptidoglycan recycling by anti-folates and design of a dual-action inhibitor Open
Peptidoglycan (PG) is an important bacterial macromolecule that confers cell shape and structural integrity, and is a key antibiotic target. Its synthesis and turnover are carefully coordinated with other cellular processes and pathways. D…
View article: The histidine kinase VraS orchestrates the cell-wall stress response in <i>Staphylococcus aureus</i> via its direct interaction with glycopeptides and β-lactams
The histidine kinase VraS orchestrates the cell-wall stress response in <i>Staphylococcus aureus</i> via its direct interaction with glycopeptides and β-lactams Open
Multidrug-resistant Staphylococcus aureus is a major global health threat, with the VraTSR three-component system playing a key role in sensing and conferring resistance to cell-wall active antibiotics, particularly vancomycin. VraTSR comp…
View article: A microbial natural product fractionation library screen with HRMS/MS dereplication identifies new lipopeptaibiotics against Candida auris
A microbial natural product fractionation library screen with HRMS/MS dereplication identifies new lipopeptaibiotics against Candida auris Open
The rise of drug-resistant fungal pathogens, including Candida auris, highlights the urgent need for novel antifungal therapies. We developed a cost-effective platform combining microbial extract prefractionation with rapid MS/MS-bioinform…
View article: Targeting bacterial nickel transport with aspergillomarasmine A suppresses virulence-associated Ni-dependent enzymes
Targeting bacterial nickel transport with aspergillomarasmine A suppresses virulence-associated Ni-dependent enzymes Open
Microbial Ni 2+ homeostasis underpins the virulence of several clinical pathogens. Ni 2+ is an essential cofactor in urease and [NiFe]-hydrogenases involved in colonization and persistence. Many microbes produce metallophores to sequester …
View article: Synthesis of lipid-linked precursors of the bacterial cell wall is governed by a feedback control mechanism in Pseudomonas aeruginosa
Synthesis of lipid-linked precursors of the bacterial cell wall is governed by a feedback control mechanism in Pseudomonas aeruginosa Open
Many bacterial surface glycans such as the peptidoglycan (PG) cell wall are built from monomeric units linked to a polyprenyl lipid carrier. How this limiting carrier is distributed among competing pathways has remained unclear. Here we de…
View article: Metabolic connections between folate and peptidoglycan pathways in<i>Pseudomonas aeruginosa</i>inform rational design of a dual-action inhibitor
Metabolic connections between folate and peptidoglycan pathways in<i>Pseudomonas aeruginosa</i>inform rational design of a dual-action inhibitor Open
Peptidoglycan is an important bacterial macromolecule that confers cell shape and structural integrity, and a key antibiotic target. The synthesis and turnover of peptidoglycan are carefully coordinated with other cellular processes and pa…
View article: CCDC 2105011: Experimental Crystal Structure Determination
CCDC 2105011: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: A feedback control mechanism governs the synthesis of lipid-linked precursors of the bacterial cell wall
A feedback control mechanism governs the synthesis of lipid-linked precursors of the bacterial cell wall Open
SUMMARY Many bacterial surface glycans such as the peptidoglycan (PG) cell wall, O-antigens, and capsules are built from monomeric units linked to a polyprenyl lipid carrier. How this limiting lipid carrier is effectively distributed among…
View article: Identification of a broadly conserved family of enzymes that hydrolyze (p)ppApp
Identification of a broadly conserved family of enzymes that hydrolyze (p)ppApp Open
Bacteria produce a variety of nucleotide second messengers to adapt to their surroundings. Although chemically similar, the nucleotides guanosine penta- and tetraphosphate [(p)ppGpp] and adenosine penta- and tetraphosphate [(p)ppApp] have …
View article: Three-Dimensional Structure and Optimization of the Metallo-β-Lactamase Inhibitor Aspergillomarasmine A
Three-Dimensional Structure and Optimization of the Metallo-β-Lactamase Inhibitor Aspergillomarasmine A Open
The aminopolycarboxylic acid aspergillomarasmine A (AMA) is a natural Zn2+ metallophore and inhibitor of metallo-β-lactamases (MBLs) which reverses β-lactam resistance. The first crystal structure of an AMA coordination complex is reported…
View article: A widespread family of bacterial gene clusters produces ClpP inhibitors
A widespread family of bacterial gene clusters produces ClpP inhibitors Open
Intracellular proteolytic complexes play an essential role in modeling the proteome in both bacteria and eukaryotes. ClpP is the protease subunit of one such highly conserved proteolytic complex that, despite its potential, remains unexplo…
View article: Biotinylated NDM-1 peptide analysis.mzdata.xml
Biotinylated NDM-1 peptide analysis.mzdata.xml Open
LC MS/MS peptide mapping of biotinylated NDM-1 digested with trypsin and aspN proteases. MS/MS was targeted to the peptide DNITVGIDGTDIAFGGCLIK with the cysteine modified by biotin maleimide (m/z = 1237.11 [M+2H]2+). The neutral mass of th…
View article: Correction: Peptidoglycomics reveals compositional changes in peptidoglycan between biofilm- and planktonic-derived Pseudomonas aeruginosa.
Correction: Peptidoglycomics reveals compositional changes in peptidoglycan between biofilm- and planktonic-derived Pseudomonas aeruginosa. Open
VOLUME 295 (2020) PAGES 504–516 Due to publisher error, the DOI for the mass spectrometry data was incomplete. The complete DOI is 10.6084/m9.figshare.10277909.
View article: Suppression of β-Lactam Resistance by Aspergillomarasmine A Is Influenced by both the Metallo-β-Lactamase Target and the Antibiotic Partner
Suppression of β-Lactam Resistance by Aspergillomarasmine A Is Influenced by both the Metallo-β-Lactamase Target and the Antibiotic Partner Open
The rise of Gram-negative pathogens expressing metallo-β-lactamases (MBLs) is a growing concern, threatening the efficacy of β-lactam antibiotics, in particular, the carbapenems. There are no inhibitors of MBLs in current clinical use. Asp…
View article: Mechanistic Pathways for Peptidoglycan O-Acetylation and De-O-Acetylation
Mechanistic Pathways for Peptidoglycan O-Acetylation and De-O-Acetylation Open
The post-synthetic O-acetylation of the essential component of bacterial cell walls, peptidoglycan (PG), is performed by many pathogenic bacteria to help them evade the lytic action of innate immunity responses. Occurring at the C-6 hydrox…
View article: In vitro characterization of the antivirulence target of Gram-positive pathogens, peptidoglycan O-acetyltransferase A (OatA)
In vitro characterization of the antivirulence target of Gram-positive pathogens, peptidoglycan O-acetyltransferase A (OatA) Open
The O-acetylation of the essential cell wall polymer peptidoglycan occurs in most Gram-positive bacterial pathogens, including species of Staphylococcus, Streptococcus and Enterococcus. This modification to peptidoglycan protects these pat…
View article: O-acetylation of the serine-rich repeat glycoprotein GspB is coordinated with accessory Sec transport
O-acetylation of the serine-rich repeat glycoprotein GspB is coordinated with accessory Sec transport Open
The serine-rich repeat (SRR) glycoproteins are a family of adhesins found in many Gram-positive bacteria. Expression of the SRR adhesins has been linked to virulence for a variety of infections, including streptococcal endocarditis. The SR…