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Copy number flexibility facilitates heteroresistance to increasing antibiotic pressure and threatens the beta-lactam pipeline

Choby et al. show that dynamic increases in the copy number of preexisting β-lactamase genes in heteroresistance enables resistance of continua of cellular subpopulations, flexibly overcoming enhanced β-lactams without new evolution and threatening the β-lactam pipeline.

Jacob E. Choby
Tugba Ozturk
David S. Weiss
ResearchOpen Access01 Jul 2025
Nature Communications

Volume: 16, P: 1-17
An active site loop toggles between conformations to control antibiotic hydrolysis and inhibition potency for CTX-M β-lactamase drug-resistance enzymes

β-lactamases are a source of antibiotic resistance. Here, the authors show that an active site loop in β-lactamase toggles between conformations that control antibiotic hydrolysis and inhibitor susceptibility, highlighting the role of active site conformations in enzyme activity and inhibition.

Shuo Lu
Liya Hu
Timothy Palzkill
ResearchOpen Access07 Nov 2022
Nature Communications

Volume: 13, P: 1-13
Differential active site requirements for NDM-1 β-lactamase hydrolysis of carbapenem versus penicillin and cephalosporin antibiotics

The NDM-1 β-lactamase confers resistance to most β-lactam antibiotics. By functional analysis of residues required for hydrolysis, Sun et al. reveal stringent sequence constraints for carbapenems, suggesting that specific combinations of NDM-1 inhibitors might help reducing resistance development

Zhizeng Sun
Liya Hu
Timothy Palzkill
ResearchOpen Access30 Oct 2018
Nature Communications

Volume: 9, P: 1-14
DNA-encoded chemical libraries yield non-covalent and non-peptidic SARS-CoV-2 main protease inhibitors

Conventional structure-based design of M^pro inhibitors of SARS-CoV-2 often starts from the structural information of M^pro and their binders; however, the continual rise of resistant strains requires innovative routes to discover new inhibitors. Here, the authors develop a DNA-encoded chemical library screening to produce non-covalent, non-peptidic small molecule inhibitors for SARS-CoV-2 M^pro independently of preliminary knowledge regarding suitable starting points.

Ravikumar Jimmidi
Srinivas Chamakuri
Damian W. Young
ResearchOpen Access04 Aug 2023
Communications Chemistry

Volume: 6, P: 1-10
Norovirus replication, host interactions and vaccine advances

In this Review, the authors highlight recent advances in human norovirus biology, including classification, strain-specific differences in cell entry and innate immune responses. They also highlight progress in virus replication, neutralization assays, structural biology and antiviral targets, as well as the status and challenges of vaccine development.

B. V. Venkataram Prasad
Robert L. Atmar
Mary K. Estes
Reviews17 Jan 2025
Nature Reviews Microbiology

Volume: 23, P: 385-401
Mapping human norovirus antigens during infection reveals the breadth of the humoral immune response

Lynn Su
Wanzhi Huang
Timothy Palzkill
ResearchOpen Access06 Jun 2023
npj Vaccines

Volume: 8, P: 1-15
Mapping the determinants of catalysis and substrate specificity of the antibiotic resistance enzyme CTX-M β-lactamase

Structural analysis, antibiotic selection, and deep sequencing of CTX-M-14 mutants identify residues required for β-lactamase activity.

Allison Judge
Liya Hu
Timothy Palzkill
ResearchOpen Access12 Jan 2023
Communications Biology

Volume: 6, P: 1-11
An autism-linked missense mutation in SHANK3 reveals the modularity of Shank3 function

Li Wang
Kaifang Pang
Huda Y. Zoghbi
Research04 Jan 2019
Molecular Psychiatry

Volume: 25, P: 2534-2555
Deep Sequencing of Random Mutant Libraries Reveals the Active Site of the Narrow Specificity CphA Metallo-β-Lactamase is Fragile to Mutations

Zhizeng Sun
Shrenik C. Mehta
Timothy Palzkill
ResearchOpen Access12 Sept 2016
Scientific Reports

Volume: 6, P: 1-12

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Copy number flexibility facilitates heteroresistance to increasing antibiotic pressure and threatens the beta-lactam pipeline

An active site loop toggles between conformations to control antibiotic hydrolysis and inhibition potency for CTX-M β-lactamase drug-resistance enzymes

Differential active site requirements for NDM-1 β-lactamase hydrolysis of carbapenem versus penicillin and cephalosporin antibiotics

DNA-encoded chemical libraries yield non-covalent and non-peptidic SARS-CoV-2 main protease inhibitors

Norovirus replication, host interactions and vaccine advances

Mapping human norovirus antigens during infection reveals the breadth of the humoral immune response

Mapping the determinants of catalysis and substrate specificity of the antibiotic resistance enzyme CTX-M β-lactamase

An autism-linked missense mutation in SHANK3 reveals the modularity of Shank3 function

Deep Sequencing of Random Mutant Libraries Reveals the Active Site of the Narrow Specificity CphA Metallo-β-Lactamase is Fragile to Mutations

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