Shared posts

05 Feb 12:45

Commensal Staphylococcus epidermidis contributes to skin barrier homeostasis by generating protective ceramides

by Yue Zheng, Rachelle L. Hunt, Amer E. Villaruz, Emilie L. Fisher, Ryan Liu, Qian Liu, Gordon Y.C. Cheung, Min Li, Michael Otto
Ceramides are a key constituent of the skin barrier that prevent skin dehydration and aging. Zheng et al. show that the abundant skin commensal Staphylococcus epidermidis secretes a sphingomyelinase that facilitates host production of ceramides to help maintain skin integrity and prevent water loss of damaged skin.
11 Jan 14:00

Direct antimicrobial resistance prediction from clinical MALDI-TOF mass spectra using machine learning

by Caroline Weis

Nature Medicine, Published online: 10 January 2022; doi:10.1038/s41591-021-01619-9

A machine learning method speeds antimicrobial resistance determination to help tailor treatment decisions.
05 Jan 23:48

A naturally inspired antibiotic to target multidrug-resistant pathogens

by Zongqiang Wang

Nature, Published online: 05 January 2022; doi:10.1038/s41586-021-04264-x

The discovery and synthesis of a colistin congener provide a promising clinical lead against mcr-1-encoding colistin-resistant pathogens, which are responsible for an increasing number of deaths from antibiotic-resistant infections.
04 Jan 14:34

Close-up with a parasite that can blind

by Chris Woolston

Nature, Published online: 04 January 2022; doi:10.1038/d41586-021-03823-6

At the Pasteur Institute of Montevideo, María Eugenia Francia tackles a cause of vision problems in babies.
04 Jan 12:47

[ASAP] Development of Photolenalidomide for Cellular Target Identification

by Zhi Lin, Yuka Amako, Farah Kabir, Hope A. Flaxman, Bogdan Budnik, and Christina M. Woo

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Journal of the American Chemical Society
DOI: 10.1021/jacs.1c11920
24 Dec 17:42

Identification of structurally diverse menaquinone-binding antibiotics with in vivo activity against multidrug-resistant pathogens

by Lei Li

Nature Microbiology, Published online: 23 December 2021; doi:10.1038/s41564-021-01013-8

(Meta)genomic mining, bioinformatic prediction and chemical synthesis reveal biosynthetic gene clusters encoding structurally new menaquinone-binding antibiotics that are active against multidrug-resistant Staphylococcus aureus in vivo and Mycobacterium tuberculosis in vitro.
09 Dec 00:28

[ASAP] Emerging Roles of Glycopeptide Antibiotics: Moving beyond Gram-Positive Bacteria

by Yash Acharya, Shaown Bhattacharyya, Geetika Dhanda, and Jayanta Haldar

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ACS Infectious Diseases
DOI: 10.1021/acsinfecdis.1c00367
07 Dec 17:53

Rapid pathogen-specific recruitment of immune effector cells in the skin by secreted toxins

by Thuan H. Nguyen

Nature Microbiology, Published online: 06 December 2021; doi:10.1038/s41564-021-01012-9

Staphylococcus aureus phenol-soluble modulin toxins trigger a fast immune response that involves recruitment of leucocytes to the site of infection via the transcription factor EGR1.
25 Oct 13:39

Hormone-producing bacteria drive prostate cancer

by Karen O’Leary

Nature Medicine, Published online: 25 October 2021; doi:10.1038/d41591-021-00065-x

During androgen-deprivation therapy, certain bacteria in the gut can synthesize androgens, thereby promoting tumor progression and therapy resistance.
25 Oct 13:39

Antibiotic-chemoattractants enhance neutrophil clearance of Staphylococcus aureus

by Jennifer A. E. Payne

Nature Communications, Published online: 25 October 2021; doi:10.1038/s41467-021-26244-5

Antibiotic resistance in Staphylococcus aureus is associated with reduced neutrophil recruitment. Here, Payne et al. link formylated peptides, which act as chemoattractants for neutrophils, with the antibiotic vancomycin and show that these hybrid compounds improve clearance of S. aureus by neutrophils.
21 Oct 17:10

Proteomic analysis of the host–pathogen interface in experimental cholera

by Abdelrahim Zoued

Nature Chemical Biology, Published online: 21 October 2021; doi:10.1038/s41589-021-00894-4

Surface protein tagging and mass spectrometry-based proteomics applied in a rabbit cholera model system identifies proteins involved in Vibrio cholera-host cell interactions and defines a cholera toxin-dependent role for host surfactant protein D.
20 Oct 23:27

[ASAP] Conjugation of Aztreonam, a Synthetic Monocyclic β-Lactam Antibiotic, to a Siderophore Mimetic Significantly Expands Activity Against Gram-Negative Bacteria

by Rui Liu, Patricia A. Miller, and Marvin J. Miller

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ACS Infectious Diseases
DOI: 10.1021/acsinfecdis.1c00458
13 Oct 15:09

Cyclic CMP and cyclic UMP mediate bacterial immunity against phages

by Nitzan Tal, Benjamin R. Morehouse, Adi Millman, Avigail Stokar-Avihail, Carmel Avraham, Taya Fedorenko, Erez Yirmiya, Ehud Herbst, Alexander Brandis, Tevie Mehlman, Yaara Oppenheimer-Shaanan, Alexander F.A. Keszei, Sichen Shao, Gil Amitai, Philip J. Kranzusch, Rotem Sorek
The cyclic pyrimidines cCMP and cUMP serve as second messengers to activate antiviral immunity in bacteria.
08 Oct 16:41

[ASAP] Exploitation of a Klebsiella Bacteriophage Receptor-Binding Protein as a Superior Biorecognition Molecule

by Catarina L. Nogueira, Diana P. Pires, Rodrigo Monteiro, Sílvio B. Santos, and Carla M. Carvalho

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ACS Infectious Diseases
DOI: 10.1021/acsinfecdis.1c00366
07 Oct 12:39

Role of bile acids and gut bacteria in healthy ageing of centenarians

by Bipin Rimal

Nature, Published online: 06 October 2021; doi:10.1038/d41586-021-02196-0

A study in humans indicates that certain bile acids that are produced by bacteria and commonly found in people over 100 boost gut health and protect against infection. These findings shed light on the contributors to healthy ageing.
06 Oct 19:21

A single sulfatase is required to access colonic mucin by a gut bacterium

by Ana S. Luis

Nature, Published online: 06 October 2021; doi:10.1038/s41586-021-03967-5

A single sulfatase produced by a bacterium found in the human colon is essential for degradation of sulfated O-glycans in secreted mucus.
06 Oct 19:19

A selective antibiotic for Lyme disease

by Nadja Leimer, Xiaoqian Wu, Yu Imai, Madeleine Morrissette, Norman Pitt, Quentin Favre-Godal, Akira Iinishi, Samta Jain, Mariaelena Caboni, Inga V. Leus, Vincent Bonifay, Samantha Niles, Rachel Bargabos, Meghan Ghiglieri, Rachel Corsetti, Megan Krumpoch, Gabriel Fox, Sangkeun Son, Dorota Klepacki, Yury S. Polikanov, Cecily A. Freliech, Julie E. McCarthy, Diane G. Edmondson, Steven J. Norris, Anthony D’Onofrio, Linden T. Hu, Helen I. Zgurskaya, Kim Lewis
The use of broad-spectrum antibiotics to treat specific pathogens can damage the host microbiome and contribute to antibiotic resistance. Hygromycin A is selectively taken up through a nucleoside transporter specific to spirochete bacteria, providing a highly selective antibiotic for spirochete infections, such as Lyme disease.
04 Oct 20:27

[ASAP] Biosynthetic Glycan Labeling

by Victoria M. Marando, Daria E. Kim, Phillip J. Calabretta, Matthew B. Kraft, Bryan D. Bryson, and Laura L. Kiessling

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Journal of the American Chemical Society
DOI: 10.1021/jacs.1c07430
03 Oct 12:53

[ASAP] Covalently Engineered Nanobody Chimeras for Targeted Membrane Protein Degradation

by Heng Zhang, Yu Han, Yuanfan Yang, Feng Lin, Kexin Li, Linghao Kong, Hongxiang Liu, Yongjun Dang, Jian Lin, and Peng R. Chen

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Journal of the American Chemical Society
DOI: 10.1021/jacs.1c08521
01 Oct 18:55

Identification of cell wall synthesis inhibitors active against Mycobacterium tuberculosis by competitive activity-based protein profiling

by Michael Li, Hiren V. Patel, Armand B. Cognetta, Trever C. Smith, Ivy Mallick, Jean-François Cavalier, Mary L. Previti, Stéphane Canaan, Bree B. Aldridge, Benjamin F. Cravatt, Jessica C. Seeliger
Identification and validation of targets are major obstacles in discovering drugs to combat Mycobacterium tuberculosis (Mtb). Here, Li et al. establish a streamlined process to identify Mtb inhibitors and their targets and use a structure-activity series and activity-based protein profiling to distinguish serine hydrolases relevant to inhibitor mode of action.
01 Oct 14:33

[ASAP] Targeted Protein Acetylation in Cells Using Heterobifunctional Molecules

by Wesley W. Wang, Li-Yun Chen, Jacob M. Wozniak, Appaso M. Jadhav, Hayden Anderson, Taylor E. Malone, and Christopher G. Parker

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Journal of the American Chemical Society
DOI: 10.1021/jacs.1c07850
29 Sep 23:24

[ASAP] Heterocycloalkynes Fused to a Heterocyclic Core: Searching for an Island with Optimal Stability-Reactivity Balance

by Natalia A. Danilkina, Anastasia I. Govdi, Alexander F. Khlebnikov, Alexander O. Tikhomirov, Vladimir V. Sharoyko, Andrey A. Shtyrov, Mikhail N. Ryazantsev, Stefan Bräse, and Irina A. Balova

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Journal of the American Chemical Society
DOI: 10.1021/jacs.1c06041
28 Sep 13:27

Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes

by Varun Aggarwala

Nature Microbiology, Published online: 27 September 2021; doi:10.1038/s41564-021-00966-0

Quantification of gut bacterial strains after fecal microbiome transplantation using the Strainer algorithm delineates long-term stable engraftment that explains patient outcomes.
28 Sep 13:25

[ASAP] Chemical Biology Tools for Modulating and Visualizing Gram-Negative Bacterial Surface Polysaccharides

by Meng Zheng, Maggie Zheng, Samuel Epstein, Alexa P. Harnagel, Hanee Kim, and Tania J. Lupoli

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ACS Chemical Biology
DOI: 10.1021/acschembio.1c00341
28 Sep 13:23

[ASAP] Discovery of Novel UDP-N-Acetylglucosamine Acyltransferase (LpxA) Inhibitors with Activity against Pseudomonas aeruginosa

by M. Dominic Ryanα, Alastair L. Parkes, David Corbett, Anthony P. Dickie, Michelle Southey, Ole A. Andersen, Daniel B. Stein, Olivier R. Barbeau, Angelo Sanzone, Pia Thommes, John Barker, Ricky Cain, Christel Compper, Magali Dejob, Alain Dorali, Donnya Etheridge, Sian Evans, Adele Faulkner, Elise Gadouleau, Timothy Gorman, Denes Haase, Maisie Holbrow-Wilshaw, Thomas Krulle, Xianfu Li, Christopher Lumley, Barbara Mertins, Spencer Napier, Rajesh Odedra, Kostas Papadopoulos⋈, Vasileios Roumpelakis, Kate Spear, Emily Trimby⧓, Jennifer Williams, Michael Zahn⧖, Anthony D. Keefe, Ying Zhang, Holly T. Soutter◑, Paolo A. Centrella, Matthew A. Clark, John W. Cuozzo, Christoph E. Dumelin¤, Boer Deng☼, Avery Hunt◎, Eric A. Sigelα, Dawn M. Troast◐, and Boudewijn L. M. DeJonge

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Journal of Medicinal Chemistry
DOI: 10.1021/acs.jmedchem.1c00888
15 Sep 20:22

Rational design of a new antibiotic class for drug-resistant infections

by Thomas F. Durand-Reville

Nature, Published online: 15 September 2021; doi:10.1038/s41586-021-03899-0

A lead-optimization strategy combining porin permeation properties and biochemical potency leads to development of a new class of antibiotic based on broad inhibition of penicillin-binding proteins from Gram-negative bacteria.
13 Sep 10:43

[ASAP] Live-Cell Protein Modification by Boronate-Assisted Hydroxamic Acid Catalysis

by Christopher Adamson, Hidetoshi Kajino, Shigehiro A. Kawashima, Kenzo Yamatsugu, and Motomu Kanai

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Journal of the American Chemical Society
DOI: 10.1021/jacs.1c07060
27 Aug 12:22

Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy

by Griffin, M. E., Espinosa, J., Becker, J. L., Luo, J.-D., Carroll, T. S., Jha, J. K., Fanger, G. R., Hang, H. C.

The antitumor efficacy of cancer immunotherapy can correlate with the presence of certain bacterial species within the gut microbiome. However, many of the molecular mechanisms that influence host response to immunotherapy remain elusive. In this study, we show that members of the bacterial genus Enterococcus improve checkpoint inhibitor immunotherapy in mouse tumor models. Active enterococci express and secrete orthologs of the NlpC/p60 peptidoglycan hydrolase SagA that generate immune-active muropeptides. Expression of SagA in nonprotective E. faecalis was sufficient to promote immunotherapy response, and its activity required the peptidoglycan sensor NOD2. Notably, SagA-engineered probiotics or synthetic muropeptides also augmented anti–PD-L1 antitumor efficacy. Taken together, our data suggest that microbiota species with specialized peptidoglycan remodeling activity and muropeptide-based therapeutics may enhance cancer immunotherapy and could be leveraged as next-generation adjuvants.

23 Aug 13:46

An ester bond underlies the mechanical strength of a pathogen surface protein

by Hai Lei

Nature Communications, Published online: 23 August 2021; doi:10.1038/s41467-021-25425-6

Bacterial surface adhesion proteins are characterized by unusual mechanical properties. Here, the authors use atomic force microscopy-based technique to study a surface-anchoring protein Cpe0147 from Clostridium perfringens and show that an ester bond can withstand considerable mechanical forces and prevent complete protein unfolding.
14 Aug 14:37

[ASAP] Reprogramming of Protein-Targeted Small-Molecule Medicines to RNA by Ribonuclease Recruitment

by Peiyuan Zhang, Xiaohui Liu, Daniel Abegg, Toru Tanaka, Yuquan Tong, Raphael I. Benhamou, Jared Baisden, Gogce Crynen, Samantha M. Meyer, Michael D. Cameron, Arnab K. Chatterjee, Alexander Adibekian, Jessica L. Childs-Disney, and Matthew D. Disney

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Journal of the American Chemical Society
DOI: 10.1021/jacs.1c02248