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Targeting Mnh1 alongside antibiotics may help eliminate this hard-to-reach reservoir.

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Knocking down mnhB reduced early phagocytic uptake and intracellular bacterial burden. Importantly, the phenotype held across three distinct S. aureus lineages. Excitingly, when mnhB was depleted, levofloxacin cleared intracellular bacteria more effectively.

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The intracellular and extracellular fitness landscapes separated clearly. The screen recovered known virulence factors and uncovered new genes specifically needed inside phagocytes. Among them: mnhB, part of the Mnh1 cation–proton antiporter.

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To find the genes behind this lifestyle, we built a genome-wide CRISPRi-seq screen targeting 2,865 S. aureus genes in a THP-1 co-infection model, then compared intracellular and extracellular fitness. @veeninglab.com @vincentdebakker.bsky.social

Jan-Willem Veening @veeninglab.com · 17/06/2026

Why look inside cells? Although S. aureus is mainly extracellular, it can persist within monocytes and macrophages. We found that internalization markedly increased antibiotic survival, making the intracellular niche a potential reservoir for treatment failure.

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Very interesting that nasal epithelial cells show pneumococcal-specific immune dampening and complete absence of CXCL2 and NFKBIA induction. #MicroSky

Jan-Willem Veening @veeninglab.com · 17/06/2026

This work also predicted and showed that epetraborole is a really good antibiotic in the context of pneumococcal meningitis (in the zebrafish). Congratulations to all authors and collaborators!

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Jan-Willem Veening @veeninglab.com · 17/06/2026

This revealed that metabolic adaptation, cell-envelope maintenance, and the oxidative stress response are central to pneumococcal survival in the zebrafish central nervous system.

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Jan-Willem Veening @veeninglab.com · 04/05/2026

Pretty cool, 2 different PREreviews @prereview.bsky.social on our (mainly @camiloperezc6h6.bsky.social's lab) preprint of the structure of the pneumococcal teichoic acid flippase TacF: www.biorxiv.org/content/10.6...

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Jan-Willem Veening @veeninglab.com · 01/05/2026

Congratulations to Jessica for a fantastic PhD defense with maximum score 6/6! Many thanks also to the committee @hingmer.bsky.social Petr Broz Richard Benton @unil.bsky.social @fbm-unil.bsky.social @dmf-unil.bsky.social

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Jan-Willem Veening @veeninglab.com · 09/03/2026

Triple labeled Streptococcus salivarius

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Jan-Willem Veening @veeninglab.com · 13/02/2026

Cool preprint with impressive pneumococcal scRNA-seq data from the Isberg-Cooper-vanOpijnen-Rosch teams. On my reading list: www.biorxiv.org/content/10.6...

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Jan-Willem Veening @veeninglab.com · 25/11/2025

We identified FasR for Fatty Acid Saturation Regulator (SPV_0647) as a transcriptional regulator that maintains proper saturated:unsaturated fatty acid balance, critical during heat stress, by mediating transcription of fabM.

Jan-Willem Veening @veeninglab.com · 25/11/2025

Pneumo prefers GlcNAC over glucose through ManLMN.

Jan-Willem Veening @veeninglab.com · 25/11/2025

We used a multi-omics approach: RNA-seq, proteomics, lipidomics and essentialomics (CRISPRi-seq) on pneumococci grown in different infection mimicking conditions. Some surprises (or not) were that differential gene expression does not correlated with differential gene fitness.

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Jan-Willem Veening @veeninglab.com · 03/09/2025

It will be interesting to test whether induction of RipA leads to stalled replication and subsequent increased comCDE copy numbers and that this is the mechanism for triggered competence. Seems like a simple experiment but they don't like this hypothesis for some reason 🤷‍♂️

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Jan-Willem Veening @veeninglab.com · 08/08/2025

Tour de force paper by Jingren Zhang's group @tsinghuauniversity.bsky.social showing a complex link between peptidoglycan acetylation and phase variation through nutrient sensing #MicroSky journals.plos.org/plospathogen...

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Jan-Willem Veening @veeninglab.com · 07/08/2025

Of course, we ( @axeljanssen.bsky.social) setup a genome browser with a track with sgRNA target sites for easy target validation and gene hunting

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Jan-Willem Veening @veeninglab.com · 07/08/2025

Great collaboration with the lab of Junkal Garmendia, spearheaded by Celia and Johann. First we setup CRISPRi for this bacterium and then generated a genome-wide sgRNA library that allows us to do CRISPRi-seq.

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Jan-Willem Veening @veeninglab.com · 21/11/2024

Great review by @pinholab.bsky.social and Simon Foster on the current knowledge regarding growth, elongation and division of Staphylococcus aureus www.annualreviews.org/content/jour...

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The work supports a model in which the S protein activates PBP1a at sites of cell wall damage. PgdA then deacetylates the newly synthesized PG making the cell wall once again resistant to antimicrobial attack. In absence of the S protein, the complex remains stuck leading to cell death

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S protein mutants are also more sensitive to host-derived antimicrobials such as lysozyme and LL-37 and are attenuated in a zebrafish meningitis and mouse pneumonia infection model.

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In absence of the S protein, a smaller proportion of PBP1a molecules move circumferentially and cells are consequently misshapen and more sensitive to cell wall damage and antibiotics.

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We show that the pneumococcal S protein regulates the activity of the class A penicillin binding protein PBP1a and is in a complex with the peptidoglycan (PG) modifying enzyme PgdA (and interacts with several other proteins such as GpsB and MpgA). Also nice colocalization with PBP1a and PgdA.

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This project started already in 2014 when Clement GFP tagged all hypothetical proteins in S.pneumoniae and we found that this enigmatic LysM-domain containing protein, now called the S protein, was midcell localized through its TM domain. Its also at mid-cell in Streptococcus salivarius.

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Bacitracin/levofloxacin combination therapy was also effective in vivo and improved the treatment of fluoroquinolone-resistant S. pneumoniae infection in a zebrafish meningitis model.

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Activating the LiaR-regulon by the cell envelope-targeting antibiotic bacitracin synergized with ciprofloxacin and levofloxacin. This synergistic antibiotic combination restored sensitivity in fluoroquinolone-resistant strains in vitro.

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This makes LiaS unable to dephosphorylate LiaR. LiaR then activates its regulon. This model makes sense physiologically for a membrane homeostasis sensing system as upon membrane damage the system does not require an intact phosphotransfer reaction, which might be compromised

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Surprisingly, downregulation of liaS caused fluoroquinolone hypersensitivity. LiaS is part of the LiaFSR (VraTSR) three-component regulatory system involved in cell envelope homeostasis. We show that LiaS keeps the response regulator LiaR inactive.

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Jan-Willem Veening @veeninglab.com · 28/09/2024

These profiles show a very specific gene essentiality signature shared between 3 different fluoroquinolones; levo-, cipro- and moxifloxacin, something not seen with Tn-seq or RNA-seq approaches. Not surprisingly, genes involved in DNA repair become more essential.

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Superresolution microscopy (SIM, PALM), ChIP-seq, Hi-C, Streptococcus pneumoniae. What’s not to like?! Many thanks also to (then) MSc students Jasper&Barbara. Project started years ago in Groningen and brilliantly completed by Maria Vittoria

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Jan-Willem Veening @veeninglab.com · 17/08/2024

Most genes are not essential in any given bacteria under any given condition. This makes it hard to assign function to genes. Uncovering genetic interactions such as synthetic lethal (negative) GIs is a great way to figure out what a gene does. Here comes dual CRISPRi-seq!