Joe Wanford

Reversible phenotypic resistance to phage infection via capsule downregulation in Klebsiella pneumoniae Molecular biology; Microbiology; Cell biology

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Reversible phenotypic resistance to phage infection via capsule downregulation in Klebsiella pneumoniae
#phage #phageky

www.cell.com/iscience/ful...

Very interesting new protective response in live (!) neutrophils against bacterial infection:

Versatile NTP recognition and domain fusions expand the functional repertoire of the ParB-CTPase fold beyond chromosome segregation | PNAS Nucleotide triphosphate (NTP)-dependent molecular switches regulate essential cellular processes by cycling between active and inactive states thro...

Now published. Thank you very much to our collaborative team, and very supportive editors and reviewers!!!

www.pnas.org/doi/10.1073/...

Differential targeting of human pyroptotic Caspase-5 and Caspase-4 by Shigella OspC2 and OspC3 https://www.biorxiv.org/content/10.64898/2025.12.04.692159v1

Antibiotics accumulate in Klebsiella pneumoniae liver abscesses but fail to eliminate antibiotic-tolerant populations | PNAS Liver abscesses caused by hypervirulent Klebsiella pneumoniae (hvKp) can lead to severe metastatic complications, with mortality rates ranging from...

Thrilled to share our latest paper on antibiotic treatment failure of Klebsiella pneumoniae liver abscesses

www.pnas.org/doi/full/10....

@drwalkermsbanta.bsky.social

Life Identification Numbers: A bacterial strain nomenclature approach Unified strain taxonomies are needed for the epidemiological surveillance of bacterial pathogens and international communication in microbiological research. Core genome multilocus sequence typing (cg...

Huge preprint if you are interested in bacterial strain taxonomy! The why and how of cgMLST LIN codes: An extensively revised and expanded version doi.org/10.1101/2024... I will summarize it for you in this thread 👇

Intracellular competition shapes plasmid population dynamics From populations of multicellular organisms to selfish genetic elements, conflicts between levels of biological organization are central to evolution. Plasmids are extrachromosomal, self-replicating g...

Hot off the press! Our latest paper led by @fernpizza.bsky.social, understanding how plasmids evolve inside cells. These small, self-replicating DNA circles live inside bacteria and carry antibiotic resistance genes, but also compete with one another to replicate. 1/
www.science.org/doi/10.1126/...

figure showing estimated proportion of cases in clusters, for each site. range from 0.04 to 0.93, mean estimate in random effects model is 0.57 [0.46,0.68]

#AMR #Klebsiella cause >100,000 neonatal deaths globally each year.

Our new preprint shows more than half of #Klebsiella pneumoniae neonatal sepsis cases in African and South Asian are nosocomial, acquired through transmission in neonatal units. #WAAW

doi.org/10.1101/2025...

A Novel Technique to Characterize Klebsiella pneumoniae Populations Indicates that Mono-Colonization is Associated with Risk of Infection https://www.biorxiv.org/content/10.1101/2025.11.05.686704v1

Genetic population structure of Haemophilus influenzae at local and global scales - Nature Microbiology Large-scale sequencing and population genomic analyses reveal frequent transmission, a highly admixed global population structure and evidence of pervasive negative selection in Haemophilus influenzae...

Out recently in Nature Microbiology👇

www.nature.com/articles/s41...

Phages use contingency loci as a bet-hedging strategy https://www.biorxiv.org/content/10.1101/2025.10.21.683753v1

Enhanced virulence and stress tolerance are signatures of epidemiologically successful Shigella sonnei
@sydneylmiles.bsky.social @katholt.bsky.social
🙏to transformative collaborative effort

www.nature.com/articles/s41...

Great opportunity in a great lab!

🚨If you want to help us to answer these questions, there’s still time to apply for our open PDRA positions (deadline 21st Sept):

Molecular microbiology/genomics - tinyurl.com/mtrwtx5e
Infection biology - tinyurl.com/2s3u8ca2

So many questions remain:

• What are the dynamics of phase variation in the host?
• In what other contexts is this process important?
• What are the determinants of switching rate, and how does this vary by clonal lineage?
• How can this information inform genomic surveillance?

I want to thank all of my fantastic collaborators their help and support with this work @codendall.bsky.social @neisseriaspanin.bsky.social @margaretlam.bsky.social @katholt.bsky.social @josebengoechea.bsky.social (+ many others not on bluesky)

Comparative genomics revealed that this switch is conserved in all variants of the rmp locus indicating this is likely a key adaptive strategy in all HVKp

The switch - termed 'phase variation' - enables HVKp to both ‘have their cake and eat it’, alternating between states of epithelial cell infection, and survival in human serum :

By combining in vitro infection assays, whole genome sequencing, and molecular microbiology approaches, we demonstrate that a DNA repeat in rmpA functions as a genetic switch between mucoid and non-mucoid phenotypes

Simple Sequence Repeats Mediate Phase Variation of the Mucoid Phenotype in Hypervirulent Klebsiella pneumoniae Hypervirulent Klebsiella pneumoniae (HVKp) express a thick mucoid capsular polysaccharide which is essential for virulence and survival in the bloodstream but inhibits epithelial adhesion and invasion...

🎉 Delighted to share the first pre-print from my lab where we demonstrate that intergenic DNA repeats mediate phase variation of the mucoid phenotype in hypervirulent Klebsiella pneumoniae: www.biorxiv.org/content/10.1... #klebclub

Serotype swapping in Klebsiella spp. by plug-and-play Understanding how complex, multi-gene systems evolve and function across genetic backgrounds is a central question in molecular evolution. While such systems often impose costs through epistatic inter...

How complex functions, with important physiological and evolutionary impacts get repeatedly and efficiently transferred across genomes?
That’s what we explored using one of the fastest-evolving loci in Bacteria: the capsule locus.
The paper: www.biorxiv.org/content/10.1...
Thread👇

Thanks, Jose!

Thanks, Lesley!

Postdoctoral Research Associate in Molecular Microbiology

🚨 Job alert 🚨

I’m recruiting two postdoctoral research associates to join my lab at KCL to study how #Klebsiella pneumoniae regulates virulence factor expression during infection! #klebclub

Mol Micro: tinyurl.com/mtrwtx5e

Infection: tinyurl.com/2s3u8ca2

Deadline: 21st September.

Thanks so much, Lesley :)

Thanks, Julie! The pain of the mocks was worth it 😂

I will shortly be advertising multiple PDRA positions – if you love molecular microbiology and bacterial pathogenesis, please get in touch for a chat!

Now that it’s official, I’m delighted to announce I’ve been awarded a Wellcome Trust Career Development Award to fund my lab’s work on K. pneumoniae pathogenesis for the next 8 years! Very grateful to many fantastic mentors and collaborators who’ve helped throughout this process.

Bifidobacteria support optimal infant vaccine responses - Nature Neonatal antibiotic use is shown to reduce immune response to infant vaccines, accompanied by reduced abundance of Bifidobacteria in the gut microbiota, with experiments in mice indicating that probio...

Delighted our study (7+ years in the making) is out today in Nature. In a nutshell, 48 hours of antibiotics in week 1 led to impaired vaccine responses up to 15 months later in infants. We show (in-vivo) a probiotic can fix it #microbiome #science #immunology
www.nature.com/articles/s41...

I am recruiting a research assistant. Please send to anyone you know who is interested in gaining more lab experience in host:pathogen interactions of bacterial infections.

www.jobs.cam.ac.uk/job/50738/