Kat Holt
@katholt.bsky.social
Scientist… pathogen genomics & antimicrobial resistance, computational biology & infectious disease epidemiology.
Co-Director LSHTM AMR Centre @lshtmamrcentre.bsky.social
holtlab.net | klebnet.org | typhoidgenomics.org | amr.lshtm.ac.uk
Co-Director LSHTM AMR Centre @lshtmamrcentre.bsky.social
holtlab.net | klebnet.org | typhoidgenomics.org | amr.lshtm.ac.uk
Huge thanks to the 82 (!) coauthors involved in this study, including study teams for BARNARDS, MBIRA, NeoBAC, Baby GERMS-SA, NeoOBS India, NIMBI, GBS-COP and the teams at MLW, CHRF and Aga Khan University Laboratory Network.
Most are not on bluesky (yet!)…
Most are not on bluesky (yet!)…
July 1, 2025 at 9:56 AM
Huge thanks to the 82 (!) coauthors involved in this study, including study teams for BARNARDS, MBIRA, NeoBAC, Baby GERMS-SA, NeoOBS India, NIMBI, GBS-COP and the teams at MLW, CHRF and Aga Khan University Laboratory Network.
Most are not on bluesky (yet!)…
Most are not on bluesky (yet!)…
All the data in the paper is available to explore interactively in an online app, developed by the wonderful @tomstantonmicro.bsky.social klebsiella.shinyapps.io/neonatal/
July 1, 2025 at 9:54 AM
All the data in the paper is available to explore interactively in an online app, developed by the wonderful @tomstantonmicro.bsky.social klebsiella.shinyapps.io/neonatal/
We did also look at O type distribution… there are far fewer types, and the top 5 account for 86% of neonatal sepsis, but it’s unclear how well O-based vaccines can protect against infection.
July 1, 2025 at 9:53 AM
We did also look at O type distribution… there are far fewer types, and the top 5 account for 86% of neonatal sepsis, but it’s unclear how well O-based vaccines can protect against infection.
A lot of sepsis cases are caused by bacterial outbreaks in neonatal units, which can hugely skew the estimated antigen prevalence. So we adjust for localised clustering at each site, to reduce this bias in our prevalence estimates. Turns out this makes a big difference to estimates for some K types.
July 1, 2025 at 9:50 AM
A lot of sepsis cases are caused by bacterial outbreaks in neonatal units, which can hugely skew the estimated antigen prevalence. So we adjust for localised clustering at each site, to reduce this bias in our prevalence estimates. Turns out this makes a big difference to estimates for some K types.
By choosing the top K types in each region, we get a set of 20 antigens that could in principle cover 70% of cases in all our target regions (South Asia and Eastern, Southern, and Western Africa).
Yes this is a lot of antigens! But it has been done for Streptococcus pneumoniae.
Yes this is a lot of antigens! But it has been done for Streptococcus pneumoniae.
July 1, 2025 at 9:50 AM
By choosing the top K types in each region, we get a set of 20 antigens that could in principle cover 70% of cases in all our target regions (South Asia and Eastern, Southern, and Western Africa).
Yes this is a lot of antigens! But it has been done for Streptococcus pneumoniae.
Yes this is a lot of antigens! But it has been done for Streptococcus pneumoniae.
Long story short, we estimate the top 5 K types alone would cover almost 50% of neonatal sepsis cases, but K types vary regionally and so coverage would vary regionally too.
July 1, 2025 at 9:49 AM
Long story short, we estimate the top 5 K types alone would cover almost 50% of neonatal sepsis cases, but K types vary regionally and so coverage would vary regionally too.
We brought together teams from 13 neonatal sepsis surveillance studies, conducted across 35 sites in South Asia and Africa, to pool data and estimate prevalence of capsule and O types amongst #Klebsiella pneumoniae causing sepsis in newborns, using Bayesian modelling.
July 1, 2025 at 9:47 AM
We brought together teams from 13 neonatal sepsis surveillance studies, conducted across 35 sites in South Asia and Africa, to pool data and estimate prevalence of capsule and O types amongst #Klebsiella pneumoniae causing sepsis in newborns, using Bayesian modelling.
The ESGEM-AMR subgroups have been busy encoding AMRrules for lots of pathogens - the beta release has core gene rules for all the ESKAPEE pathogens, plus Salmonella & Yersinia.
May 22, 2025 at 9:38 AM
The ESGEM-AMR subgroups have been busy encoding AMRrules for lots of pathogens - the beta release has core gene rules for all the ESKAPEE pathogens, plus Salmonella & Yersinia.
AMRrules tells us how to interpret these, and our Python package can apply the rules to annotate your AMRfinderplus output with these interpretations.
May 22, 2025 at 9:37 AM
AMRrules tells us how to interpret these, and our Python package can apply the rules to annotate your AMRfinderplus output with these interpretations.
The AMRrules beta release focuses on core genes. These are reported by AMRfinderplus and other tools, but don’t all confer clinical resistance.
May 22, 2025 at 9:37 AM
The AMRrules beta release focuses on core genes. These are reported by AMRfinderplus and other tools, but don’t all confer clinical resistance.
AMRrules encode organism-specific rules for interpreting AMR genotype calls: if I find this gene/mutation in this organism, what does it mean for clinical resistance?
May 22, 2025 at 9:36 AM
AMRrules encode organism-specific rules for interpreting AMR genotype calls: if I find this gene/mutation in this organism, what does it mean for clinical resistance?
Excited to share the first beta release of AMRrules at #ABPHM! (Poster 42 tonight)
interpretamr.github.io/AMRrules
interpretamr.github.io/AMRrules
May 22, 2025 at 9:35 AM
Excited to share the first beta release of AMRrules at #ABPHM! (Poster 42 tonight)
interpretamr.github.io/AMRrules
interpretamr.github.io/AMRrules
Super talk from @efosternyarko.bsky.social @lshtmamrcentre.bsky.social on nanopore based sequencing of cholera across Africa, with PulseNet Africa partners
#ABPHM25
www.biorxiv.org/content/10.1...
#ABPHM25
www.biorxiv.org/content/10.1...
May 21, 2025 at 2:03 PM
Super talk from @efosternyarko.bsky.social @lshtmamrcentre.bsky.social on nanopore based sequencing of cholera across Africa, with PulseNet Africa partners
#ABPHM25
www.biorxiv.org/content/10.1...
#ABPHM25
www.biorxiv.org/content/10.1...
First rose to bloom in our garden this spring, inspired the 4yo to draw this at nursery 🥰
May 17, 2025 at 7:14 PM
First rose to bloom in our garden this spring, inspired the 4yo to draw this at nursery 🥰
In case you’re not Australian, and therefore have no idea wtf a Bin Chicken is 😂
November 26, 2024 at 9:26 PM
In case you’re not Australian, and therefore have no idea wtf a Bin Chicken is 😂
Kleborate v3 is also out now, it calls Kaptive v3 for rapid serotype prediction, plus speciation, MLST, AMR and virulence genotyping. (V3 is also now available via Pathogenwatch and Bactopia) - so get Kleborating! #KLEBS24
November 20, 2024 at 6:12 PM
Kleborate v3 is also out now, it calls Kaptive v3 for rapid serotype prediction, plus speciation, MLST, AMR and virulence genotyping. (V3 is also now available via Pathogenwatch and Bactopia) - so get Kleborating! #KLEBS24
Kaptive v3 is out! It’s much faster than the old version, with improved typeability of K and O loci from low quality draft genomes. Go see Tom’s poster at #KLEBS24!
November 20, 2024 at 5:06 PM
Kaptive v3 is out! It’s much faster than the old version, with improved typeability of K and O loci from low quality draft genomes. Go see Tom’s poster at #KLEBS24!
In 2016, Anna Sheppard and Amy Mathers published this iconic paper on KPC plasmids in a Virginia hospital: “Nested Russian Doll-Like Genetic Mobility Drives Rapid Dissemination of the Carbapenem Resistance Gene blaKPC”
pubmed.ncbi.nlm.nih.gov/27067320/
pubmed.ncbi.nlm.nih.gov/27067320/
November 20, 2024 at 1:05 PM
In 2016, Anna Sheppard and Amy Mathers published this iconic paper on KPC plasmids in a Virginia hospital: “Nested Russian Doll-Like Genetic Mobility Drives Rapid Dissemination of the Carbapenem Resistance Gene blaKPC”
pubmed.ncbi.nlm.nih.gov/27067320/
pubmed.ncbi.nlm.nih.gov/27067320/
In 2015, we published this paper looking at genomic diversity across 300 global Kpn strains from human and animal sources
pubmed.ncbi.nlm.nih.gov/26100894/
pubmed.ncbi.nlm.nih.gov/26100894/
November 20, 2024 at 1:05 PM
In 2015, we published this paper looking at genomic diversity across 300 global Kpn strains from human and animal sources
pubmed.ncbi.nlm.nih.gov/26100894/
pubmed.ncbi.nlm.nih.gov/26100894/
Also in 2014, this key paper identifying capsule variant lineages of Kleb ST258: “Epidemic Klebsiella pneumoniae ST258 is a hybrid strain”
pubmed.ncbi.nlm.nih.gov/24961694/
…and the introduction of core-genome MLST for Klebsiella
pubmed.ncbi.nlm.nih.gov/25341126/
pubmed.ncbi.nlm.nih.gov/24961694/
…and the introduction of core-genome MLST for Klebsiella
pubmed.ncbi.nlm.nih.gov/25341126/
November 20, 2024 at 1:04 PM
Also in 2014, this key paper identifying capsule variant lineages of Kleb ST258: “Epidemic Klebsiella pneumoniae ST258 is a hybrid strain”
pubmed.ncbi.nlm.nih.gov/24961694/
…and the introduction of core-genome MLST for Klebsiella
pubmed.ncbi.nlm.nih.gov/25341126/
pubmed.ncbi.nlm.nih.gov/24961694/
…and the introduction of core-genome MLST for Klebsiella
pubmed.ncbi.nlm.nih.gov/25341126/
First genomic outbreak investigation of #Klebsiella - KPC ST258 in Bethesda, US. Beautiful work from Julie Segre and Evan Snitkin (2012)
pubmed.ncbi.nlm.nih.gov/22914622/
…followed closely by the first study tracking KPC plasmid transfer in the hospital (2014)
pubmed.ncbi.nlm.nih.gov/25232178/
pubmed.ncbi.nlm.nih.gov/22914622/
…followed closely by the first study tracking KPC plasmid transfer in the hospital (2014)
pubmed.ncbi.nlm.nih.gov/25232178/
November 20, 2024 at 1:04 PM
First genomic outbreak investigation of #Klebsiella - KPC ST258 in Bethesda, US. Beautiful work from Julie Segre and Evan Snitkin (2012)
pubmed.ncbi.nlm.nih.gov/22914622/
…followed closely by the first study tracking KPC plasmid transfer in the hospital (2014)
pubmed.ncbi.nlm.nih.gov/25232178/
pubmed.ncbi.nlm.nih.gov/22914622/
…followed closely by the first study tracking KPC plasmid transfer in the hospital (2014)
pubmed.ncbi.nlm.nih.gov/25232178/
A small history lesson in #Klebsiella genomics in honour of #KLEBS24…
2009 was a big year for Klebs!
- First genome published
- First description of ST258 KPC-producing clone
pubmed.ncbi.nlm.nih.gov/19218573/
- First description of NDM-1 beta-lactamase
pubmed.ncbi.nlm.nih.gov/19770275/
2009 was a big year for Klebs!
- First genome published
- First description of ST258 KPC-producing clone
pubmed.ncbi.nlm.nih.gov/19218573/
- First description of NDM-1 beta-lactamase
pubmed.ncbi.nlm.nih.gov/19770275/
November 20, 2024 at 1:03 PM
A small history lesson in #Klebsiella genomics in honour of #KLEBS24…
2009 was a big year for Klebs!
- First genome published
- First description of ST258 KPC-producing clone
pubmed.ncbi.nlm.nih.gov/19218573/
- First description of NDM-1 beta-lactamase
pubmed.ncbi.nlm.nih.gov/19770275/
2009 was a big year for Klebs!
- First genome published
- First description of ST258 KPC-producing clone
pubmed.ncbi.nlm.nih.gov/19218573/
- First description of NDM-1 beta-lactamase
pubmed.ncbi.nlm.nih.gov/19770275/
If you know a lot about AMR mechanisms in a bacterial pathogen, consider joining us in ESGEM-AMR to share your expertise and develop #AMRrules for interpreting resistance-related genotypes in your favourite bug. bit.ly/AMRrules
April 29, 2024 at 4:46 PM
If you know a lot about AMR mechanisms in a bacterial pathogen, consider joining us in ESGEM-AMR to share your expertise and develop #AMRrules for interpreting resistance-related genotypes in your favourite bug. bit.ly/AMRrules
ESGEM, the ESCMID Study Group on Epidemiological Markers is launching a working group to develop standards for interpreting AMR genotypes. Much like EUCAST guidance for interpreting lab phenotypes as S/I/R, we want to define the AMRrules for interpreting genotypes.
April 29, 2024 at 4:45 PM
ESGEM, the ESCMID Study Group on Epidemiological Markers is launching a working group to develop standards for interpreting AMR genotypes. Much like EUCAST guidance for interpreting lab phenotypes as S/I/R, we want to define the AMRrules for interpreting genotypes.
My 2 cents: We're used to using COVID sequencing to break down case numbers into individual variants, which differ in terms of transmissibility, severity and vaccine escape 🦠🧬
We need to do the same for AMR, to dig below species level and understand which variants are high-risk for transmission 🧫🧬
We need to do the same for AMR, to dig below species level and understand which variants are high-risk for transmission 🧫🧬
November 22, 2023 at 11:34 AM
My 2 cents: We're used to using COVID sequencing to break down case numbers into individual variants, which differ in terms of transmissibility, severity and vaccine escape 🦠🧬
We need to do the same for AMR, to dig below species level and understand which variants are high-risk for transmission 🧫🧬
We need to do the same for AMR, to dig below species level and understand which variants are high-risk for transmission 🧫🧬