Subtopic Deep Dive
Multilocus Sequence Typing of Pathogens
Research Guide
What is Multilocus Sequence Typing of Pathogens?
Multilocus Sequence Typing (MLST) sequences seven housekeeping genes to assign allelic profiles and sequence types (STs) for identifying bacterial pathogen clones.
MLST provides portable, standardized genotyping across labs, as introduced by Maiden et al. (1998) with 3785 citations. PubMLST.org hosts curated MLST databases for over 100 species (Jolley et al., 2018, 3121 citations). It supports epidemiology by tracking clonal complexes like CC17 in Enterococcus faecium (Top et al., 2008).
Why It Matters
MLST tracks antimicrobial-resistant strains in global surveillance, enabling outbreak tracing for pathogens like vancomycin-resistant Enterococcus faecium via CC17 lineage (Top et al., 2008). PubMLST integrates population data for virulence evolution studies (Jolley et al., 2018). It underpins infection control by discriminating isolates in hospital settings (Sabat et al., 2013).
Key Research Challenges
Portability Across Labs
Traditional typing lacks standardization, hindering inter-lab comparisons (Maiden et al., 1998). MLST addresses this via housekeeping gene alleles but requires curated databases. PubMLST standardizes schemes for 100+ species (Jolley et al., 2018).
Genomic Era Resolution
MLST offers moderate resolution compared to whole-genome sequencing (WGS) (Li et al., 2009). WGS detects more variants but demands high compute (Uelze et al., 2020). Hybrid approaches integrate MLST with cgMLST (Deng et al., 2016).
Database Curation Scale
Maintaining allele schemes for emerging pathogens strains resources (Jolley et al., 2018). Manual curation limits speed for outbreaks. Automation via BIGSdb helps but needs validation (Ågren et al., 2012).
Essential Papers
Multilocus sequence typing: A portable approach to the identification of clones within populations of pathogenic microorganisms
Martin Maiden, Jane A. Bygraves, Edward J. Feil et al. · 1998 · Proceedings of the National Academy of Sciences · 3.8K citations
Traditional and molecular typing schemes for the characterization of pathogenic microorganisms are poorly portable because they index variation that is difficult to compare among laboratories. To o...
Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications
Keith A. Jolley, James E. Bray, Martin Maiden · 2018 · Wellcome Open Research · 3.1K citations
<ns4:p>The <ns4:ext-link xmlns:ns3="http://www.w3.org/1999/xlink" ext-link-type="uri" ns3:href="https://pubmlst.org/">PubMLST.org</ns4:ext-link> website hosts a collection of open-access, curated d...
Overview of molecular typing methods for outbreak detection and epidemiological surveillance
A. Sabat, Ana Budimir, D Nashev et al. · 2013 · Eurosurveillance · 535 citations
Typing methods for discriminating different bacterial isolates of the same species are essential epidemiological tools in infection prevention and control. Traditional typing systems based on pheno...
Bacterial strain typing in the genomic era
Wen‐Jun Li, Didier Raoult, Pierre‐Edouard Fournier · 2009 · FEMS Microbiology Reviews · 328 citations
Bacterial strain typing, or identifying bacteria at the strain level, is particularly important for diagnosis, treatment, and epidemiological surveillance of bacterial infections. This is especiall...
Emergence of CC17<i>Enterococcus faecium</i>: from commensal to hospital-adapted pathogen
Janetta Top, Rob J. L. Willems, Marc J. M. Bonten · 2008 · FEMS Immunology & Medical Microbiology · 259 citations
For many years, Enterococcus faecium was considered to be a commensal of the digestive tract, which only sporadically caused opportunistic infections in severely ill patients. Over the last two dec...
Gegenees: Fragmented Alignment of Multiple Genomes for Determining Phylogenomic Distances and Genetic Signatures Unique for Specified Target Groups
Joakim Ågren, Anders Sundström, Therese Håfström et al. · 2012 · PLoS ONE · 252 citations
The rapid development of Next Generation Sequencing technologies leads to the accumulation of huge amounts of sequencing data. The scientific community faces an enormous challenge in how to deal wi...
Fungal infections in animals: a patchwork of different situations
Seyedmojtaba Seyedmousavi, Sandra de Moraes Gimenes Bosco, Sybren de Hoog et al. · 2017 · Medical Mycology · 239 citations
The importance of fungal infections in both human and animals has increased over the last decades. This article represents an overview of the different categories of fungal infections that can be e...
Reading Guide
Foundational Papers
Start with Maiden et al. (1998) for MLST definition and portability; Sabat et al. (2013) for typing methods overview; Top et al. (2008) for clonal complex application in E. faecium.
Recent Advances
Jolley et al. (2018) for PubMLST and BIGSdb; Uelze et al. (2020) for WGS-based typing; Deng et al. (2016) for genomic epidemiology.
Core Methods
Seven housekeeping gene sequencing (Maiden 1998); BIGSdb curation (Jolley 2018); fragmented alignment with Gegenees (Ågren 2012); cgMLST from WGS (Uelze 2020).
How PapersFlow Helps You Research Multilocus Sequence Typing of Pathogens
Discover & Search
Research Agent uses searchPapers('MLST clonal complexes Enterococcus') to find Top et al. (2008), then citationGraph reveals 259 citing papers on hospital-adapted strains, and findSimilarPapers expands to CC17 surveillance.
Analyze & Verify
Analysis Agent runs readPaperContent on Maiden et al. (1998) to extract seven-gene schemes, verifies ST portability claims with CoVe against Jolley et al. (2018), and uses runPythonAnalysis for allele frequency stats with pandas on PubMLST data.
Synthesize & Write
Synthesis Agent detects gaps in MLST vs. WGS resolution (Uelze et al., 2020), flags contradictions in strain typing evolution (Li et al., 2009), while Writing Agent applies latexEditText for methods sections, latexSyncCitations for 50+ refs, and latexCompile for publication-ready manuscripts with exportMermaid for clonal complex diagrams.
Use Cases
"Compute phylogenetic distances from MLST data of E. faecium isolates"
Research Agent → searchPapers → Analysis Agent → runPythonAnalysis (NumPy dendrogram on ST alleles) → matplotlib plot of CC17 tree.
"Draft MLST outbreak report with PubMLST schemes"
Synthesis Agent → gap detection → Writing Agent → latexEditText (methods) → latexSyncCitations (Jolley 2018) → latexCompile → PDF with ST diagrams.
"Find code for Gegenees MLST alignment"
Research Agent → paperExtractUrls (Ågren 2012) → paperFindGithubRepo → githubRepoInspect → export code for phylogenomic distances.
Automated Workflows
Deep Research workflow scans 50+ MLST papers via searchPapers → citationGraph → structured report on clonal evolution (Maiden 1998 to Uelze 2020). DeepScan applies 7-step CoVe to verify PubMLST scheme portability (Jolley 2018). Theorizer generates hypotheses on CC17 emergence from Top et al. (2008) literature synthesis.
Frequently Asked Questions
What is Multilocus Sequence Typing?
MLST assigns sequence types by sequencing seven housekeeping loci and comparing alleles to databases like PubMLST (Maiden et al., 1998).
What are key MLST methods?
Standard MLST uses portable allele profiles; PubMLST hosts BIGSdb for curation; hybrids integrate with WGS (Jolley et al., 2018; Uelze et al., 2020).
What are seminal MLST papers?
Maiden et al. (1998, 3785 citations) introduced MLST; Jolley et al. (2018, 3121 citations) detailed PubMLST; Sabat et al. (2013) overviewed typing for surveillance.
What are open problems in MLST?
Scaling curation for new pathogens; improving resolution vs. WGS; automating phylogenomics from fragmented genomes (Li et al., 2009; Ågren et al., 2012).
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