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Raphael H. Valdivia

Nanaline H. Duke Distinguished Professor of Molecular Genetics and Microbiology
Integrative Immunobiology
4112 MSRB III, Box 3580, Durham, NC 27710
4112 MSRB III Box 3580, 3 Genome Court, Durham, NC 27710

Selected Publications


Mechanism of 2'-fucosyllactose degradation by human-associated Akkermansia.

Journal Article J Bacteriol · February 22, 2024 Among the first microorganisms to colonize the human gut of breastfed infants are bacteria capable of fermenting human milk oligosaccharides (HMOs). One of the most abundant HMOs, 2'-fucosyllactose (2'-FL), may specifically drive bacterial colonization of ... Full text Link to item Cite

The acetylase activity of Cdu1 regulates bacterial exit from infected cells by protecting Chlamydia effectors from degradation

Journal Article eLife · February 15, 2024 Many cellular processes are regulated by ubiquitin-mediated proteasomal degradation. Pathogens can regulate eukaryotic proteolysis through the delivery of proteins with de-ubiquitinating (DUB) activities. The obligate intracellular pathogen Full text Cite

Use of gene sequences as type for naming prokaryotes: Recommendations of the international committee on the taxonomy of chlamydiae

Journal Article New Microbes and New Infections · September 1, 2023 The International Committee on Systematics of Prokaryotes (ICSP) discussed and rejected in 2020 a proposal to modify the International Code of Nomenclature of Prokaryotes to allow the use of gene sequences as type for naming prokaryotes. An alternative nom ... Full text Cite

Spontaneous episodic inflammation in the intestines of mice lacking HNF4A is driven by microbiota and associated with early life microbiota alterations.

Journal Article mBio · August 31, 2023 The inflammatory bowel diseases (IBD) occur in genetically susceptible individuals who mount inappropriate immune responses to their microbiota leading to chronic intestinal inflammation. Whereas IBD clinical presentation is well described, how interaction ... Full text Link to item Cite

The Chlamydia effector CpoS modulates the inclusion microenvironment and restricts the interferon response by acting on Rab35.

Journal Article mBio · August 31, 2023 The obligate intracellular bacterium Chlamydia trachomatis inserts a family of inclusion membrane (Inc) proteins into the membrane of its vacuole (the inclusion). The Inc CpoS is a critical suppressor of host cellular immune surveillance, but the underlyin ... Full text Link to item Cite

The emerging complexity of Chlamydia trachomatis interactions with host cells as revealed by molecular genetic approaches.

Journal Article Curr Opin Microbiol · August 2023 Chlamydia trachomatis (Ct) is an intracellular bacterial pathogen that relies on the activity of secreted proteins known as effectors to promote replication and avoidance of immune clearance. Understanding the contribution of Ct effectors to pathogenesis h ... Full text Link to item Cite

A genetic system for Akkermansia muciniphila reveals a role for mucin foraging in gut colonization and host sterol biosynthesis gene expression.

Journal Article Nat Microbiol · August 2023 Akkermansia muciniphila, a mucophilic member of the gut microbiota, protects its host against metabolic disorders. Because it is genetically intractable, the mechanisms underlying mucin metabolism, gut colonization and its impact on host physiology are not ... Full text Link to item Cite

The bacterial effector GarD shields Chlamydia trachomatis inclusions from RNF213-mediated ubiquitylation and destruction.

Journal Article Cell Host Microbe · December 14, 2022 Chlamydia trachomatis is the leading cause of sexually transmitted bacterial infections and a major threat to women's reproductive health in particular. This obligate intracellular pathogen resides and replicates within a cellular compartment termed an inc ... Full text Link to item Cite

Chlamydia repurposes the actin-binding protein EPS8 to disassemble epithelial tight junctions and promote infection.

Journal Article Cell host & microbe · December 2022 Invasive microbial pathogens often disrupt epithelial barriers, yet the mechanisms used to dismantle tight junctions are poorly understood. Here, we show that the obligate pathogen Chlamydia trachomatis uses the effector protein TepP to transiently disasse ... Full text Cite

Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment.

Journal Article Sci Transl Med · November 16, 2022 Not all patients with cancer and severe neutropenia develop fever, and the fecal microbiome may play a role. In a single-center study of patients undergoing hematopoietic cell transplant (n = 119), the fecal microbiome was characterized at onset of severe ... Full text Link to item Cite

Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease.

Journal Article Cell · September 29, 2022 The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal ... Full text Link to item Cite

Human genetic diversity regulating the TLR10/TLR1/TLR6 locus confers increased cytokines in response to Chlamydia trachomatis.

Journal Article HGG Adv · January 13, 2022 Human genetic diversity can have profound effects on health outcomes upon exposure to infectious agents. For infections with Chlamydia trachomatis (C. trachomatis), the wide range of genital and ocular disease manifestations are likely influenced by human ... Full text Link to item Cite

Application of a C. trachomatis expression system to identify C. pneumoniae proteins translocated into host cells.

Journal Article J Bacteriol · June 1, 2021 Chlamydia pneumoniae is a Gram-negative, obligate intracellular pathogen that causes community-acquired respiratory infections. C. pneumoniae uses a cell contact-dependent type-III secretion (T3S) system to translocate pathogen effector proteins that manip ... Full text Link to item Cite

Mechanism of 2'-fucosyllactose degradation by human-associated Akkermansia.

Journal Article J Bacteriol · February 22, 2024 Among the first microorganisms to colonize the human gut of breastfed infants are bacteria capable of fermenting human milk oligosaccharides (HMOs). One of the most abundant HMOs, 2'-fucosyllactose (2'-FL), may specifically drive bacterial colonization of ... Full text Link to item Cite

The acetylase activity of Cdu1 regulates bacterial exit from infected cells by protecting Chlamydia effectors from degradation

Journal Article eLife · February 15, 2024 Many cellular processes are regulated by ubiquitin-mediated proteasomal degradation. Pathogens can regulate eukaryotic proteolysis through the delivery of proteins with de-ubiquitinating (DUB) activities. The obligate intracellular pathogen Full text Cite

Use of gene sequences as type for naming prokaryotes: Recommendations of the international committee on the taxonomy of chlamydiae

Journal Article New Microbes and New Infections · September 1, 2023 The International Committee on Systematics of Prokaryotes (ICSP) discussed and rejected in 2020 a proposal to modify the International Code of Nomenclature of Prokaryotes to allow the use of gene sequences as type for naming prokaryotes. An alternative nom ... Full text Cite

Spontaneous episodic inflammation in the intestines of mice lacking HNF4A is driven by microbiota and associated with early life microbiota alterations.

Journal Article mBio · August 31, 2023 The inflammatory bowel diseases (IBD) occur in genetically susceptible individuals who mount inappropriate immune responses to their microbiota leading to chronic intestinal inflammation. Whereas IBD clinical presentation is well described, how interaction ... Full text Link to item Cite

The Chlamydia effector CpoS modulates the inclusion microenvironment and restricts the interferon response by acting on Rab35.

Journal Article mBio · August 31, 2023 The obligate intracellular bacterium Chlamydia trachomatis inserts a family of inclusion membrane (Inc) proteins into the membrane of its vacuole (the inclusion). The Inc CpoS is a critical suppressor of host cellular immune surveillance, but the underlyin ... Full text Link to item Cite

The emerging complexity of Chlamydia trachomatis interactions with host cells as revealed by molecular genetic approaches.

Journal Article Curr Opin Microbiol · August 2023 Chlamydia trachomatis (Ct) is an intracellular bacterial pathogen that relies on the activity of secreted proteins known as effectors to promote replication and avoidance of immune clearance. Understanding the contribution of Ct effectors to pathogenesis h ... Full text Link to item Cite

A genetic system for Akkermansia muciniphila reveals a role for mucin foraging in gut colonization and host sterol biosynthesis gene expression.

Journal Article Nat Microbiol · August 2023 Akkermansia muciniphila, a mucophilic member of the gut microbiota, protects its host against metabolic disorders. Because it is genetically intractable, the mechanisms underlying mucin metabolism, gut colonization and its impact on host physiology are not ... Full text Link to item Cite

The bacterial effector GarD shields Chlamydia trachomatis inclusions from RNF213-mediated ubiquitylation and destruction.

Journal Article Cell Host Microbe · December 14, 2022 Chlamydia trachomatis is the leading cause of sexually transmitted bacterial infections and a major threat to women's reproductive health in particular. This obligate intracellular pathogen resides and replicates within a cellular compartment termed an inc ... Full text Link to item Cite

Chlamydia repurposes the actin-binding protein EPS8 to disassemble epithelial tight junctions and promote infection.

Journal Article Cell host & microbe · December 2022 Invasive microbial pathogens often disrupt epithelial barriers, yet the mechanisms used to dismantle tight junctions are poorly understood. Here, we show that the obligate pathogen Chlamydia trachomatis uses the effector protein TepP to transiently disasse ... Full text Cite

Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment.

Journal Article Sci Transl Med · November 16, 2022 Not all patients with cancer and severe neutropenia develop fever, and the fecal microbiome may play a role. In a single-center study of patients undergoing hematopoietic cell transplant (n = 119), the fecal microbiome was characterized at onset of severe ... Full text Link to item Cite

Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease.

Journal Article Cell · September 29, 2022 The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal ... Full text Link to item Cite

Human genetic diversity regulating the TLR10/TLR1/TLR6 locus confers increased cytokines in response to Chlamydia trachomatis.

Journal Article HGG Adv · January 13, 2022 Human genetic diversity can have profound effects on health outcomes upon exposure to infectious agents. For infections with Chlamydia trachomatis (C. trachomatis), the wide range of genital and ocular disease manifestations are likely influenced by human ... Full text Link to item Cite

Application of a C. trachomatis expression system to identify C. pneumoniae proteins translocated into host cells.

Journal Article J Bacteriol · June 1, 2021 Chlamydia pneumoniae is a Gram-negative, obligate intracellular pathogen that causes community-acquired respiratory infections. C. pneumoniae uses a cell contact-dependent type-III secretion (T3S) system to translocate pathogen effector proteins that manip ... Full text Link to item Cite

Genotypic and Phenotypic Diversity among Human Isolates of Akkermansia muciniphila.

Journal Article mBio · May 18, 2021 The mucophilic anaerobic bacterium Akkermansia muciniphila is a prominent member of the gastrointestinal (GI) microbiota and the only known species of the Verrucomicrobia phylum in the mammalian gut. A high prevalence of A. muciniphila in adult humans is a ... Full text Link to item Cite

An endometrial organoid model of interactions between Chlamydia and epithelial and immune cells.

Journal Article J Cell Sci · March 8, 2021 Our understanding of how the obligate intracellular bacterial pathogen Chlamydia trachomatis reprograms the function of infected cells in the upper genital tract is largely based on observations made in cell culture with transformed epithelial cell lines. ... Full text Link to item Cite

The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights.

Journal Article Obesity (Silver Spring) · March 2021 OBJECTIVE: The purpose of this study was to establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification. METHODS: A total of 223 adolescents aged 10 to 18 years with BMI ≥9 ... Full text Open Access Link to item Cite

Modeling of variables in cellular infection reveals CXCL10 levels are regulated by human genetic variation and the Chlamydia-encoded CPAF protease.

Journal Article Sci Rep · October 26, 2020 Susceptibility to infectious diseases is determined by a complex interaction between host and pathogen. For infections with the obligate intracellular bacterium Chlamydia trachomatis, variation in immune activation and disease presentation are regulated by ... Full text Open Access Link to item Cite

Bacterial genetics and molecular pathogenesis in the age of high throughput DNA sequencing.

Journal Article Curr Opin Microbiol · April 2020 When Stanley Falkow introduced Molecular Koch's Postulates (Falkow, 1988) as a conceptual framework to identify microbial factors that contributed to disease, he reaffirmed the prominent role that the basic principles of genetic analysis should play in def ... Full text Link to item Cite

Insights into the Autoproteolytic Processing and Catalytic Mechanism of the Chlamydia trachomatis Virulence-Associated Protease CPAF.

Journal Article Biochemistry · August 20, 2019 CPAF (chlamydial protease-like activity factor) is a Chlamydia trachomatis protease that is translocated into the host cytosol during infection. CPAF activity results in dampened host inflammation signaling, cytoskeletal remodeling, and suppressed neutroph ... Full text Link to item Cite

Chlamydia trachomatis fails to protect its growth niche against pro-apoptotic insults.

Journal Article Cell Death Differ · August 2019 Chlamydia trachomatis is an obligate intracellular bacterial agent responsible for ocular infections and sexually transmitted diseases. It has been postulated that Chlamydia inhibits apoptosis in host cells to maintain an intact replicative niche until suf ... Full text Link to item Cite

Ptr/CTL0175 Is Required for the Efficient Recovery of Chlamydia trachomatis From Stress Induced by Gamma-Interferon.

Journal Article Front Microbiol · 2019 Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in humans and a frequent cause of asymptomatic, persistent infections leading to serious complications, particularly in young women. Chlamydia displays a unique obligate intra ... Full text Link to item Cite

A renewed tool kit to explore Chlamydia pathogenesis: from molecular genetics to new infection models.

Journal Article F1000Res · 2019 Chlamydia trachomatis is the most prevalent sexually transmitted bacterial pathogen and the leading cause of preventable blindness in the developing world. C. trachomatis invades the epithelium of the conjunctiva and genital tract and replicates within an ... Full text Link to item Cite

Insertional mutagenesis in the zoonotic pathogen Chlamydia caviae.

Journal Article PLoS One · 2019 The ability to introduce targeted genetic modifications in microbial genomes has revolutionized our ability to study the role and mode of action of individual bacterial virulence factors. Although the fastidious lifestyle of obligate intracellular bacteria ... Full text Link to item Cite

The Expanding Molecular Genetics Tool Kit in Chlamydia.

Journal Article J Bacteriol · December 15, 2018 Chlamydia has emerged as an important model system for the study of host pathogen interactions, in part due to a resurgence in the development of tools for its molecular genetic manipulation. An additional tool, published by Keb et al. (G. Keb, R. Hayman, ... Full text Link to item Cite

A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation.

Journal Article Nat Microbiol · December 2018 Pathogenic bacteria are armed with potent effector proteins that subvert host signalling processes during infection1. The activities of bacterial effectors and their associated roles within the host cell are often poorly understood, particularly for Chlamy ... Full text Link to item Cite

An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease.

Journal Article Cell Host Microbe · August 8, 2018 Pathogens have been a strong driving force for natural selection. Therefore, understanding how human genetic differences impact infection-related cellular traits can mechanistically link genetic variation to disease susceptibility. Here we report the Hi-HO ... Full text Open Access Link to item Cite

Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton.

Journal Article Elife · March 7, 2018 Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction. Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyop ... Full text Open Access Link to item Cite

Chlamydia Persistence: A Survival Strategy to Evade Antimicrobial Effects in-vitro and in-vivo.

Journal Article Front Microbiol · 2018 The Chlamydiaceae comprise a group of highly adapted bacterial pathogens sharing a unique intracellular lifestyle. Three Chlamydia species are pathogenic to humans: Chlamydia trachomatis, Chlamydia pneumoniae, and Chlamydia psittaci. C. trachomatis is the ... Full text Link to item Cite

Bacterial Subversion of COG-Dependent Membrane Traffic.

Journal Article Trends Cell Biol · December 2017 Intracellular bacterial pathogens thrive within eukaryotic cells by interacting with a range of organelles to establish a replicative niche. In a new study in Cell Host and Microbe, Miller et al. identify a Brucella abortus effector that subverts membrane ... Full text Link to item Cite

N-Acylated Derivatives of Sulfamethoxazole Block Chlamydia Fatty Acid Synthesis and Interact with FabF.

Journal Article Antimicrob Agents Chemother · October 2017 The type II fatty acid synthesis (FASII) pathway is essential for bacterial lipid biosynthesis and continues to be a promising target for novel antibacterial compounds. Recently, it has been demonstrated that Chlamydia is capable of FASII and this pathway ... Full text Link to item Cite

Assessing the satisfaction and burden within an academic animal care and use program.

Journal Article FASEB J · September 2017 Although animal research requires adherence to various regulations and standards, the manner in which compliance is maintained and the degree of additional constraints varies between institutions. Regulatory burden, particularly if institutionally imposed, ... Full text Link to item Cite

Engineering of obligate intracellular bacteria: progress, challenges and paradigms.

Journal Article Nat Rev Microbiol · September 2017 It is estimated that approximately one billion people are at risk of infection with obligate intracellular bacteria, but little is known about the underlying mechanisms that govern their life cycles. The difficulty in studying Chlamydia spp., Coxiella spp. ... Full text Open Access Link to item Cite

Chlamydia trachomatis' struggle to keep its host alive.

Journal Article Microb Cell · March 2, 2017 Bacteria of the phylum Chlamydiae infect a diverse range of eukaryotic host species, including vertebrate animals, invertebrates, and even protozoa. Characteristics shared by all Chlamydiae include their obligate intracellular lifestyle and a biphasic deve ... Full text Link to item Cite

The Chlamydia trachomatis Inclusion Membrane Protein CpoS Counteracts STING-Mediated Cellular Surveillance and Suicide Programs.

Journal Article Cell Host Microbe · January 11, 2017 Evading cell death is critical for Chlamydia to maintain a replicative niche, but the underlying mechanisms are unknown. We screened a library of Chlamydia mutants for modulators of cell death. Inactivation of the inclusion membrane protein CpoS (Chlamydia ... Full text Link to item Cite

The Effector TepP Mediates Recruitment and Activation of Phosphoinositide 3-Kinase on Early Chlamydia trachomatis Vacuoles.

Journal Article mSphere · 2017 Chlamydia trachomatis delivers multiple type 3 secreted effector proteins to host epithelial cells to manipulate cytoskeletal functions, membrane dynamics, and signaling pathways. TepP is the most abundant effector protein secreted early in infection, but ... Full text Open Access Link to item Cite

Genomic sequencing-based mutational enrichment analysis identifies motility genes in a genetically intractable gut microbe.

Journal Article Proc Natl Acad Sci U S A · December 6, 2016 A major roadblock to understanding how microbes in the gastrointestinal tract colonize and influence the physiology of their hosts is our inability to genetically manipulate new bacterial species and experimentally assess the function of their genes. We de ... Full text Link to item Cite

Molecular Genetic Analysis of Chlamydia Species.

Journal Article Annu Rev Microbiol · September 8, 2016 Species of Chlamydia are the etiologic agent of endemic blinding trachoma, the leading cause of bacterial sexually transmitted diseases, significant respiratory pathogens, and a zoonotic threat. Their dependence on an intracellular growth niche and their p ... Full text Link to item Cite

The Chlamydia-Secreted Protease CPAF Promotes Chlamydial Survival in the Mouse Lower Genital Tract.

Journal Article Infect Immun · September 2016 Despite the extensive in vitro characterization of CPAF (chlamydial protease/proteasome-like activity factor), its role in chlamydial infection and pathogenesis remains unclear. We now report that a Chlamydia trachomatis strain deficient in expression of C ... Full text Link to item Cite

Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant Intracellular Pathogen.

Journal Article Microbiol Mol Biol Rev · June 2016 Chlamydia species infect millions of individuals worldwide and are important etiological agents of sexually transmitted disease, infertility, and blinding trachoma. Historically, the genetic intractability of this intracellular pathogen has hindered the mo ... Full text Link to item Cite

Discovery of the Elusive UDP-Diacylglucosamine Hydrolase in the Lipid A Biosynthetic Pathway in Chlamydia trachomatis.

Journal Article mBio · March 22, 2016 Constitutive biosynthesis of lipid A via the Raetz pathway is essential for the viability and fitness of Gram-negative bacteria, includingChlamydia trachomatis Although nearly all of the enzymes in the lipid A biosynthetic pathway are highly conserved acro ... Full text Open Access Link to item Cite

The Chlamydia trachomatis Protease CPAF Contains a Cryptic PDZ-Like Domain with Similarity to Human Cell Polarity and Tight Junction PDZ-Containing Proteins.

Journal Article PLoS One · 2016 The need for more effective anti-chlamydial therapeutics has sparked research efforts geared toward further understanding chlamydial pathogenesis mechanisms. Recent studies have implicated the secreted chlamydial serine protease, chlamydial protease-like a ... Full text Link to item Cite

A Chlamydia trachomatis strain with a chemically generated amino acid substitution (P370L) in the cthtrA gene shows reduced elementary body production.

Journal Article BMC Microbiol · September 30, 2015 BACKGROUND: Chlamydia (C.) trachomatis is the most prevalent bacterial sexually transmitted infection worldwide and the leading cause of preventable blindness. Genetic approaches to investigate C. trachomatis have been only recently developed due to the or ... Full text Link to item Cite

Global Mapping of the Inc-Human Interactome Reveals that Retromer Restricts Chlamydia Infection.

Journal Article Cell Host Microbe · July 8, 2015 Chlamydia trachomatis is a leading cause of genital and ocular infections for which no vaccine exists. Upon entry into host cells, C. trachomatis resides within a membrane-bound compartment—the inclusion—and secretes inclusion membrane proteins (Incs) that ... Full text Link to item Cite

Integrating chemical mutagenesis and whole-genome sequencing as a platform for forward and reverse genetic analysis of Chlamydia.

Journal Article Cell Host Microbe · May 13, 2015 Gene inactivation by transposon insertion or allelic exchange is a powerful approach to probe gene function. Unfortunately, many microbes, including Chlamydia, are not amenable to routine molecular genetic manipulations. Here we describe an arrayed library ... Full text Link to item Cite

Coxiella burnetii effector proteins that localize to the parasitophorous vacuole membrane promote intracellular replication.

Journal Article Infect Immun · February 2015 The intracellular bacterial pathogen Coxiella burnetii directs biogenesis of a parasitophorous vacuole (PV) that acquires host endolysosomal components. Formation of a PV that supports C. burnetii replication requires a Dot/Icm type 4B secretion system (T4 ... Full text Link to item Cite

Chlamydia trachomatis Infection Leads to Defined Alterations to the Lipid Droplet Proteome in Epithelial Cells.

Journal Article PLoS One · 2015 The obligate intracellular bacterium Chlamydia trachomatis is a major human pathogen and a main cause of genital and ocular diseases. During its intracellular cycle, C. trachomatis replicates inside a membrane-bound vacuole termed an "inclusion". Acquisiti ... Full text Open Access Link to item Cite

Differential Translocation of Host Cellular Materials into the Chlamydia trachomatis Inclusion Lumen during Chemical Fixation.

Journal Article PLoS One · 2015 Chlamydia trachomatis manipulates host cellular pathways to ensure its proliferation and survival. Translocation of host materials into the pathogenic vacuole (termed 'inclusion') may facilitate nutrient acquisition and various organelles have been observe ... Full text Open Access Link to item Cite

A 2-pyridone-amide inhibitor targets the glucose metabolism pathway of Chlamydia trachomatis.

Journal Article mBio · December 30, 2014 UNLABELLED: In a screen for compounds that inhibit infectivity of the obligate intracellular pathogen Chlamydia trachomatis, we identified the 2-pyridone amide KSK120. A fluorescent KSK120 analogue was synthesized and observed to be associated with the C.  ... Full text Link to item Cite

Raphael Valdivia: how Chlamydia settles in.

Journal Article J Cell Biol · October 13, 2014 Valdivia studies how the pathogen Chlamydia trachomatis interacts with its host cell. ... Full text Link to item Cite

Reassessing the role of the secreted protease CPAF in Chlamydia trachomatis infection through genetic approaches.

Journal Article Pathog Dis · August 2014 The secreted Chlamydia protease CPAF cleaves a defined set of mammalian and Chlamydia proteins in vitro. As a result, this protease has been proposed to modulate a range of bacterial and host cellular functions. However, it has recently come into question ... Full text Link to item Cite

Cell biology at the host-microbe interface.

Journal Article Mol Biol Cell · March 2014 Full text Link to item Cite

The Chlamydia trachomatis type III secretion chaperone Slc1 engages multiple early effectors, including TepP, a tyrosine-phosphorylated protein required for the recruitment of CrkI-II to nascent inclusions and innate immune signaling.

Journal Article PLoS Pathog · February 2014 Chlamydia trachomatis, the causative agent of trachoma and sexually transmitted infections, employs a type III secretion (T3S) system to deliver effector proteins into host epithelial cells to establish a replicative vacuole. Aside from the phosphoprotein ... Full text Link to item Cite

Search for microRNAs expressed by intracellular bacterial pathogens in infected mammalian cells.

Journal Article PLoS One · 2014 MicroRNAs are expressed by all multicellular organisms and play a critical role as post-transcriptional regulators of gene expression. Moreover, different microRNA species are known to influence the progression of a range of different diseases, including c ... Full text Open Access Link to item Cite

A chemical mutagenesis approach to identify virulence determinants in the obligate intracellular pathogen Chlamydia trachomatis.

Journal Article Methods Mol Biol · 2014 Our understanding of how most microbes "work" is hindered by the lack of molecular genetic and recombinant DNA tools to manipulate their genomes. We devised an approach to perform genetic analysis in one such microbe, the obligate intracellular bacterial p ... Full text Link to item Cite

Forward genetic approaches in Chlamydia trachomatis.

Journal Article J Vis Exp · October 23, 2013 Chlamydia trachomatis, the etiological agent of sexually transmitted diseases and ocular infections, remains poorly characterized due to its intractability to experimental transformation with recombinant DNA. We developed an approach to perform genetic ana ... Full text Link to item Cite

Mutations in hemG mediate resistance to salicylidene acylhydrazides, demonstrating a novel link between protoporphyrinogen oxidase (HemG) and Chlamydia trachomatis infectivity.

Journal Article J Bacteriol · September 2013 Salicylidene acylhydrazides (SAHs) inhibit the type III secretion system (T3S) of Yersinia and other Gram-negative bacteria. In addition, SAHs restrict the growth and development of Chlamydia species. However, since the inhibition of Chlamydia growth by SA ... Full text Link to item Cite

Chlamydial intracellular survival strategies.

Journal Article Cold Spring Harb Perspect Med · May 1, 2013 Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen and the causative agent of blinding trachoma. Although Chlamydia is protected from humoral immune responses by residing within remodeled intracellular vacuoles, it still must ... Full text Link to item Cite

STING-dependent recognition of cyclic di-AMP mediates type I interferon responses during Chlamydia trachomatis infection.

Journal Article mBio · April 30, 2013 UNLABELLED: STING (stimulator of interferon [IFN] genes) initiates type I IFN responses in mammalian cells through the detection of microbial nucleic acids. The membrane-bound obligate intracellular bacterium Chlamydia trachomatis induces a STING-dependent ... Full text Link to item Cite

IRG and GBP host resistance factors target aberrant, "non-self" vacuoles characterized by the missing of "self" IRGM proteins.

Journal Article PLoS Pathog · 2013 Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune ... Full text Link to item Cite

A new dawn for chlamydia research: These important and challenging pathogens are finally yielding to modern analytic techniques

Journal Article Microbe · September 1, 2012 The chlamydiae are members of a diverse group of bacteria that replicate exclusively within eukaryotic cells. These pathogens cause various illnesses, including preventable blindness and urogenital infections in humans, spontaneous abortions in livestock, ... Cite

Virulence determinants in the obligate intracellular pathogen Chlamydia trachomatis revealed by forward genetic approaches.

Journal Article Proc Natl Acad Sci U S A · January 24, 2012 Chlamydia trachomatis, a pathogen responsible for diseases of significant clinical and public health importance, remains poorly characterized because of its intractability to routine molecular genetic manipulation. We have developed a combinatorial approac ... Full text Link to item Cite

Human genome-wide RNAi screen for host factors that modulate intracellular Salmonella growth.

Journal Article PLoS One · 2012 Salmonella enterica is a bacterial pathogen of humans that can proliferate within epithelial cells as well as professional phagocytes of the immune system. While much has been learned about the microbial genes that influence the infectious process through ... Full text Link to item Cite

Emerging roles for lipid droplets in immunity and host-pathogen interactions.

Journal Article Annu Rev Cell Dev Biol · 2012 Lipid droplets (LDs) are neutral lipid storage organelles ubiquitous to eukaryotic cells. It is increasingly recognized that LDs interact extensively with other organelles and that they perform functions beyond passive lipid storage and lipid homeostasis. ... Full text Link to item Cite

A new dawn for chlamydia research

Journal Article Microbe · January 1, 2012 The chlamydiae are members of a diverse group of bacteria that replicate exclusively within eukaryotic cells. These pathogens cause various illnesses, including preventable blindness and urogenital infections in humans, spontaneous abortions in livestock, ... Full text Cite

Quantitative proteomics reveals metabolic and pathogenic properties of Chlamydia trachomatis developmental forms.

Journal Article Mol Microbiol · December 2011 Chlamydia trachomatis is an obligate intracellular pathogen responsible for ocular and genital infections of significant public health importance. C. trachomatis undergoes a biphasic developmental cycle alternating between two distinct forms: the infectiou ... Full text Link to item Cite

Chlamydia protease-like activity factor (CPAF): characterization of proteolysis activity in vitro and development of a nanomolar affinity CPAF zymogen-derived inhibitor.

Journal Article Biochemistry · September 6, 2011 During infection of epithelial cells, the obligate intracellular pathogen Chlamydia trachomatis secretes the serine protease Chlamydia protease-like activity factor (CPAF) into the host cytosol to regulate a range of host cellular processes through targete ... Full text Link to item Cite

Chlamydial protease-like activity factor (CPAF) enzymatic activity, specificity, and inhibitor design

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 28, 2011 Link to item Cite

The Chlamydia protease CPAF regulates host and bacterial proteins to maintain pathogen vacuole integrity and promote virulence.

Journal Article Cell Host Microbe · July 21, 2011 The obligate intracellular bacterial pathogen Chlamydia trachomatis injects numerous effector proteins into the epithelial cell cytoplasm to manipulate host functions important for bacterial survival. In addition, the bacterium secretes a serine protease, ... Full text Link to item Cite

Lipooligosaccharide is required for the generation of infectious elementary bodies in Chlamydia trachomatis.

Journal Article Proc Natl Acad Sci U S A · June 21, 2011 Lipopolysaccharides (LPS) and lipooligosaccharides (LOS) are the main lipid components of bacterial outer membranes and are essential for cell viability in most Gram-negative bacteria. Here we show that small molecule inhibitors of LpxC [UDP-3-O-(R-3-hydro ... Full text Link to item Cite

Investigation of chlamydial protease-like activity factor (CPAF) enzymatic activity

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · March 27, 2011 Link to item Cite

Uncivil engineers: Chlamydia, Salmonella and Shigella alter cytoskeleton architecture to invade epithelial cells.

Journal Article Future Microbiol · August 2010 The obligate intracellular bacterial pathogen Chlamydia trachomatis is a major cause of blindness and sexually transmitted diseases. Like the enteric pathogens Salmonella and Shigella, Chlamydia injects effector proteins into epithelial cells to initiate e ... Full text Link to item Cite

cPLA2 regulates the expression of type I interferons and intracellular immunity to Chlamydia trachomatis.

Journal Article J Biol Chem · July 9, 2010 Infection with the obligate bacterial intracellular pathogen Chlamydia trachomatis leads to the sustained activation of the small GTPase RAS and many of its downstream signaling components. In particular, the mitogen-activated protein kinase ERK and the ca ... Full text Link to item Cite

Acquisition of nutrients by Chlamydiae: unique challenges of living in an intracellular compartment.

Journal Article Curr Opin Microbiol · February 2010 The Chlamydiae are obligate intracellular pathogens that replicate within a membrane-bound vacuole, termed the 'inclusion'. From this compartment, bacteria acquire essential nutrients by selectively redirecting transport vesicles and hijacking intracellula ... Full text Link to item Cite

New insights into Chlamydia intracellular survival mechanisms.

Journal Article Cell Microbiol · November 2009 Chlamydia sp. are responsible for a wide range of diseases of significant clinical and public health importance. In this review, we highlight how recent cellular and functional genomic approaches have significantly increased our knowledge of the pathogenic ... Full text Link to item Cite

The Chlamydia type III secretion system C-ring engages a chaperone-effector protein complex.

Journal Article PLoS Pathog · September 2009 In Gram-negative bacterial pathogens, specialized chaperones bind to secreted effector proteins and maintain them in a partially unfolded form competent for translocation by type III secretion systems/injectisomes. How diverse sets of effector-chaperone co ... Full text Link to item Cite

Leading a sheltered life: intracellular pathogens and maintenance of vacuolar compartments.

Journal Article Cell Host Microbe · June 18, 2009 Many intracellular pathogens survive in vacuolar niches composed of host-derived membranes modified extensively by pathogen proteins and lipids. Although intracellular lifestyles offer protection from humoral immune responses, vacuole-bound pathogens never ... Full text Link to item Cite

Host-microbe interactions: bacteria.

Journal Article Curr Opin Microbiol · February 2009 Full text Link to item Cite

Pmp-like proteins Pls1 and Pls2 are secreted into the lumen of the Chlamydia trachomatis inclusion.

Journal Article Infect Immun · September 2008 The obligate intracellular pathogen Chlamydia trachomatis secretes effector proteins across the membrane of the pathogen-containing vacuole (inclusion) to modulate host cellular functions. In an immunological screen for secreted chlamydial proteins, we ide ... Full text Link to item Cite

Actin and intermediate filaments stabilize the Chlamydia trachomatis vacuole by forming dynamic structural scaffolds.

Journal Article Cell Host Microbe · August 14, 2008 The obligate intracellular bacterial pathogen Chlamydia trachomatis replicates within a large vacuole or "inclusion" that expands as bacteria multiply but is maintained as an intact organelle. Here, we report that the inclusion is encased in a scaffold of ... Full text Link to item Cite

Cytoplasmic lipid droplets are translocated into the lumen of the Chlamydia trachomatis parasitophorous vacuole.

Journal Article Proc Natl Acad Sci U S A · July 8, 2008 The acquisition of host-derived lipids is essential for the pathogenesis of the obligate intracellular bacteria Chlamydia trachomatis. Current models of chlamydial lipid acquisition center on the fusion of Golgi-derived exocytic vesicles and endosomal mult ... Full text Link to item Cite

Chlamydia effector proteins and new insights into chlamydial cellular microbiology.

Journal Article Curr Opin Microbiol · February 2008 Chlamydia and Chlamydophila sp. are highly related obligate intracellular bacterial pathogens that cause sexually transmitted diseases, ocular infections and atypical pneumonias. Relatively little is known about the molecular mechanisms by which Chlamydiae ... Full text Link to item Cite

Reorganization of the host cytoskeleton by the intracellular pathogen Chlamydia trachomatis.

Journal Article Commun Integr Biol · 2008 Chlamydiae are obligate intracellular pathogens that cause a wide range of human diseases. Chlamydia resides in a membrane bound vacuole ("inclusion") that expands to accommodate replicating bacteria. We recently reported that Chlamydia remodels and recrui ... Full text Link to item Cite

Endosymbiosis: the evil within.

Journal Article Curr Biol · June 5, 2007 A recent study has revealed a novel feature of the symbiosis between a bacterium and a fungal pathogen. In addition to producing a pathogenic toxin, the endosymbiont of the rice pathogen Rhizopus microsporus controls the ability of the fungus to form spora ... Full text Link to item Cite

Identification of host-induced pathogen genes by differential fluorescence induction reporter systems.

Journal Article Nat Protoc · 2007 The ability to monitor a pathogen's gene expression program in response to the host environment is central to understanding host-microbe interactions. This protocol describes the application of a fluorescence-based promoter trap strategy, termed differenti ... Full text Link to item Cite

The obligate intracellular pathogen Chlamydia trachomatis targets host lipid droplets.

Journal Article Curr Biol · August 22, 2006 Lipid droplets (LDs) are ubiquitous but poorly understood neutral-lipid-rich eukaryotic organelles that may participate in functions as diverse as lipid homeostasis, membrane traffic, and signaling . We report that infection with the obligate intracellular ... Full text Link to item Cite

Multifunctional analysis of Chlamydia-specific genes in a yeast expression system.

Journal Article Mol Microbiol · April 2006 Our understanding of how obligate intracellular pathogens co-opt eukaryotic cellular functions has been limited by their intractability to genetic manipulation and by the abundance of pathogen-specific genes with no known functional homologues. In this rep ... Full text Link to item Cite

The uses of green fluorescent protein in prokaryotes.

Journal Article Methods Biochem Anal · 2006 Link to item Cite

The yeasts Rho1p and Pkc1p regulate the transport of chitin synthase III (Chs3p) from internal stores to the plasma membrane.

Journal Article Proc Natl Acad Sci U S A · September 2, 2003 During cell stress, Saccharomyces cerevisiae increases the synthesis of chitin and glucans to strengthen and repair the cell wall. In this study, we show that under conditions of cell stress, the steady-state localization of chitin synthase III (Chs3p) shi ... Full text Link to item Cite

The CD14 receptor does not mediate entry of Mycobacterium tuberculosis into human mononuclear phagocytes.

Journal Article FEMS Immunol Med Microbiol · May 15, 2003 Prior reports have suggested that CD14 mediates uptake of Mycobacterium tuberculosis into porcine alveolar macrophages and human fetal microglia, but the contribution of CD14 to cell entry in human macrophages has not been studied. To address this question ... Full text Link to item Cite

The yeast clathrin adaptor protein complex 1 is required for the efficient retention of a subset of late Golgi membrane proteins.

Journal Article Dev Cell · March 2002 In yeast, certain resident trans-Golgi network (TGN) proteins achieve steady-state localization by cycling through late endosomes. Here, we show that chitin synthase III (Chs3p), an enzyme involved in the assembly of the cell wall at the mother-bud junctio ... Full text Link to item Cite

mig-14 is a horizontally acquired, host-induced gene required for salmonella enterica lethal infection in the murine model of typhoid fever.

Journal Article Infect Immun · December 2000 We have characterized a host-induced virulence gene, mig-14, that is required for fatal infection in the mouse model of enteric fever. mig-14 is present in all Salmonella enterica subspecies I serovars and maps to a region of the chromosome that appears to ... Full text Link to item Cite

Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes.

Journal Article Nature · October 21, 1999 Specialized epithelia known as M cells overlying the lymphoid follicles of Peyer's patches are important in the mucosal immune system, but also provide a portal of entry for pathogens such as Salmonella typhimurium, Mycobacterium bovis, Shigella flexneri, ... Full text Link to item Cite

Regulatory network analysis.

Journal Article Trends Microbiol · October 1999 Full text Link to item Cite

1.1 Detection of Virulence Genes Expressed within Infected Cells

Journal Article Methods in Microbiology · December 1, 1998 Full text Cite

Macrophage-dependent induction of the Salmonella pathogenicity island 2 type III secretion system and its role in intracellular survival.

Journal Article Mol Microbiol · October 1998 Salmonella pathogenicity island 2 (SPI-2) encodes a putative type III secretion system necessary for systemic infection in animals. We have investigated the transcriptional organization and regulation of SPI-2 by creating gfp fusions throughout the entire ... Full text Link to item Cite

Flow cytometry and bacterial pathogenesis.

Journal Article Curr Opin Microbiol · June 1998 Our understanding of microbial adaptations to diverse and threatening environments is limited by the assumption that the behavior of individual bacteria can be accurately determined by measuring the behavior of populations. Recent advances in gene expressi ... Full text Link to item Cite

Fluorescence-based isolation of bacterial genes expressed within host cells.

Journal Article Science · September 26, 1997 A selection strategy was devised to identify bacterial genes preferentially expressed when a bacterium associates with its host cell. Fourteen Salmonella typhimurium genes, which were under the control of at least four independent regulatory circuits, were ... Full text Link to item Cite

Probing bacterial gene expression within host cells.

Journal Article Trends Microbiol · September 1997 The study of bacterial gene expression in the host environment is critical to our understanding of the disease process. New research tools, such as luciferase and green fluorescent protein, provide the means to measure bacterial responses to the intracellu ... Full text Link to item Cite

Mycobacterium marinum causes both long-term subclinical infection and acute disease in the leopard frog (Rana pipiens).

Journal Article Infect Immun · February 1997 Mycobacterium marinum grows at an optimal temperature of 33 degrees C, far lower than that for M. tuberculosis. Consequently, M. marinum infection of mammals is restricted largely to the cooler surfaces of the body, such as the extremities, but it causes a ... Full text Link to item Cite

Enhanced green fluorescent protein vectors that provide stronger fluorescence intensities and higher expression in mammalian cells

Journal Article FASEB Journal · December 1, 1996 The green fluorescent protein (GFP) from the jellyfish Aequorea victoria has become an important reporter molecule for monitoring gene expression and protein localization in vivo and in real time. Unlike other bioluminescent reporters, the chromophore in G ... Cite

Bacterial genetics by flow cytometry: rapid isolation of Salmonella typhimurium acid-inducible promoters by differential fluorescence induction.

Journal Article Mol Microbiol · October 1996 The ability of Salmonella typhimurium to survive and replicate within murine macrophages is dependent on a low phagosomal pH. This requirement for an acidic vacuole suggests that low pH is an important environmental stimulus for the transcription of genes ... Full text Link to item Cite

FACS-optimized mutants of the green fluorescent protein (GFP).

Journal Article Gene · 1996 We have constructed a library in Escherichia coli of mutant gfp genes (encoding green fluorescent protein, GFP) expressed from a tightly regulated inducible promoter. We introduced random amino acid (aa) substitutions in the twenty aa flanking the chromoph ... Full text Link to item Cite

Applications for green fluorescent protein (GFP) in the study of host-pathogen interactions.

Journal Article Gene · 1996 The green fluorescent protein (GFP) from Aequorea victoria is a novel fluorescent marker that has potential use in the study of bacterial pathogenicity. To explore some of the potential applications of GFP to the study of host-parasite interactions, we con ... Full text Link to item Cite

Characterization of a putative periplasmic transport system for octopine accumulation encoded by Agrobacterium tumefaciens Ti plasmid pTiA6.

Journal Article J Bacteriol · October 1991 Neoplastic crown gall tumors incited by Agrobacterium tumefaciens release novel amino acid or sugar derivatives known as opines, whose synthesis is directed by genes transferred to plant cells. Agrobacterium cells can transport and catabolize these compoun ... Full text Link to item Cite