Scholars@Duke
Robert J Bastidas

Robert J Bastidas

Assistant Research Professor in Integrative Immunobiology
Integrative Immunobiology
robert.bastidas@duke.edu
4200 MSRB III, Box 3580, Durham, NC 27710
4200 MSRB III Box 3580, 3 Genome Court, Durham, NC 27710

Selected Publications

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

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

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

Forward and Reverse Genetic Analysis of Chlamydia.

Chapter · 2019 Chlamydia is a major etiological agent of human disease that affects millions of individuals worldwide. Historically, our understanding of the mechanisms that contribute to its pathogenesis has been limited. However, the recent development of powerful gene ... 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

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

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

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

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

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

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

Antifungal drug resistance evoked via RNAi-dependent epimutations.

Journal Article Nature · September 25, 2014 Microorganisms evolve via a range of mechanisms that may include or involve sexual/parasexual reproduction, mutators, aneuploidy, Hsp90 and even prions. Mechanisms that may seem detrimental can be repurposed to generate diversity. Here we show that the hum ... 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

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

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

Rapamycin exerts antifungal activity in vitro and in vivo against Mucor circinelloides via FKBP12-dependent inhibition of Tor.

Journal Article Eukaryot Cell · March 2012 The zygomycete Mucor circinelloides is an opportunistic fungal pathogen that commonly infects patients with malignancies, diabetes mellitus, and solid organ transplants. Despite the widespread use of antifungal therapy in the management of zygomycosis, the ... Full text Link to item Cite

Conservation, duplication, and loss of the Tor signaling pathway in the fungal kingdom.

Journal Article BMC Genomics · September 23, 2010 BACKGROUND: The nutrient-sensing Tor pathway governs cell growth and is conserved in nearly all eukaryotic organisms from unicellular yeasts to multicellular organisms, including humans. Tor is the target of the immunosuppressive drug rapamycin, which in c ... Full text Open Access Link to item Cite

TORC1 signaling in the budding yeast endomembrane system and control of cell-cell adhesion in pathogenic fungi

Journal Article · January 1, 2010 The rapamycin-sensitive TORC1 protein kinase is the central component of a conserved signal transduction cascade controlling cell growth in response to nutrients and growth factors. Groundbreaking studies are uncovering novel roles for the endomembrane ves ... Full text Cite

The protein kinase Tor1 regulates adhesin gene expression in Candida albicans.

Journal Article PLoS Pathog · February 2009 Eukaryotic cell growth is coordinated in response to nutrient availability, growth factors, and environmental stimuli, enabling cell-cell interactions that promote survival. The rapamycin-sensitive Tor1 protein kinase, which is conserved from yeasts to hum ... Full text Link to item Cite

Trimorphic stepping stones pave the way to fungal virulence.

Journal Article Proc Natl Acad Sci U S A · January 13, 2009 Full text Link to item Cite

Signaling cascades as drug targets in model and pathogenic fungi.

Journal Article Curr Opin Investig Drugs · August 2008 Microbes evolved to produce natural products that inhibit growth of competing soil microorganisms. In many cases these compounds act on fungi, which are eukaryotes with conserved gene sequences closely related to metazoans, including humans. The calcineuri ... Link to item Cite

Nutritional control via Tor signaling in Saccharomyces cerevisiae.

Journal Article Curr Opin Microbiol · April 2008 The yeast Saccharomyces cerevisiae senses and responds to nutrients by adapting its growth rate and undergoing morphogenic transitions to ensure survival. The Tor pathway is a major integrator of nutrient-derived signals that in coordination with other sig ... Full text Link to item Cite

The virulence of human pathogenic fungi: notes from the South of France.

Journal Article Cell Host Microbe · August 16, 2007 The Second FEBS Advanced Lecture Course on Human Fungal Pathogens: Molecular Mechanisms of Host-Pathogen Interactions and Virulence, organized by Christophe d'Enfert (Institut Pasteur, France), Anita Sil (UCSF, USA), and Steffen Rupp (Fraunhofer, IGB, Germ ... Full text Link to item Cite

A conserved family of enzymes that phosphorylate inositol hexakisphosphate.

Journal Article Science · April 6, 2007 Inositol pyrophosphates are a diverse group of high-energy signaling molecules whose cellular roles remain an active area of study. We report a previously uncharacterized class of inositol pyrophosphate synthase and find it is identical to yeast Vip1 and A ... Full text Link to item Cite

Generation of phytate-free seeds in Arabidopsis through disruption of inositol polyphosphate kinases.

Journal Article Proc Natl Acad Sci U S A · August 30, 2005 Phytate (inositol hexakisphosphate, IP6) is a regulator of intracellular signaling, a highly abundant animal antinutrient, and a phosphate store in plant seeds. Here, we report a requirement for inositol polyphosphate kinases, AtIPK1 and AtIPK2beta, for th ... Full text Link to item Cite

Molecular definition of a novel inositol polyphosphate metabolic pathway initiated by inositol 1,4,5-trisphosphate 3-kinase activity in Saccharomyces cerevisiae.

Journal Article J Biol Chem · July 29, 2005 The production of inositol polyphosphate (IPs) and pyrophosphates (PP-IPs) from inositol 1,4,5-trisphosphate (I(1,4,5)P3) requires the 6-/3-/5-kinase activity of Ipk2 (also known as Arg82 and inositol polyphosphate multikinase). Here, we probed the distinc ... Full text Link to item Cite