Sleeper cells: the stringent response and persistence in the Borreliella (Borrelia ) burgdorferi enzootic cycle

Division of the genus Borrelia into two genera (corresponding to Lyme disease and relapsing fever groups) reflects their genetic and phenotypic distinctiveness and will lead to a better understanding of these two groups of microbes (Margos et al. (2016) There is inadequate evidence to support the division of the genus Borrelia. Int. J. Syst. Evol. Microbiol. doi: 10.1099/ijsem.0.001717)

(2017) Alan G. Barbour et al.   INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY

Antibiotic tolerance facilitates the evolution of resistance

(2017) Irit Levin-Reisman et al.   SCIENCE

Tolerant, Growing Cells from Nutrient Shifts Are Not Persister Cells

(2017) Jun-Seob Kim et al.   mBio

Stringent Response Factors PPX1 and PPK2 Play an Important Role in Mycobacterium tuberculosis Metabolism, Biofilm Formation, and Sensitivity to IsoniazidIn Vivo

(2016) Yu-Min Chuang et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Persisters—as elusive as ever

(2016) Niilo Kaldalu et al.   APPLIED MICROBIOLOGY AND BIOTECHNOLOGY

Biology and Applications of CRISPR Systems: Harnessing Nature’s Toolbox for Genome Engineering

(2016) Addison V. Wright et al.   CELL

Interaction of the Lyme disease spirochete with its tick vector

(2016) Melissa J. Caimano et al.   CELLULAR MICROBIOLOGY

Molecular mechanisms and clinical implications of bacterial persistence

(2016) Joran Elie Michiels et al.   DRUG RESISTANCE UPDATES

Regulation of Growth, Cell Shape, Cell Division, and Gene Expression by Second Messengers (p)ppGpp and Cyclic Di-GMP in Mycobacterium smegmatis

(2016) Kuldeepkumar Ramnaresh Gupta et al.   JOURNAL OF BACTERIOLOGY

ppGpp Binding to a Site at the RNAP-DksA Interface Accounts for Its Dramatic Effects on Transcription Initiation during the Stringent Response

(2016) Wilma Ross et al.   MOLECULAR CELL

The magic dance of the alarmones (p)ppGpp

(2016) Wieland Steinchen et al.   MOLECULAR MICROBIOLOGY

Global Tn-seq analysis of carbohydrate utilization and vertebrate infectivity of Borrelia burgdorferi

(2016) Erin B. Troy et al.   MOLECULAR MICROBIOLOGY

Distinguishing between resistance, tolerance and persistence to antibiotic treatment

(2016) Asher Brauner et al.   NATURE REVIEWS MICROBIOLOGY

The physiology of growth arrest: uniting molecular and environmental microbiology

(2016) Megan Bergkessel et al.   NATURE REVIEWS MICROBIOLOGY

In vivoexpression technology and 5′ end mapping of theBorrelia burgdorferitranscriptome identify novel RNAs expressed during mammalian infection

(2016) Philip P. Adams et al.   NUCLEIC ACIDS RESEARCH

ppGpp negatively impacts ribosome assembly affecting growth and antimicrobial tolerance in Gram-positive bacteria

(2016) Rebecca M. Corrigan et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Mechanisms of bacterial persistence during stress and antibiotic exposure

(2016) Alexander Harms et al.   SCIENCE

Two Different Virulence-Related Regulatory Pathways in Borrelia burgdorferi Are Directly Affected by Osmotic Fluxes in the Blood Meal of Feeding Ixodes Ticks

(2016) Sébastien Bontemps-Gallo et al.   PLoS Pathogens

A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library

(2016) Jie Feng et al.   Frontiers in Microbiology

Lyme borreliosis

(2016) Allen C. Steere et al.   Nature Reviews Disease Primers

RNA-Seq of Borrelia burgdorferi in Multiple Phases of Growth Reveals Insights into the Dynamics of Gene Expression, Transcriptome Architecture, and Noncoding RNAs

(2016) William K. Arnold et al.   PLoS One

Impacts of Global Transcriptional Regulators on Persister Metabolism

(2015) Wendy W. K. Mok et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Persister Development by Borrelia burgdorferi PopulationsIn Vitro

(2015) John R. Caskey et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells

(2015) Bijaya Sharma et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Ecology and Epidemiology of Lyme Borreliosis

(2015) Anna M. Schotthoefer et al.   CLINICS IN LABORATORY MEDICINE

Diversity in (p)ppGpp metabolism and effectors

(2015) Kuanqing Liu et al.   CURRENT OPINION IN MICROBIOLOGY

A Short-Term Borrelia burgdorferi Infection Model Identifies Tissue Tropisms and Bloodstream Survival Conferred by Adhesion Proteins

(2015) Jennifer A. Caine et al.   INFECTION AND IMMUNITY

BB0744 Affects Tissue Tropism and Spatial Distribution of Borrelia burgdorferi

(2015) Beau Wager et al.   INFECTION AND IMMUNITY

Apparent Role for Borrelia burgdorferi LuxS during Mammalian Infection

(2015) William K. Arnold et al.   INFECTION AND IMMUNITY

The Stringent Response Regulator DksA Is Required for Salmonella enterica Serovar Typhimurium Growth in Minimal Medium, Motility, Biofilm Formation, and Intestinal Colonization

(2015) Shalhevet Azriel et al.   INFECTION AND IMMUNITY

DksA and (p)ppGpp Have Unique and Overlapping Contributions to Haemophilus ducreyi Pathogenesis in Humans

(2015) Concerta L. Holley et al.   INFECTION AND IMMUNITY

Phenotypic Heterogeneity Enables Uropathogenic Escherichia coli To Evade Killing by Antibiotics and Serum Complement

(2015) Marta Putrinš et al.   INFECTION AND IMMUNITY

Viable but Nonculturable and Persister Cells Coexist Stochastically and Are Induced by Human Serum

(2015) M. Ayrapetyan et al.   INFECTION AND IMMUNITY

Cyclic di-GMP Modulates Gene Expression in Lyme Disease Spirochetes at the Tick-Mammal Interface To Promote Spirochete Survival during the Blood Meal and Tick-to-Mammal Transmission

(2015) Melissa J. Caimano et al.   INFECTION AND IMMUNITY

Diagnosis and Treatment of Lyme Arthritis

(2015) Sheila L. Arvikar et al.   INFECTIOUS DISEASE CLINICS OF NORTH AMERICA

From (p)ppGpp to (pp)pGpp: Characterization of Regulatory Effects of pGpp Synthesized by the Small Alarmone Synthetase of Enterococcus faecalis

(2015) Anthony O. Gaca et al.   JOURNAL OF BACTERIOLOGY

Many Means to a Common End: the Intricacies of (p)ppGpp Metabolism and Its Control of Bacterial Homeostasis

(2015) Anthony O. Gaca et al.   JOURNAL OF BACTERIOLOGY

Regulation of Bacterial Virulence by Csr (Rsm) Systems

(2015) Christopher A. Vakulskas et al.   MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS

Lack of intracellular trehalose affects formation of Escherichia coli persister cells

(2015) Dorota Kuczyńska-Wiśnik et al.   MICROBIOLOGY-SGM

Morphological and biochemical features of Borrelia burgdorferi pleomorphic forms

(2015) Leena Meriläinen et al.   MICROBIOLOGY-SGM

Remarkable Functional Convergence: Alarmone ppGpp Mediates Persistence by Activating Type I and II Toxin-Antitoxins

(2015) Kenn Gerdes et al.   MOLECULAR CELL

Obg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance

(2015) Natalie Verstraeten et al.   MOLECULAR CELL

Regulation of CsrB/C sRNA decay by EIIAGlcof the phosphoenolpyruvate: carbohydrate phosphotransferase system

(2015) Yuanyuan Leng et al.   MOLECULAR MICROBIOLOGY

The BBA33 lipoprotein binds collagen and impactsBorrelia burgdorferipathogenesis

(2015) Hui Zhi et al.   MOLECULAR MICROBIOLOGY

BadR (BB0693) controls growth phase-dependent induction ofrpoSandbosRinBorrelia burgdorferivia recognizing TAAAATAT motifs

(2015) Zhiming Ouyang et al.   MOLECULAR MICROBIOLOGY

Recent functional insights into the role of (p)ppGpp in bacterial physiology

(2015) Vasili Hauryliuk et al.   NATURE REVIEWS MICROBIOLOGY

New insights into the regulatory mechanisms of ppGpp and DksA on Escherichia coli RNA polymerase–promoter complex

(2015) Nicola Doniselli et al.   NUCLEIC ACIDS RESEARCH

Correlation of Culture Positivity, PCR Positivity, and Burden of Borrelia burgdorferi Sensu Lato in Skin Samples of Erythema Migrans Patients with Clinical Findings

(2015) Daša Stupica et al.   PLoS One

Characterization of the RelBbu Regulon in Borrelia burgdorferi Reveals Modulation of Glycerol Metabolism by (p)ppGpp

(2015) Julia V. Bugrysheva et al.   PLoS One

Stochastic induction of persister cells by HipA through (p)ppGpp-mediated activation of mRNA endonucleases

(2015) Elsa Germain et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The Borrelia burgdorferi RelA/SpoT Homolog and Stringent Response Regulate Survival in the Tick Vector and Global Gene Expression during Starvation

(2015) Dan Drecktrah et al.   PLoS Pathogens

Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein

(2015) Devender Kumar et al.   PLoS Pathogens

Persister mechanisms in Borrelia burgdorferi: implications for improved intervention

(2015) Jie Feng et al.   Emerging Microbes & Infections

A phylogenomic and molecular marker based proposal for the division of the genus Borrelia into two genera: the emended genus Borrelia containing only the members of the relapsing fever Borrelia, and the genus Borreliella gen. nov. containing the members of the Lyme disease Borrelia (Borrelia burgdorferi sensu lato complex)

(2014) Mobolaji Adeolu et al.   ANTONIE VAN LEEUWENHOEK INTERNATIONAL JOURNAL OF GENERAL AND MOLECULAR MICROBIOLOGY

Molecular Mechanisms Underlying Bacterial Persisters

(2014) Etienne Maisonneuve et al.   CELL

Gut Microbiota of the Tick Vector Ixodes scapularis Modulate Colonization of the Lyme Disease Spirochete

(2014) Sukanya Narasimhan et al.   Cell Host & Microbe

Xenodiagnosis to Detect Borrelia burgdorferi Infection: A First-in-Human Study

(2014) Adriana Marques et al.   CLINICAL INFECTIOUS DISEASES

Stage-specific global alterations in the transcriptomes of Lyme disease spirochetes during tick feeding and following mammalian host adaptation

(2014) Radha Iyer et al.   MOLECULAR MICROBIOLOGY

Phenotypic bistability in Escherichia coli's central carbon metabolism

(2014) O. Kotte et al.   Molecular Systems Biology

Nutrient Transitions Are a Source of Persisters in Escherichia coli Biofilms

(2014) Stephanie M. Amato et al.   PLoS One

Resurgence of Persisting Non-Cultivable Borrelia burgdorferi following Antibiotic Treatment in Mice

(2014) Emir Hodzic et al.   PLoS One

The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi

(2014) Elizabeth A. Novak et al.   Frontiers in Cellular and Infection Microbiology

That's my story, and I'm sticking to it—an update on B. burgdorferi adhesins

(2014) Catherine A. Brissette et al.   Frontiers in Cellular and Infection Microbiology

The role of metabolism in bacterial persistence

(2014) Stephanie M. Amato et al.   Frontiers in Microbiology

Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library

(2014) Jie Feng et al.   Emerging Microbes & Infections

Persisters, persistent infections and the Yin–Yang model

(2014) Ying Zhang   Emerging Microbes & Infections

RETRACTED: (p)ppGpp Controls Bacterial Persistence by Stochastic Induction of Toxin-Antitoxin Activity

(2013) Etienne Maisonneuve et al.   CELL

Design, synthesis and structure–activity relationship of novel Relacin analogs as inhibitors of Rel proteins

(2013) Ezequiel Wexselblatt et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Study of the Response Regulator Rrp1 Reveals Its Regulatory Role in Chitobiose Utilization and Virulence of Borrelia burgdorferi

(2013) Ching Wooen Sze et al.   INFECTION AND IMMUNITY

Cyclic Di-GMP Receptor PlzA Controls Virulence Gene Expression through RpoS in Borrelia burgdorferi

(2013) Ming He et al.   INFECTION AND IMMUNITY

GTP Dysregulation in Bacillus subtilis Cells Lacking (p)ppGpp Results in Phenotypic Amino Acid Auxotrophy and Failure To Adapt to Nutrient Downshift and Regulate Biosynthesis Genes

(2013) A. Kriel et al.   JOURNAL OF BACTERIOLOGY

Dynamics of connective-tissue localization during chronic Borrelia burgdorferi infection

(2013) Denise M Imai et al.   LABORATORY INVESTIGATION

Molecular Mechanism of Bacterial Persistence by HipA

(2013) Elsa Germain et al.   MOLECULAR CELL

Metabolic Control of Persister Formation in Escherichia coli

(2013) Stephanie M. Amato et al.   MOLECULAR CELL

Borreliahost adaptation Regulator (BadR) regulatesrpoSto modulate host adaptation and virulence factors inBorrelia burgdorferi

(2013) Christine L. Miller et al.   MOLECULAR MICROBIOLOGY

A problem of persistence: still more questions than answers?

(2013) Nathalie Q. Balaban et al.   NATURE REVIEWS MICROBIOLOGY

Differential regulation by ppGpp versus pppGpp in Escherichia coli

(2013) Undine Mechold et al.   NUCLEIC ACIDS RESEARCH

Quantitative Detection of Borrelia burgdorferi sensu lato in Erythema Migrans Skin Lesions Using Internally Controlled Duplex Real Time PCR

(2013) Maria O’Rourke et al.   PLoS One

Illuminating the roles of the Borrelia burgdorferi adhesins

(2013) Jenifer Coburn et al.   TRENDS IN MICROBIOLOGY

Bacterial lifestyle shapes stringent response activation

(2013) Cara C. Boutte et al.   TRENDS IN MICROBIOLOGY

Assessment of Transcriptional Activity of Borrelia burgdorferi and Host Cytokine Genes During Early and Late Infection in a Mouse Model

(2013) Emir Hodzic et al.   VECTOR-BORNE AND ZOONOTIC DISEASES

Comprehensive comparative-genomic analysis of Type 2 toxin-antitoxin systems and related mobile stress response systems in prokaryotes

(2012) Kira S Makarova et al.   Biology Direct

Activation of the RpoN-RpoS regulatory pathway during the enzootic life cycle of Borrelia burgdorferi

(2012) Zhiming Ouyang et al.   BMC MICROBIOLOGY

Post-transcriptional regulation on a global scale: form and function of Csr/Rsm systems

(2012) Tony Romeo et al.   ENVIRONMENTAL MICROBIOLOGY

Borrelia burgdorferi Needs Chemotaxis To Establish Infection in Mammals and To Accomplish Its Enzootic Cycle

(2012) Ching Wooen Sze et al.   INFECTION AND IMMUNITY

Remains of infection

(2012) Alan Barbour   JOURNAL OF CLINICAL INVESTIGATION

Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy

(2012) Linda K. Bockenstedt et al.   JOURNAL OF CLINICAL INVESTIGATION

Detection of Borrelia burgdorferi Nucleic Acids after Antibiotic Treatment Does Not Confirm Viability

(2012) Radha Iyer et al.   JOURNAL OF CLINICAL MICROBIOLOGY

ppGpp: magic beyond RNA polymerase

(2012) Zachary D. Dalebroux et al.   NATURE REVIEWS MICROBIOLOGY

Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection

(2012) Monica E. Embers et al.   PLoS One

Effect of Levels of Acetate on the Mevalonate Pathway of Borrelia burgdorferi

(2012) Tricia A. Van Laar et al.   PLoS One

Binding Mechanism of Metal⋅NTP Substrates and Stringent-Response Alarmones to Bacterial DnaG-Type Primases

(2012) Richard U. Rymer et al.   STRUCTURE

Critical Analysis of Treatment Trials of Rhesus Macaques Infected with Borrelia burgdorferi Reveals Important Flaws in Experimental Design

(2012) Gary P. Wormser et al.   VECTOR-BORNE AND ZOONOTIC DISEASES

Borrelia burgdorferi Requires the Alternative Sigma Factor RpoS for Dissemination within the Vector during Tick-to-Mammal Transmission

(2012) Star M. Dunham-Ems et al.   PLoS Pathogens

Burden and viability of Borrelia burgdorferi in skin and joints of patients with erythema migrans or lyme arthritis

(2011) Xin Li et al.   ARTHRITIS AND RHEUMATISM

Patterns and regulation of ribosomal RNA transcription in Borrelia burgdorferi

(2011) Julia V Bugrysheva et al.   BMC MICROBIOLOGY

Anti-Borrelia burgdorferi Antibody Profile in Post-Lyme Disease Syndrome

(2011) Abhishek Chandra et al.   Clinical and Vaccine Immunology

Oligopeptide Permease A5 Modulates Vertebrate Host-Specific Adaptation of Borrelia burgdorferi

(2011) B. V. Subba Raju et al.   INFECTION AND IMMUNITY

Effects on Growth by Changes of the Balance between GreA, GreB, and DksA Suggest Mutual Competition and Functional Redundancy in Escherichia coli

(2011) D. Vinella et al.   JOURNAL OF BACTERIOLOGY

Carbon storage regulator A (CsrABb) is a repressor of Borrelia burgdorferi flagellin protein FlaB

(2011) Ching Wooen Sze et al.   MOLECULAR MICROBIOLOGY

Circuitry linking the Csr and stringent response global regulatory systems

(2011) Adrianne N. Edwards et al.   MOLECULAR MICROBIOLOGY

Active Starvation Responses Mediate Antibiotic Tolerance in Biofilms and Nutrient-Limited Bacteria

(2011) D. Nguyen et al.   SCIENCE

Borrelia burgdorferi Requires Glycerol for Maximum Fitness During The Tick Phase of the Enzootic Cycle

(2011) Christopher J. Pappas et al.   PLoS Pathogens

Molecular Interactions that Enable Movement of the Lyme Disease Agent from the Tick Gut into the Hemolymph

(2011) Lili Zhang et al.   PLoS Pathogens

Cyclic di-GMP is Essential for the Survival of the Lyme Disease Spirochete in Ticks

(2011) Ming He et al.   PLoS Pathogens

Persister Cells

(2010) Kim Lewis   Annual Review of Microbiology

ppGpp is the major source of growth rate control in E. coli

(2010) Katarzyna Potrykus et al.   ENVIRONMENTAL MICROBIOLOGY

Analysis of a Borrelia burgdorferi phosphodiesterase demonstrates a role for cyclic-di-guanosine monophosphate in motility and virulence

(2010) Syed Z. Sultan et al.   MOLECULAR MICROBIOLOGY

Ineffectiveness of Tigecycline against Persistent Borrelia burgdorferi

(2009) S. W. Barthold et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Chitobiose utilization in Borrelia burgdorferi is dually regulated by RpoD and RpoS

(2009) Ryan G Rhodes et al.   BMC MICROBIOLOGY

Antibiotic Treatment of Animals Infected with Borrelia burgdorferi

(2009) G. P. Wormser et al.   CLINICAL MICROBIOLOGY REVIEWS

Identification and molecular characterization of a cyclic-di-GMP effector protein, PlzA (BB0733): additional evidence for the existence of a functional cyclic-di-GMP regulatory network in the Lyme disease spirochete,Borrelia burgdorferi

(2009) John C. Freedman et al.   FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY

Characterization of a Conditional bosR Mutant in Borrelia burgdorferi

(2009) J. A. Hyde et al.   INFECTION AND IMMUNITY

Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks

(2009) Star M. Dunham-Ems et al.   JOURNAL OF CLINICAL INVESTIGATION

Rrp1, a cyclic-di-GMP-producing response regulator, is an important regulator ofBorrelia burgdorfericore cellular functions

(2009) Elizabeth A. Rogers et al.   MOLECULAR MICROBIOLOGY

The Role of relA and spoT in Yersinia pestis KIM5+ Pathogenicity

(2009) Wei Sun et al.   PLoS One

Characterization of Borrelia burgdorferi Aggregates

(2009) Siddharth Y. Srivastava et al.   VECTOR-BORNE AND ZOONOTIC DISEASES

Small Molecule Control of Virulence Gene Expression in Francisella tularensis

(2009) James C. Charity et al.   PLoS Pathogens

(p)ppGpp: Still Magical?

(2008) Katarzyna Potrykus et al.   Annual Review of Microbiology

Persistence of Borrelia burgdorferi following Antibiotic Treatment in Mice

(2008) E. Hodzic et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Essential Role of the Response Regulator Rrp2 in the Infectious Cycle of Borrelia burgdorferi

(2008) B. K. Boardman et al.   INFECTION AND IMMUNITY

Transcriptional interplay among the regulators Rrp2, RpoN and RpoS in Borrelia burgdorferi

(2008) Z. Ouyang et al.   MICROBIOLOGY-SGM

The global, ppGpp-mediated stringent response to amino acid starvation in Escherichia coli

(2008) Matthew F. Traxler et al.   MOLECULAR MICROBIOLOGY

Epistasis — the essential role of gene interactions in the structure and evolution of genetic systems

(2008) Patrick C. Phillips   NATURE REVIEWS GENETICS

The Stringent Response and Cell Cycle Arrest in Escherichia coli

(2008) Daniel J. Ferullo et al.   PLoS Genetics