4.4 Article

Novel Role for the yceGH Tellurite Resistance Genes in the Pathogenesis of Bacillus anthracis

Journal

INFECTION AND IMMUNITY
Volume 82, Issue 3, Pages 1132-1140

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.01614-13

Keywords

-

Funding

  1. NIH [AI065993]
  2. NIGMS [GM068524]
  3. Hartwell Foundation
  4. Texas Christian University Research and Creative Activities Fund [60670]

Ask authors/readers for more resources

Bacillus anthracis, the causative agent of anthrax, relies on multiple virulence factors to subvert the host immune defense. Using Caenorhabditis elegans as an infection model, we screened approximately 5,000 transposon mutants of B. anthracis Sterne for decreased virulence. One of the attenuated mutants resulted in loss of expression of yceG and yceH, the last two genes in a six-gene cluster of tellurite resistance genes. We generated an analogous insertional mutant to confirm the phenotype and characterize the role of yceGH in resistance to host defenses. Loss of yceGH rendered the mutants more sensitive to tellurite toxicity as well as to host defenses such as reactive oxygen species and the cathelicidin family of antimicrobial peptides. Additionally, we see decreased survival in mammalian models of infection, including human whole blood and in mice. We identify a novel role for the yceGH genes in B. anthracis Sterne virulence and suggest that C. elegans is a useful infection model to study anthrax pathogenesis.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.4
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Microbiology

Loss of the ClpXP Protease Leads to Decreased Resistance to Cell-Envelope Targeting Antimicrobials in Bacillus anthracis Sterne

Lang Zou, Christopher R. Evans, Vuong D. Do, Quinn P. Losefsky, Diem Q. Ngo, Shauna M. McGillivray

Summary: The ClpX ATPase is crucial for Bacillus anthracis resistance to cell envelope targeting antibiotics by forming ClpXP protease. Disruption of clpP genes increases susceptibility to antimicrobials, but neither gene is essential for virulence. Changes in cell envelope morphology, including increased hydrophobicity and cell division defects, were observed in Delta clpX strain.

FRONTIERS IN MICROBIOLOGY (2021)

Article Biology

Environmental conditions dictate differential evolution of vancomycin resistance in Staphylococcus aureus

Henrique Machado, Yara Seif, George Sakoulas, Connor A. Olson, Ying Hefner, Amitesh Anand, Ying Z. Jones, Richard Szubin, Bernhard O. Palsson, Victor Nizet, Adam M. Feist

Summary: Henrique Machado and colleagues describe mutational mechanisms associated with MRSA vancomycin resistance in Staphylococcus aureus using adaptive laboratory evolution experiments focused on tolerance. Their results reveal environment-dependent mutational strategies to vancomycin tolerization and the impact of mutations in regulatory genes, providing insight into the development of antibiotic resistance under multiple conditions.

COMMUNICATIONS BIOLOGY (2021)

Article Microbiology

Impact of Clopidogrel on Clinical Outcomes in Patients with Staphylococcus aureus Bacteremia: a National Retrospective Cohort Study

Aisling R. Caffrey, Haley J. Appaneal, Kerry L. LaPlante, Vrishali V. Lopes, Erlinda R. Ulloa, Victor Nizet, George Sakoulas

Summary: This study demonstrates that the use of P2Y12 inhibitor clopidogrel can reduce in-hospital mortality in patients with Staphylococcus aureus bacteremia.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2022)

Article Microbiology

Increased Innate Immune Susceptibility in Hyperpigmented Bacteriophage-Resistant Mutants of Pseudomonas aeruginosa

Nitasha D. Menon, Samuel Penziner, Elizabeth T. Montano, Raymond Zurich, David T. Pride, Bipin G. Nair, Geetha B. Kumar, Victor Nizet

Summary: Bacteriophage therapy is an alternative treatment to antibiotics for multidrug-resistant pathogens. This study found that phage therapy can lead to the emergence of phage-resistant mutants with pyomelanin pigmentation, but these mutants are less virulent due to large genomic deletions and retain susceptibility to the antibiotic colistin. This suggests that they do not pose a contraindication to using anti-pseudomonal phage therapy.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2022)

Article Immunology

Contribution of Streptococcus pyogenes M87 protein to innate immune resistance and virulence

Yujiro Hirose, Piotr Kolesinski, Masanobu Hiraoka, Satoshi Uchiyama, Raymond H. Zurich, Monika Kumaraswamy, Elisabet Bjanes, Partho Ghosh, Shigetada Kawabata, Victor Nizet

Summary: This study shows that the M87 protein of Streptococcus pyogenes strain emm87 acts as a virulence factor by modulating the interaction between the bacteria and innate immune cells, contributing to bacterial resistance and the release of mature IL-1 beta.

MICROBIAL PATHOGENESIS (2022)

Article Biology

An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37

Piotr Kolesinski, Kuei-Chen Wang, Yujiro Hirose, Victor Nizet, Partho Ghosh

Summary: This study revealed the specific binding mechanism between the Streptococcus pyogenes M protein and the human antimicrobial peptide LL-37, providing important insights into the drug resistance of streptococcus.

ELIFE (2022)

Review Pharmacology & Pharmacy

Transfer of antibiotics and their metabolites in human milk: Implications for infant health and microbiota

Sydney P. Thomas, Erce Denizer, Simone Zuffa, Brookie M. Best, Lars Bode, Christina D. Chambers, Pieter C. Dorrestein, George Y. Liu, Jeremiah D. Momper, Victor Nizet, Shirley M. Tsunoda, Adriana H. Tremoulet

Summary: Antibiotics are crucial for perinatal care, but they can harm the host gut microbiota. Current studies mainly focus on the effects of antibiotics on infants directly or through maternal use, with limited knowledge about the risks of antibiotics in human milk to infants.

PHARMACOTHERAPY (2023)

Article Materials Science, Multidisciplinary

Influence of Surface Properties and Microbial Growth Media on Antibacterial Action of ZnO

Dustin Johnson, John M. Reeks, Alexander Caron, Iakovos Tzoka, Iman Ali, Shauna M. McGillivray, Yuri M. Strzhemechny

Summary: Nano- and microscale ZnO exhibit robust antibacterial action, and microscale particles show similar antibacterial efficacy to nano-powders. The structural and optoelectronic changes in ZnO depend on the media type and the presence (or absence) of bacteria. Further evidence supports significant cytotoxicity without particle internalization, highlighting the importance of surface and media interactions in this process.

COATINGS (2022)

Article Microbiology

Man vs Microbes-The Race of the Century

Ericka Anderson, Bipin Nair, Victor Nizet, Geetha Kumar

Summary: The complexity of antimicrobial resistance (AMR) crisis and its global impact on healthcare requires understanding of the underlying forces and implementation of innovative solutions. Future therapeutic interventions should focus on host-pathogen interactions to enhance the innate immune system and reduce pathogen virulence. Interrupting pathogen survival strategies and using clonotyping assays to identify 'super clones' can guide targeted antibiotic regimens. Innovative alternatives to traditional antibiotics, such as bacteriophage therapy and repurposing drugs, are being successfully used to combat AMR. Policy changes, including shorter durations of antibiotic treatment and increased surveillance measures, can enhance patient safety and global prevention and control programs.

JOURNAL OF MEDICAL MICROBIOLOGY (2023)

Article Immunology

Enhancer-instructed epigenetic landscape and chromatin compartmentalization dictate a primary antibody repertoire protective against specific bacterial pathogens

E. Mauricio Barajas-Mora, Lindsay Lee, Hanbin Lu, J. Andres Valderrama, Elisabet Bjanes, Victor Nizet, Ann J. J. Feeney, Ming Hu, Cornelis Murre

Summary: Researchers have identified a specific enhancer, E34, within the Igk locus, which is crucial for chromatin remodeling and repositioning, and promotes the rearrangement of Igkv7-33 V-kappa-J(kappa) genes necessary for the production of anti-phosphorylcholine-specific antibodies. Mice lacking E34 are more susceptible to Streptococcus pneumoniae infections.

NATURE IMMUNOLOGY (2023)

Article Engineering, Biomedical

Outer Membrane Vesicle-Coated Nanoparticle Vaccine Protects against Acinetobacter baumannii Pneumonia and Sepsis

Elisabet Bjanes, Jiarong Zhou, Tariq Qayum, Nishta Krishnan, Raymond H. Zurich, Nitasha D. Menon, Alexandria Hoffman, Ronnie H. Fang, Liangfang Zhang, Victor Nizet

Summary: This study reports a vaccine platform that combines gold nanoparticles coated with immunogenic Acinetobacter baumannii outer membrane vesicles (Ab-OMVs). It induces high levels of IgG antibodies in rabbits, enhances neutrophil killing of A. baumannii, and provides passive protection against sepsis in mice. Active immunization with the Ab-NP vaccine in mice protects against sepsis and pneumonia, activates B cells and dendritic cells, improves neutrophil responses, and mitigates cytokine storm.

ADVANCED NANOBIOMED RESEARCH (2023)

Article Infectious Diseases

Nafcillin Augmentation of Daptomycin and Cathelicidin LL-37 Killing of Methicillin-resistant Staphylococcus epidermidis: Foundations of Successful Therapy of Endocarditis

Lucy Catteau, Yvan Diaz Iglesias, Hannah Tsunemoto, Joseph Pogliano, Francoise Van Bambeke, Victor Nizet, George Sakoulas

Summary: Methicillin-resistant Staphylococcus epidermidis (MRSE) endocarditis, which does not respond to conventional therapy, can be effectively treated with the combination of nafcillin and daptomycin. In vitro studies have shown that nafcillin enhances the killing of MRSE by daptomycin, both in planktonic cells and biofilms. Nafcillin also sensitizes MRSE to killing by human neutrophils and cathelicidin antimicrobial peptide LL-37. Clinical studies are needed to determine the optimal timing for the use of these regimens to improve clinical outcomes.

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS (2023)

Article Multidisciplinary Sciences

A pharmacoproteomic landscape of organotypic intervention responses in Gram-negative sepsis

Tirthankar Mohanty, Christofer A. Q. Karlsson, Yashuan Chao, Erik Malmstrom, Eleni Bratanis, Andrietta Grentzmann, Martina Morch, Victor Nizet, Lars Malmstrom, Adam Linder, Oonagh Shannon, Johan Malmstrom

Summary: This study used pharmacoproteomics to evaluate the time-dependent treatment effects of meropenem and methylprednisolone on a murine Escherichia coli sepsis model. Three distinct proteome response patterns were identified, which depended on the underlying proteotype for each organ. The findings provide insights for guiding treatment timing, dosage, and potential combination therapies.

NATURE COMMUNICATIONS (2023)

Article Biology

The Parasporal Body of Bacillus thuringiensis subsp. israelensis: A Unique Phage Capsid-Associated Prokaryotic Insecticidal Organelle

Sarah R. Rudd, Leticia Silva Miranda, Hannah R. Curtis, Yves Bigot, Mercedes Diaz-Mendoza, Robert Hice, Victor Nizet, Hyun-Woo Park, Gregor Blaha, Brian A. Federici, Dennis K. Bideshi

Summary: This paper introduces three important commercial bacterial insecticides derived from different subspecies of Bacillus thuringiensis (Bt), including their sources and uses. It also explores the unique features of Bt subspecies israelensis, such as the structure of the parasporal body (PB) and the multilaminar fibrous matrix (MFM), as well as the functions and structural similarities of two proteins, Bt152 and Bt075. Additionally, a novel molecular process for targeting Cry and Cyt proteins has been identified.

BIOLOGY-BASEL (2023)

Article Biophysics

Microscale ZnO with controllable crystal morphology as a platform to study antibacterial action on Staphylococcus aureus

John M. Reeks, Iman Ali, William J. Moss, Eric Davis, Shauna M. McGillivray, Yuri M. Strzhemechny

Summary: Nano- and microcrystalline ZnO is a versatile material with various applications, one of which includes inhibiting bacterial growth. Despite extensive research on its antimicrobial properties, the fundamental mechanisms underlying growth inhibition are still unclear.

BIOINTERPHASES (2021)

No Data Available