Article
Microbiology
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
Immunology
Mingjie Jin, Siyu Liang, Jing Wang, Huihui Zhang, Yueling Zhang, Wanjiang Zhang, Siguo Liu, Fang Xie
Summary: This study reveals the important role of the PepO protease in Streptococcus suis by assisting the bacterium in resisting cathelicidin-mediated killing. PepO cleaves and degrades cathelicidins LL-37 and mCRAMP, impairing their antibacterial abilities and affecting neutrophil migration, anti-apoptosis activity, and lysosome development in macrophages. Furthermore, the loss of PepO attenuates organ injury and bacterial burdens in a murine model of S. suis bacteraemia.
Article
Cell Biology
Debabrata Biswas, Poornima Ambalavanan, Miriam Ravins, Aparna Anand, Abhinay Sharma, Kimberly Xuan Zhen Lim, Rachel Ying Min Tan, Hwee Ying Lim, Asaf Sol, Gilad Bachrach, Veronique Angeli, Emanuel Hanski
Summary: Research has shown that Group A Streptococcus can resist host immune responses by cleaving the host's antimicrobial peptide LL-37, leading to soft-tissue infections. Furthermore, the activation of host receptors mediated by LL-37 is critical for defense against GAS infections.
Article
Multidisciplinary Sciences
Leonardo Cecotto, Kok van Kessel, Margreet A. Wolfert, Charles Vogely, Bart van der Wal, Harrie Weinans, Jos van Strijp, Saber Amin Yavari
Summary: This study investigated the antibacterial and immunomodulatory properties of three cationic host defense peptides (HDPs) in the context of Staphylococcus aureus infections. The results showed that while all three HDPs inhibited the activation of human macrophages, only one of them prevented the growth of S. aureus. Another HDP reduced bacterial uptake by macrophages but did not improve killing efficiency against intracellular S. aureus. The study suggests that combination of different HDPs or synergistic use with other antibacterial agents could enhance immune cells' efficacy against S. aureus pathogenesis.
Review
Medicine, Research & Experimental
Prince N. Dlozi, Angelina Gladchuk, Rustin D. Crutchley, Nicole Keuler, Renier Coetzee, Admire Dube
Summary: Tuberculosis and HIV continue to pose significant global health challenges, highlighting the urgent need for novel therapeutic strategies. Host mediated immune response through antimicrobial peptides shows promise in TB and HIV management, but faces complex challenges in pharmaceutical development. Nanoparticle formulations offer potential solutions for targeted drug delivery and improved efficacy in these therapeutic interventions.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biotechnology & Applied Microbiology
Ezgi Ulkuseven, David J. McCanna, Lakshman N. Subbaraman, Lyndon W. Jones
Summary: Antimicrobial peptides are a class of polypeptides composed of less than 100 amino acids, demonstrating strong activity against infectious bacteria. Among the peptides studied, polymyxin E and nisin showed potential for treating ocular infections with low toxicity to human corneal epithelial cells.
PROBIOTICS AND ANTIMICROBIAL PROTEINS
(2021)
Article
Biology
Pramod K. Jangir, Lois Ogunlana, Petra Szili, Marton Czikkely, Liam P. Shaw, Emily J. Stevens, Yu Yang, Qiue Yang, Yang Wang, Csaba Pal, Timothy R. Walsh, Craig R. MacLean
Summary: Antimicrobial peptides (AMPs) have potential as a solution to antibiotic resistance crisis, but the evolution of resistance to therapeutic AMPs could lead to resistance to host AMPs, compromising the innate immune response. The study found that the globally disseminated mobile colistin resistance (MCR) in Escherichia coli increased resistance to human and animal AMPs and enhanced bacterial growth and virulence. These findings have significant implications for the use of AMPs and suggest that eradicating MCR may be challenging even with the withdrawal of colistin.
Article
Gastroenterology & Hepatology
Theodore Rokkas, David Y. Graham
Summary: Previously, antimicrobial therapy for Helicobacter pylori infections was based on expert opinions and local effectiveness. However, with the recent advancements in potassium competitive acid blockers and availability of susceptibility testing, there are now more opportunities for pharmacological optimization in H. pylori treatment. The ability to obtain H. pylori susceptibility data using stool samples allows for routine susceptibility-based therapy.
EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Rebecca M. Kandell, Julia A. Kudryashev, Ester J. Kwon
Summary: Traumatic brain injury is a critical public health concern, and a fluorescent activity-based nanosensor can help visualize the pathophysiology of the disease. By actively targeting the brain extracellular matrix, the distribution and activation of the nanosensor can be improved.
Review
Infectious Diseases
Zhiqian Lyu, Pan Yang, Jian Lei, Jinbiao Zhao
Summary: The emergence of drug-resistant genes and food safety concerns from antibiotic overuse have highlighted the need for alternative methods to antibiotics. Antimicrobial peptides can effectively replace antibiotics in killing pathogens and enhancing host immune functions. However, there are limitations to their application in livestock production and human medicine.
Article
Immunology
Arshad Rizvi, German Vargas-Cuebas, Adrianne N. Edwards, Michael A. DiCandia, Zavier A. Carter, Cheyenne D. Lee, Marcos P. Monteiro, Shonna M. McBride
Summary: This study reveals the significance of glycine in C. difficile pathogenesis and colonization, with the host peptide signals playing a role in regulating glycine metabolism. These findings contribute to a better understanding of C. difficile infection mechanisms.
INFECTION AND IMMUNITY
(2023)
Article
Rheumatology
Mahadevappa Hemshekhar, Dylan Lloyd, Hani El-Gabalawy, Neeloffer Mookherjee
Summary: This study demonstrates that oral administration of a bioavailable curcumin formulation can reduce the levels of cathelicidin and calprotectin in joints, and regulate both local and systemic inflammation in inflammatory arthritis.
ARTHRITIS RESEARCH & THERAPY
(2023)
Review
Immunology
Bruno Rivas-Santiago, Yolanda Jacobo-Delgado, Adrian Rodriguez-Carlos
Summary: Host defense peptides, initially named to refer to host immunity peptides, are now seen as a potential solution to combat drug-resistant microorganisms and emerging viruses like coronaviruses, due to their broad antimicrobial capacity and immunomodulatory activity. This review assesses whether these peptides and their derivatives are prepared to be part of the treatment for the next coronavirus pandemic, given the history of coronavirus outbreaks and pandemics in the 21st century.
ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS
(2021)
Article
Pharmacology & Pharmacy
Darren Shu Jeng Ting, Jianguo Li, Chandra S. Verma, Eunice T. L. Goh, Mario Nubile, Leonardo Mastropasqua, Dalia G. Said, Roger W. Beuerman, Rajamani Lakshminarayanan, Imran Mohammed, Harminder S. Dua
Summary: CaD23 is a novel synthetic HDP with strong antimicrobial efficacy, especially in combination with antibiotics. Its rapid antimicrobial action is mainly attributed to its membrane-permeabilising mechanism, and MD simulations are useful for elucidating its mechanism of action and guiding design optimization.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Materials Science, Biomaterials
Wenjing Zhang, Shuai Deng, Min Zhou, Jingcheng Zou, Jiayang Xie, Ximian Xiao, Ling Yuan, Zhemin Ji, Sheng Chen, Ruxin Cui, Zhengjie Luo, Guixue Xia, Runhui Liu
Summary: This study designed amphiphilic peptoid polymers by mimicking the structure of HDPs and synthesized a series of cyclic peptoid polymers. The optimal polymer exhibited strong antibacterial activity and potential application against drug-resistant bacteria.
BIOMATERIALS SCIENCE
(2022)
Article
Microbiology
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
Microbiology
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
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
Biochemistry & Molecular Biology
Pooja Srinivas, Kenneth C. Keiler, Christine M. Dunham
Summary: Bacteria use trans-translation to rescue stalled ribosomes and target incomplete proteins. New structural and biochemical data reveal important differences between trans-translation and traditional translation processes. These differences provide insights into the fundamental nature of trans-translation and guide the development of new antibiotics that specifically target bacteria.
Article
Immunology
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
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.
Review
Pharmacology & Pharmacy
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.
Article
Materials Science, Multidisciplinary
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.
Article
Microbiology
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
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.
Article
Engineering, Biomedical
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
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
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
Microbiology
Neeraja Marathe, Ha An Nguyen, John N. Alumasa, Alexandra B. Kuzmishin Nagy, Michael Vazquez, Christine M. Dunham, Kenneth C. Keiler
Summary: This study reports a small molecule inhibitor called KKL-55 that specifically targets the interaction between EF-Tu and tmRNA, inhibiting bacterial translation without affecting normal translation. This discovery provides a potential avenue for developing new antibiotics to treat drug-resistant infections.
Article
Biology
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.