Article
Immunology
Exene E. Anderson, Sophie Dyzenhaus, Juliana K. Ilmain, Mitchell J. Sullivan, Harm van Bakel, Victor J. Torres
Summary: Staphylococcus aureus is a successful pathogen capable of suppressing the immune system through the production of various virulence factors. A transcription factor called SarS has been discovered to act as a potent repressor of the leukocidins LukED and LukSF-PV, enhancing the pathogen's virulence. Additionally, naturally occurring mutations in the sarS promoter have been found to increase sarS expression and further repress leukocidins in clinical isolates of S. aureus. This study expands our understanding of the regulation of virulence factors by S. aureus.
INFECTION AND IMMUNITY
(2023)
Article
Immunology
Eshraq Tantawy, Nicoletta Schwermann, Tjorven Ostermeier, Annette Garbe, Heike Baehre, Marius Vital, Volker Winstel
Summary: The study revealed that Adenosine synthase A (AdsA) from Staphylococcus aureus can generate both dAdo and dGuo, two cytotoxic deoxyribonucleosides that increase macrophage cell death. This discovery sheds light on the pathogen's strategy to maximize survival within hosts and may contribute to the development of new therapeutic interventions against multidrug-resistant staphylococci.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Kristin Jahn, Stefan Handtke, Raghavendra Palankar, Thomas P. Kohler, Jan Wesche, Martina Wolff, Janina Bayer, Christiane Wolz, Andreas Greinacher, Sven Hammerschmidt
Summary: This study investigated the effects of Staphylococcus aureus and Streptococcus pneumoniae toxins on human platelets. The results showed that alpha-hemolysin of S. aureus had a significant impact on platelet activation and thrombus formation, while other toxins had little effect. These findings may have clinical relevance for the treatment of S. aureus-induced endocarditis.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Immunology
Nhu T. Q. Nguyen, Thien N. M. Doan, Kei Sato, Christine Tkaczyk, Bret R. Sellman, Binh An Diep
Summary: This study established a rabbit model of Staphylococcus aureus septic shock and demonstrated the potential of immunotherapy in preventing or halting the disease progression.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Andreas F. Haag, Lassi Liljeroos, Paolo Donato, Clarissa Pozzi, Tarcisio Brignoli, Matthew J. Bottomley, Fabio Bagnoli, Isabel Delany
Summary: Vaccination and phage therapy are potential strategies to prevent or combat Staphylococcus aureus infections. In this study, a high-throughput qRT-PCR assay was used to identify highly expressed staphylococcal genes, lukE and lukD, which encode detoxified recombinant proteins. Immunization with these proteins conferred protection against staphylococcal skin infection in mice. This approach of studying in vivo gene expression can guide the selection and design of effective vaccine antigens.
MICROBIOLOGY SPECTRUM
(2023)
Article
Infectious Diseases
Junshu Yang, Christopher Brown, Wayland Noland, Timothy J. Johnson, Yinduo Ji
Summary: The slow discovery of new antibiotics and the rapid development of bacterial resistance have put us in a vulnerable position. We are running out of effective treatment options for antibiotic-resistant infections. However, a study has identified a promising molecule called MZ-01, which exhibits potent bactericidal activity against multidrug-resistant Gram-positive bacterial pathogens, including MRSA. MZ-01 also has low cytotoxicity, making it a potential scaffold for the development of novel antibacterial agents.
Article
Biochemistry & Molecular Biology
Wan Yang, Vijay Singh Gondil, Dehua Luo, Jin He, Hongping Wei, Hang Yang
Summary: The study involves incorporating silica-binding peptide and anti-staphylococcal lysin into functional coatings to kill Staphylococcus aureus and prevent biofilm formation. SiBP1-ClyF-functionalized coatings effectively kill MRSA strains and support normal growth of mammalian cells on surfaces.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Infectious Diseases
Mikaeel Young, Danica J. Walsh, Elysia Masters, Vijay Singh Gondil, Emily Laskey, Michael Klaczko, Hani Awad, James McGrath, Edward M. Schwarz, Christian Melander, Paul M. Dunman
Summary: Methicillin-resistant Staphylococcus aureus (MRSA) is a global healthcare concern. Recent studies have shown that penicillin binding protein 4 (PBP4) is also involved in MRSA resistance. Inhibitors targeting PBP4 may reverse methicillin resistance and inhibit MRSA's ability to cause chronic osteomyelitis.
Article
Biochemistry & Molecular Biology
Amy J. Rice, Russell P. Pesavento, Jinhong Ren, Isoo Youn, Youngjin Kwon, Kassapa Ellepola, Chun-Tao Che, Michael E. Johnson, Hyun Lee
Summary: The study identified small molecule inhibitors of S. aureus DHOase through high-throughput screening and direct binding analysis, laying the foundation for further design of antimicrobial inhibitors against S. aureus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Erick Adrian Cruz-Lopez, Gildardo Rivera, Maria Antonia Cruz-Hernandez, Ana Veronica Martinez-Vazquez, Graciela Castro-Escarpulli, Rebeca Flores-Magallon, Karina Vazquez, Wendy Lizeth Cruz-Pulido, Virgilio Bocanegra-Garcia
Summary: The CRISPR-Cas system provides defense mechanisms against mobile genetic elements in bacteria and archaea, but its role in Staphylococcus aureus is not fully understood. Analysis of over 700 genomes revealed that only a small percentage of S. aureus strains harbor the CRISPR-Cas system, with some spacer sequences matching plasmids and bacteriophages. Further research on a larger number of strains is needed to fully understand the implications of the CRISPR/Cas system in S. aureus.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Immunology
Rosanna Leuzzi, Margherita Bodini, Isaac P. Thomsen, Elisabetta Soldaini, Erika Bartolini, Alessandro Muzzi, Bruna Clemente, Bruno Galletti, Andrea Guido Oreste Manetti, Cinzia Giovani, Stefano Censini, Sonia Budroni, Fabiana Spensieri, Erica Borgogni, Silvia Rossi Paccani, Immaculada Margarit, Fabio Bagnoli, Giuseppe Del Giudice, Clarence B. Creech
Summary: The study identified specific cytokine and functional antibody signatures in patients with different primary invasive diseases caused by Staphylococcus aureus. These data provide insights into human responses to invasive staphylococcal infections and are important for guiding the identification of novel preventive and therapeutic interventions against S. aureus. Our findings showed distinct differences in inflammatory responses and antibody levels between patients with invasive S. aureus disease and healthy donors.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Li Tan, Yi Yang, Weilong Shang, Zhen Hu, Huagang Peng, Shu Li, Xiaomei Hu, Xiancai Rao
Summary: The study identified lysine succinylation (Ksucc) and acetylation (Kac) sites in vancomycin-intermediate Staphylococcus aureus (VISA) and revealed their enrichment in critical metabolic pathways. The cross talk between Ksucc and Kac modifications was observed, and a bifunctional enzyme, SaCobB, with both deacetylation and desuccinylation activities was identified. These findings provide valuable insights into the regulatory mechanisms of PTMs in Staphylococcus aureus.
MICROBIOLOGY SPECTRUM
(2022)
Article
Cell Biology
Zhimin Bai, Min Chen, Qiaofa Lin, Ying Ye, Hongmei Fan, Kaizhen Wen, Jianxing Zeng, Donghong Huang, Wenfei Mo, Ying Lei, Zhijun Liao
Summary: By extracting feature vectors from protein sequences and using classification tools, MRSA and MSSA were successfully distinguished. MRSA showed high resistance to penicillin and high pathogenic risk. Cross-infection between different types of MRSA was found in Quanzhou, and MRSA in traditional hospitals exhibited increasingly blurred molecular characteristics.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Nathanial J. Torres, Devon N. Rizzo, Maria A. Reinberg, Mary-Elizabeth Jobson, Brendan C. Totzke, Jessica K. Jackson, Wenqi Yu, Lindsey N. Shaw
Summary: We have identified two M20B aminopeptidases that play an integral role in the pathogenesis of S. aureus. The deletion of leucine aminopeptidase has been previously shown to attenuate the virulence of S. aureus. In this study, we investigated the role of 10 other aminopeptidases and found that mutations in PepT1 and PepT2 from the M20B family significantly decreased survival and impaired the ability to resist phagocytosis and survive within human macrophages.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Minhye Shin, Daye Mun, Hye Jin Choi, Sooah Kim, Shelley M. Payne, Younghoon Kim
Summary: Staphylococcus aureus RF122 Feo system is a major pathogen causing bovine mastitis, and the new antimicrobial agent PHT-427 efficiently inhibits this system, attenuating various virulence factors related to milk quality, enhancing bacterial antibiotic susceptibility, and showing no toxicity on animal model systems.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Immunology
Jeffrey Fernandez, Holly Sanders, Jessica Henn, Jolaine M. Wilson, Danielle Malone, Alessandra Buoninfante, Matthew Willms, Rita Chan, Ashley L. DuMont, Craig McLahan, Kaitlyn Grubb, Anthony Romanello, Germie van den Dobbelsteen, Victor J. Torres, Jan T. Poolman
Summary: Vaccines against Staphylococcus aureus have been elusive for over three decades, but the leukocidin AB has shown potential as a vaccine antigen. Using a minipig deep surgical wound infection model, the efficacy of LukAB toxoid as a vaccine candidate was demonstrated.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Microbiology
Keenan A. Lacey, Sandra Gonzalez, Frank Yeung, Gregory Putzel, Magdalena Podkowik, Alejandro Pironti, Bo Shopsin, Ken Cadwell, Victor J. Torres
Summary: Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of hospital-acquired pneumonia. Researchers have found that treating mice with broad-spectrum antibiotics makes them more susceptible to low-virulence antibiotic-resistant pathogens. This increased susceptibility is not due to changes in the microbiome, but rather to dehydration and caloric restriction caused by the antibiotic treatment. This model provides a convenient way to study the pathogenesis of hospital-acquired pathogens.
Article
Immunology
Juan Gago, Thomas D. Filardo, Sarah Conderino, Samuel J. Magaziner, Yanina Dubrovskaya, Kenneth Inglima, Eduardo Iturrate, Alejandro Pironti, Jonas Schluter, Ken Cadwell, Sarah Hochman, Huilin Li, Victor J. Torres, Lorna E. Thorpe, Bo Shopsin
Summary: The study found that NBSIs primarily occurred in severely ill COVID-19 patients and were associated with higher mortality. Early recognition of risk factors among COVID-19 patients could potentially decrease NBSI-associated mortality through early treatment.
OPEN FORUM INFECTIOUS DISEASES
(2022)
Editorial Material
Microbiology
Ivan C. Acosta, Francis Alonzo Iii
Summary: Tissue damage and persistent inflammation are distinct features of antibiotic-resistant chronic infections. In this study, Tang et al. demonstrate that anti-folate antibiotics can trigger the synthesis of a bacterial second messenger, leading to an excessive immune response and establishing a paradigm for chronic infection.
CELL HOST & MICROBE
(2022)
Article
Multidisciplinary Sciences
Erin E. Zwack, Ze Chen, Joseph C. Devlin, Zhi Li, Xuhui Zheng, Ada Weinstock, Keenan A. Lacey, Edward A. Fisher, David Fenyo, Kelly V. Ruggles, P'ng Loke, Victor J. Torres
Summary: Infection with Staphylococcus aureus weakens the transcriptional response and downregulates genes related to innate immune response and cytokine signaling, leading to impaired neutrophil recruitment. This transcriptional suppression is conserved across different S. aureus clones and is absent in blood exposed to heat-killed S. aureus or infected with less virulent Staphylococcus epidermidis. The master regulator S. aureus exoprotein expression and its regulated pore-forming toxins are key mediators of this transcriptional suppression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Lucie Bernard-Raichon, Mericien Venzon, Jon Klein, Jordan E. Axelrad, Chenzhen Zhang, Alexis P. Sullivan, Grant A. Hussey, Arnau Casanovas-Massana, Maria G. Noval, Ana M. Valero-Jimenez, Juan Gago, Gregory Putzel, Alejandro Pironti, Evan Wilder, Lorna E. Thorpe, Dan R. Littman, Meike Dittmann, Kenneth A. Stapleford, Bo Shopsin, Victor J. Torres, Albert Ko, Akiko Iwasaki, Ken Cadwell, Jonas Schluter
Summary: The authors demonstrate that SARS-CoV-2 infection causes dysbiosis in the gut microbiome and alterations in gut epithelial cells in a mouse model. They also correlate the observed dysbiosis in COVID-19 patients with bloodstream infections by matching bacterial sequences from stool samples to organisms found in the blood. This study provides evidence that dysbiosis in the gut microbiome is associated with translocation of bacteria into the blood during COVID-19, leading to life-threatening secondary infections.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Gal Avital, Felicia Kuperwaser, Andrew W. Pountain, Keenan A. Lacey, Erin E. Zwack, Magdalena Podkowik, Bo Shopsin, Victor J. Torres, Itai Yanai
Summary: This study investigates the dynamics of macrophage inflammation in response to various bacterial pathogens. Transcriptomic analysis reveals different cellular states within responding macrophages, and modulating the duration of infection and the presence of toxins impacts the trajectory of inflammation.
Article
Biochemistry & Molecular Biology
Krystal L. Ching, Maren de Vries, Juan Gago, Kristen Dancel-Manning, Joseph Sall, William J. Rice, Clea Barnett, Feng-Xia Liang, Lorna E. Thorpe, Bo Shopsin, Leopoldo N. Segal, Meike Dittmann, Victor J. Torres, Ken Cadwell, Alireza Khodadadi-Jamayran, Aristotelis Tsirigos
Summary: Extracellular vesicles called exosomes have been found to play a crucial role in intercellular communication and tissue homeostasis. Recent studies have shown that a subset of exosomes, called defensosomes, are mobilized during bacterial infection and may also contribute to the antiviral response against SARS-CoV-2, the virus responsible for COVID-19.
Editorial Material
Cell Biology
Krystal L. Ching, Victor J. Torres, Ken Cadwell
Summary: In recent years, the contribution of exosomes to immunity, inflammation and host-pathogen interaction have been appreciated. It has been found that exosomes decorated with ACE2, the SARS-CoV-2 cellular receptor, are produced in the lungs of patients with COVID-19, and their increased concentration is associated with decreased hospitalization length.
Article
Immunology
Zachary J. J. Resko, Caleb M. M. Anderson, Michael J. J. Federle, Francis Alonzo III
Summary: The peptidoglycan of Staphylococcus aureus plays an important role in subverting host immune defenses and protecting against stressors. The glucosaminidase SagB processes peptidoglycan chains, which is crucial for IL-1 beta production. SagB-mediated IL-1 beta production is independent of traditional receptor engagement and caspase activity, suggesting a novel mechanism for IL-1 beta maturation.
INFECTION AND IMMUNITY
(2023)
Article
Cell Biology
Shushan Sargsian, Ze Chen, Soo Ching Lee, Amicha Robertson, Rafaela Saes Thur, Julia Sproch, Joseph C. Devlin, Mian Zi Tee, Yi Xian Er, Richard Copin, Adriana Heguy, Alejandro Pironti, Victor J. Torres, Kelly V. Ruggles, Yvonne A. L. Lim, Jeffrey Bethony, P'ng Loke, Ken Cadwell
Summary: Helminth colonization is associated with gut microbiota composition, and Peptostreptococcaceae isolated from the Orang Asli population in Malaysia display superior capacity to promote the life cycle of whipworm species.
Article
Cell Biology
Christophe Langouet-Astrie, Kaori Oshima, Sarah A. McMurtry, Yimu Yang, Jakub M. Kwiecinski, Wells B. LaRiviere, Jeffrey S. Kavanaugh, Igor Zakharevich, Kirk C. Hansen, Deling Shi, Fuming Zhang, Kristina M. Boguslawski, Sofya S. Perelman, Gouwei Su, Victor J. Torres, Jian Liu, Alexander R. Horswill, Eric P. Schmidt
Summary: This study found that influenza infection dynamically induces methicillin-resistant Staphylococcus aureus (MRSA) to increase cytotoxin expression while decreasing metabolic pathways. The activity of a specific cytotoxin is shaped by the post-influenza lung microenvironment, as it is activated by epithelial glycocalyx fragments released after influenza infection. The severity of post-influenza MRSA pneumonia is influenced by bidirectional host-pathogen interactions.
Article
Microbiology
Peter T. Buckley, Rita Chan, Jeffrey Fernandez, Jinquan Luo, Keenan A. Lacey, Ashley L. DuMont, Aidan O'Malley, Randall J. Brezski, Songmao Zheng, Thomas Malia, Brian Whitaker, Adam Zwolak, Angela Payne, Desmond Clark, Martin Sigg, Eilyn R. Lacy, Anna Kornilova, Debra Kwok, Steve McCarthy, Bingyuan Wu, Brian Morrow, Jennifer Nemeth-Seay, Ted Petley, Sam Wu, William R. Strohl, Anthony Simon Lynch, Victor J. Torres
Summary: Treating and preventing infections caused by antimicrobial-resistant bacterial pathogens is a global challenge. This study describes the development of a human-derived monoclonal antibody fusion protein that targets multiple bacterial adhesins, withstands bacterial protease degradation, avoids engagement with S. aureus IgG-binding proteins, and neutralizes pore-forming toxins. The fusion protein demonstrated enhanced immune functions and protection against S. aureus infections in preclinical animal models, suggesting its potential for clinical use.
CELL HOST & MICROBE
(2023)
Article
Microbiology
Emily L. Pruitt, Rutan Zhang, Dylan H. Ross, Nathaniel K. Ashford, Xi Chen, Francis Alonzo III, Matthew F. Bush, Brian J. Werth, Libin Xu
Summary: Staphylococcus aureus can synthesize fatty acids through its own pathway and also utilize host-derived fatty acids. This study investigated the substrate specificity of secreted lipases, the impact of human serum albumin and FASII inhibitor on fatty acid incorporation. It was found that Geh is the main lipase responsible for hydrolyzing cholesteryl esters, but other lipases can compensate for its function. The incorporation of exogenous fatty acids alters the lipidome, membrane fluidity, and ROS formation of S. aureus.
Article
Microbiology
Ifrah Shahi, Cristina N. Llaneras, Sofya S. Perelman, Victor J. Torres, Adam J. Ratner
Summary: This study conducted a CRISPR-Cas9 forward genetic screen to identify host genes involved in beta hc pore formation and cell death, but no clear candidate genes were found. The results suggest that beta hc may not require a single nonessential host factor for cell death.
MICROBIOLOGY SPECTRUM
(2022)