Article
Immunology
Sara E. Oliver, Amy B. Rubis, Heidi M. Soeters, Arthur Reingold, Meghan Barnes, Susan Petit, Monica M. Farley, Lee H. Harrison, Kathy Como-Sabetti, Sarah A. Khanlian, Rachel Wester, Ann Thomas, William Schaffner, Henju Marjuki, Xin Wang, Susan Hariri
Summary: This study evaluated the epidemiology of NTHi disease in the US, including among pregnant women, infants, and PWH. Results showed that NTHi causes substantial invasive disease, especially among older adults, pregnant/postpartum women, and neonates. Enhanced surveillance and targeted interventions are needed to prevent perinatal NTHi infections.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Immunology
Sharon L. Clark, Elke J. Seppanen, Lea-Ann S. Kirkham, Laura A. Novotny, Lauren O. Bakaletz, Allan W. Cripps, Karli Corscadden, Harvey Coates, Shyan Vijayasekaran, Peter C. Richmond, Ruth B. Thornton
Summary: The study found that Australian Aboriginal children with chronic and recurrent otitis media had lower serum IgG titers to non-typeable Haemophilus influenzae (NTHi) protein vaccine candidate antigens, suggesting a reduced ability to develop persistent IgG responses due to repeated exposure to various bacterial strains.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Seth P. Jones, Kali H. Cook, Melody L. Holmquist, Liam J. Almekinder, Annie M. Delaney, Ryhl Charles, Natalie Labbe, Janai Perdue, Niaya Jackson, Michael E. Pichichero, Ravinder Kaur, Lea Michel, Michael L. Gleghorn
Summary: We have determined the crystal structure of nonlipidated nontypeable Haemophilus influenzae protein D and compared it with E. coli GlpQ. The structures exhibit similar homodimer organization and the active site of protein D is located in the triose-phosphate isomerase barrel domain. This study is important for understanding the interaction of protein D with substrates and for designing inhibitors.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Immunology
Naoko Fuji, Michael Pichichero, Ravinder Kaur
Summary: This study found that the prevalence of Haemophilus influenzae in the nasopharynx of young children is very low during health periods, but is high in middle ear fluid at the onset of acute otitis media (AOM). Nontypeable H. influenzae accounts for over 90% of all isolates, with type f being the most prevalent among encapsulated strains. Beta-lactamase production and antibiotic nonsusceptibility are common among H. influenzae strains isolated from the nasopharynx and middle ear fluid.
PEDIATRIC INFECTIOUS DISEASE JOURNAL
(2021)
Article
Multidisciplinary Sciences
Nadia A. Kadry, Eric A. Porsch, Hao Shen, Joseph W. St Geme
Summary: NTHi is a common cause of respiratory tract disease and preventing colonization is a strategy to prevent disease. Immunization with HMW1 and HMW2 can protect against colonization by both parent NTHi strain and heterologous strains expressing distinct HMW1 and HMW2 proteins. The protection against heterologous strains is IL-17A dependent.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Nader Shaikh, Alejandro Hoberman, Jack L. L. Paradise, Howard E. E. Rockette, Marcia Kurs-Lasky, Judith M. M. Martin
Summary: Through two separate clinical trials, we found that young children aged 6-23 months without nasopharyngeal colonization of either Streptococcus pneumoniae or Haemophilus influenzae may not need or can have a shortened duration of antibiotic treatment.
PEDIATRIC INFECTIOUS DISEASE JOURNAL
(2023)
Article
Immunology
Osama Abdel-Razek, Tianyi Liu, Xinghua Chen, Qiushi Wang, Gautam Vanga, Guirong Wang
Summary: This study investigated the role of surfactant protein D (SP-D) in non-typeable Haemophilus influenzae (NTHi)-induced otitis media (OM) in mice. The results showed that SP-D plays a critical role in enhancing host defense and regulating inflammatory responses in the experimental OM mice model.
JOURNAL OF INNATE IMMUNITY
(2021)
Article
Multidisciplinary Sciences
Lei Xu, Joshua Earl, Michael E. Pichichero
Summary: Analysis of microbiota composition in the nasopharynx of children revealed correlations between certain genera and Streptococcus pneumoniae colonization, with Corynebacterium showing a consistent inverse relationship. Corynebacterium propinquum and C. pseudodiphtheriticum were found to inhibit the growth of Spn serotype 22F strain in vitro.
Article
Chemistry, Medicinal
Hongmao Sun, Nathan P. Coussens, Carina Danchik, Leah M. Wachsmuth, Mark J. Henderson, Samarjit Patnaik, Matthew D. Hall, Ashley L. Molinaro, Dayle A. Daines, Min Shen
Summary: This study identified potential inhibitors of NTHi VapC1 ribonuclease through virtual screening and scaffold hopping. These inhibitors could serve as starting points for preclinical development.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Review
Immunology
Martina Janouskova, Megan Laura Straw, Yu-Ching Su, Kristian Riesbeck
Summary: This review discusses the multifaceted gene regulation mechanisms employed by S. pneumoniae, H. influenzae, and M. catarrhalis during middle ear infection. Through phase variation- and quorum sensing-dependent gene regulation, these pathogens control their virulence phenotypes for survival and host adaptation. Understanding the gene expression regulation mechanisms during the onset of OM may lead to the development of new antimicrobial agents to combat antimicrobial resistance.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Chinh C. Ngo, Helen M. Massa, Brent A. McMonagle, Christopher F. Perry, Michael D. Nissen, Theo P. Sloots, Ruth B. Thornton, Allan W. Cripps
Summary: This study identified Streptococcus pneumoniae, non-typeable Haemophilus influenzae (NTHi), and rhinovirus as the predominant bacteria and viruses in the upper respiratory tract of children in South-East Queensland, Australia, with and without a clinical history of otitis media. The presence of bacterial otopathogens within the middle ear was found to be more predictive of concurrent upper respiratory tract infection than viruses. The study also confirmed the complex polymicrobial environment within adenoid tissues in children, regardless of otitis media history.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Timothy F. Murphy, Charmaine Kirkham, Adonis D'Mello, Sanjay Sethi, Melinda M. Pettigrew, Herve Tettelin
Summary: Chronic obstructive pulmonary disease (COPD) is a common and debilitating disorder that is the third leading cause of death worldwide. This study analyzed the persistence of nontypeable Haemophilus influenzae (NTHi) in COPD airways and found that the NTHi genome undergoes inversion during persistence, resulting in changes in expression of key virulence factors. It was also discovered that the adhesins HMW1 and HMW2 play a critical role in NTHi adherence and invasion of respiratory epithelial cells. These findings provide important insights into the mechanisms of NTHi persistence in COPD airways and may inform the development of novel interventions.
Article
Biochemistry & Molecular Biology
Lea V. Michel, Ravinder Kaur, Michael L. Gleghorn, Melody Holmquist, Karin Pryharski, Janai Perdue, Seth P. Jones, Niaya Jackson, Isabelle Pilo, Anna Kasper, Natalie Labbe, Michael Pichichero
Summary: Nontypeable Haemophilus influenzae (NTHi) is a dominant pathogen causing infections such as acute otitis media and acute sinusitis. Developing a vaccine to protect against NTHi infection is urgently needed. Previous research shows that protein D (PD), outer membrane protein (OMP) 26, and Protein 6 (P6) are potential vaccine candidates. However, when PD and OMP26 were combined into a single vaccine formulation, PD antibody levels were significantly lower. The mechanism behind this effect needs further study.
Article
Infectious Diseases
Zein Assad, Robert Cohen, Emmanuelle Varon, Corinne Levy, Stephane Bechet, Francois Corrard, Andreas Werner, Naim Ouldali, Stephane Bonacorsi, Alexis Rybak
Summary: This study analyzed the evolution of beta-lactam resistance in Haemophilus influenzae strains isolated from children with acute otitis media in France. The proportion of beta-lactamase-producing and beta-lactamase-negative, ampicillin-resistant Hi strains remained stable over time in nasopharyngeal carriage and mild ear fluid samples. Therefore, amoxicillin remains a valid recommendation as the first-line drug for childhood acute otitis media in France.
Article
Pediatrics
Grigorios Chatziparasidis, Ahmad Kantar, Keith Grimwood
Summary: The respiratory tract antimicrobial defense system protects the lungs from microorganisms through various defense mechanisms. Nontypeable Haemophilus influenzae (NTHi), a potential pathogen, uses multiple strategies to colonize the lower airways and establish persistent infections. NTHi impairs mucociliary clearance, evades host defenses, and forms biofilms, causing chronic infections and inflammation. Understanding the molecular pathogenesis of NTHi is important for developing effective therapies and vaccines, considering its genetic heterogeneity. Currently, there are no vaccine candidates ready for large clinical trials.
PEDIATRIC PULMONOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Valerie Sgheiza, Bethany Novick, Sarah Stanton, Jeanetta Pierce, Breanne Kalmeta, Melody Frink Holmquist, Kyle Grimaldi, Kara L. Bren, Lea Vacca Michel
Editorial Material
Multidisciplinary Sciences
Virginia Gewin, Bryan Gaensler, Dorceta Taylor, Ijeoma Uchegbu, Ersilia Vaudo Scarpetta, Lea Michel, Gill Valentine
Article
Infectious Diseases
Lea Vacca Michel, Leslie Gallardo, Anna Konovalova, Morgan Bauer, Niaya Jackson, Mark Zavorin, Carlie McNamara, Jeanetta Pierce, Susan Cheng, Emma Snyder, Judith Hellman, Michael E. Pichichero
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2020)
Article
Biochemistry & Molecular Biology
Lea V. Michel, Ravinder Kaur, Michael L. Gleghorn, Melody Holmquist, Karin Pryharski, Janai Perdue, Seth P. Jones, Niaya Jackson, Isabelle Pilo, Anna Kasper, Natalie Labbe, Michael Pichichero
Summary: Nontypeable Haemophilus influenzae (NTHi) is a dominant pathogen causing infections such as acute otitis media and acute sinusitis. Developing a vaccine to protect against NTHi infection is urgently needed. Previous research shows that protein D (PD), outer membrane protein (OMP) 26, and Protein 6 (P6) are potential vaccine candidates. However, when PD and OMP26 were combined into a single vaccine formulation, PD antibody levels were significantly lower. The mechanism behind this effect needs further study.
Meeting Abstract
Chemistry, Multidisciplinary
Aaron Fadden, Julia Faraone, Katharine Umphred-Wilson, Meghan O'Neil, Jeff Mills, George Thurston, Lea Vacca Michel
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
(2018)
Meeting Abstract
Chemistry, Multidisciplinary
Xinbei Liu, Sean Lewis, Sarah Stanton, Ciara LaClair, Shivani Phadke, Lea Vacca Michel
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
(2018)
Meeting Abstract
Biochemistry & Molecular Biology
Emma Snyder, Mark Zavorin, Kara Farquaharson, Nicole Panullo, Michael Pichichero, Judith Hellman, Lea Vacca Michel
Meeting Abstract
Biochemistry & Molecular Biology
Meghan O'Neil, Ciara LaClair, Mark Zavorin, Karin Pryharski, Nadeem Khan, Ravinder Kaur, Michael Pichichero, Lea Vacca Michel
Meeting Abstract
Biochemistry & Molecular Biology
Nicole Pannullo, Mark Zavorin, Brooke D'Arcy, Kara Farquharson, Ravinder Kaur, Naveen Surendran, Michael Pichichero, Judith Hellman, Lea Vacca Michel
Meeting Abstract
Biochemistry & Molecular Biology
Nicole Fernandez, Carlie McNamara, Michael Pichichero, Judith Hellman, Lea Michel
Meeting Abstract
Biochemistry & Molecular Biology
Austin U. Gehret, Jessica W. Trussell, Lea V. Michel
Meeting Abstract
Biochemistry & Molecular Biology
Sarah Stanton, Jeanetta Pierce, Valerie Sgheiza, Kara L. Bren, Lea Michel
Meeting Abstract
Biochemistry & Molecular Biology
Katharine Umphred-Wilson, Aaron Fadden, John Zanet, Kaylee Mathews, George Thurston, Jeffrey Mills, Lea Vacca Michel
Meeting Abstract
Biochemistry & Molecular Biology
Shivani Phadke, Sarah Stanton, Jeanetta Pierce, Clara LaClair, Cianna Hall, Lea Michel