Abstract:
:Subunit vaccines composed of protein antigens covalently attached to Toll-like receptor (TLR) agonists elicit superior immune responses compared to mixtures of antigens and TLR agonists. Among different conjugation approaches, enzyme-mediated ligation is one of the few that provides an opportunity for the generation of homogeneous, molecularly defined products in which protein antigens are maintained with native structures, which is most critical to elicit protective immune responses upon vaccination. Four highly conserved protein antigens from Group A Streptococcus (GAS) have the potential to be safe and efficacious vaccine candidates. After a TLR2 agonist fibroblast-stimulating lipopeptide-1 (FSL-1) was successfully attached onto each antigen using sortase A and techniques for their purification were developed, a combination vaccine containing interleukin 8 (IL-8) protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP]), Group A Streptococcal C5a peptidase (SCPA), anchorless virulence factor arginine deiminase (ADI), and trigger factor (TF)-TLR2 conjugates was produced. This combination was assessed for immunity in mice and compared with mixtures of the four antigens with FSL-1 or alum. High titer antigen-specific IgG antibodies were detected from all vaccine groups, with antibodies elicited from FSL-1 conjugates around 10-fold higher compared to the FSL-1 mixture group. Furthermore, the FSL-1 conjugates afforded a more balanced TH1/TH2 immune response than the alum-adjuvanted group, suggesting that this combination vaccine represents a promising candidate for the prevention of GAS diseases. Thus, we established a conjugation platform that allows for the production of defined, site-specific antigen-adjuvant conjugates, which maintain the native three-dimensional structure of antigens and can be potentially applied to a variety of protein antigens.
journal_name
ACS Infect Disjournal_title
ACS infectious diseasesauthors
Xu Z,Rivera-Hernandez T,Moyle PMdoi
10.1021/acsinfecdis.0c00047subject
Has Abstractpub_date
2020-07-10 00:00:00pages
1770-1782issue
7issn
2373-8227journal_volume
6pub_type
杂志文章abstract::Violacein is a tryptophan-derived purple pigment produced by environmental bacteria, which displays multiple biological activities, including strong inhibition of Gram-positive pathogens. Here, we applied a combination of experimental approaches to identify the mechanism by which violacein kills Gram-positive bacteria...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00245
更新日期:2019-04-12 00:00:00
abstract::Conventional antibiotics are not effective in treating infections caused by drug-resistant or persistent nongrowing bacteria, creating a dire need for the development of new antibiotics. We report that the small molecule nTZDpa, previously characterized as a nonthiazolidinedione peroxisome proliferator-activated recep...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00161
更新日期:2018-11-09 00:00:00
abstract::Innate and developed resistance mechanisms of bacteria to antibiotics are obstacles in the design of novel drugs. However, antibacterial prodrugs and conjugates have shown promise in circumventing resistance and tolerance mechanisms via directed delivery of antibiotics to the site of infection or to specific species o...
journal_title:ACS infectious diseases
pub_type: 杂志文章,评审
doi:10.1021/acsinfecdis.9b00019
更新日期:2019-06-14 00:00:00
abstract::A series of derivatives of the 4,5-disubstituted class of 2-deoxystreptamine aminoglycoside antibiotics neomycin, paromomycin, and ribostamycin was prepared and assayed for (i) their ability to inhibit protein synthesis by bacterial ribosomes and by engineered bacterial ribosomes carrying eukaryotic decoding A sites, ...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00128
更新日期:2019-10-11 00:00:00
abstract::Zika virus (ZIKV) infection has caused global concern because of its association with fetal microcephaly and serious neurological complications in adults since 2016. Currently, no specific anti-ZIKV therapy is available to control ZIKV infection. During the last couple of years, the intensive investigation of ZIKV str...
journal_title:ACS infectious diseases
pub_type: 杂志文章,评审
doi:10.1021/acsinfecdis.9b00047
更新日期:2019-07-12 00:00:00
abstract::Metallo-β-lactamases (MBLs) are a growing threat to the continued efficacy of β-lactam antibiotics. Recently, aspergillomarasmine A (AMA) was identified as an MBL inhibitor, but the mode of inhibition was not fully characterized. Equilibrium dialysis and metal analysis studies revealed that 2 equiv of AMA effectively ...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.7b00106
更新日期:2018-02-09 00:00:00
abstract::Burkholderia multivorans is a significant health threat to persons with cystic fibrosis (CF). Infections are difficult to treat as this pathogen is inherently resistant to multiple antibiotics. Susceptibility testing of isolates obtained from CF respiratory cultures revealed that single agents selected from different ...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.7b00020
更新日期:2017-07-14 00:00:00
abstract::Chronic hepatitis B virus (HBV) infection remains a major cause of morbidity and mortality worldwide. HBV surface antigen loss is considered a functional cure and is an ideal goal for antiviral therapy. However, current treatment regimens, including nucleos(t)ide analogues or interferons monotherapy and combination th...
journal_title:ACS infectious diseases
pub_type: 杂志文章,评审
doi:10.1021/acsinfecdis.8b00297
更新日期:2019-05-10 00:00:00
abstract::Human African trypanosomiasis (HAT) is a fatal infectious disease caused by the eukaryotic pathogen Trypanosoma brucei (Tb). Available treatments are difficult to administer and have significant safety issues. S-Adenosylmethionine decarboxylase (AdoMetDC) is an essential enzyme in the parasite polyamine biosynthetic p...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.7b00022
更新日期:2017-07-14 00:00:00
abstract::Multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis are resistant to first- and second-line drug regimens and resulted in 210,000 fatalities in 2013. In the current study, we screened a library of aquatic bacterial natural product fractions for their ability to inhibit this pathogen. A frac...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.5b00005
更新日期:2015-04-10 00:00:00
abstract::Many viruses, including the hepatitis C virus (HCV), are dependent on the host RNA silencing pathway for replication. In this study, we screened small molecule probes, previously reported to disrupt loading of the RNA-induced silencing complex (RISC), including 6-hydroxydopamine (6-OHDA), suramin (SUR), and aurintrica...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.6b00098
更新日期:2016-11-11 00:00:00
abstract::Daptomycin is a calcium-dependent lipopeptide antibiotic that is used clinically against various Gram-positive pathogens. It acts on bacterial cell membranes, whose susceptibility varies with the content of phosphatidylglycerol (PG). Some studies have reported that daptomycin permeabilizes and depolarizes bacterial ce...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.7b00138
更新日期:2017-11-10 00:00:00
abstract::Streptococcus mutans ( S. mutans) is a Gram-positive human pathogen that is one of the major contributors to dental caries, a condition with an economic cost of over $100 billion per year in the United States. S. mutans secretes a 21-amino-acid peptide termed the competence stimulating peptide (21-CSP) to assess its p...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00115
更新日期:2018-09-14 00:00:00
abstract::Vaccines and antivirals to combat dengue, Zika, and other flavivirus pathogens present a major, unmet medical need. Vaccine development has been severely challenged by the antigenic diversity of these viruses and the propensity of non-neutralizing, cross-reactive antibodies to facilitate cellular infection and increas...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00322
更新日期:2019-03-08 00:00:00
abstract::The current explosive epidemic of Zika virus in South and Central America, as well as the Caribbean, poses a global public health emergency. Here we comment on the challenges on development of better diagnosis and potential therapeutics and vaccine for Zika virus. ...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.6b00030
更新日期:2016-03-11 00:00:00
abstract::Recent studies on 3,6-diphenylated imidazopyridazines have demonstrated impressive in vitro activity and in vivo efficacy in mouse models of malaria infection. Herein, we report the synthesis and antiplasmodium evaluation of a new series of amidated analogues and demonstrate that these compounds potently inhibit Plasm...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.0c00481
更新日期:2021-01-08 00:00:00
abstract::Amonabactins are a group of four related catecholate siderophores produced by several species of the genus Aeromonas, including A. hydrophila and the fish pathogen A. salmonicida subsp. salmonicida. Although the gene cluster encoding amonabactin biosynthesis also contains a gene that could encode the ferri-siderophore...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00274
更新日期:2019-11-08 00:00:00
abstract::Individuals who exhibit long-term HIV suppression and CD4 T-cell preservation without antiretroviral therapy are of great interest for HIV research. There is currently no robust method for rapid identification of these "HIV controller" subjects; however, HLA-B*57 (human leukocyte antigen (major histocompatibility comp...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.7b00042
更新日期:2017-12-08 00:00:00
abstract::Hypervirulent Klebsiella pneumoniae (hvKp) is an underrecognized pathotype of K. pneumoniae since the majority of cases have occurred in East Asia. However, hvKp is a public health threat due to its ability to infect healthy individuals, ongoing dissemination, and acquisition of resistance determinants. hvKp-directed ...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00117
更新日期:2019-07-12 00:00:00
abstract::Because of its essential role as a bacterial virulence factor, enzyme sortase A (SrtA) has become an attractive target for the development of new antivirulence drugs against Gram-positive infections. Here we describe 27 compounds identified as covalent inhibitors of Staphylococcus aureus SrtA by screening a library of...
journal_title:ACS infectious diseases
pub_type: 信件
doi:10.1021/acsinfecdis.9b00265
更新日期:2020-02-14 00:00:00
abstract::The α-Gal antigen [Galα(1,3)Galβ(1,4)GlcNAcα] is an immunodominant epitope displayed by infective trypomastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. A virus-like particle displaying a high density of α-Gal was found to be a superior reagent for the ELISA-based serological diagnosis of Ch...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.6b00114
更新日期:2016-12-09 00:00:00
abstract::Coronaviruses first garnered widespread attention in 2002 when the severe acute respiratory syndrome coronavirus (SARS-CoV) emerged from bats in China and rapidly spread in human populations. Since then, Middle East respiratory syndrome coronavirus (MERS-CoV) emerged and still actively infects humans. The recent SARS-...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.0c00491
更新日期:2020-10-06 00:00:00
abstract::MurG (uridine diphosphate-N-acetylglucosamine/N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase) is an essential bacterial glycosyltransferase that catalyzes the N-acetylglucosamine (GlcNAc) transformation of lipid I to lipid II during peptidoglycan biosynthesis. Park's nucleot...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00242
更新日期:2020-06-12 00:00:00
abstract::Antibiotic resistance can come at a high cost, both in terms of fitness for the pathogen and poorer outcomes for patients. The fitness landscape encountered by bacterial pathogens varies greatly throughout patient populations in terms of host immunity as well as the duration and spectrum of antibiotics encountered. Se...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00158
更新日期:2018-09-14 00:00:00
abstract::Ebola virus (EBOV), a member of the family Filoviridae, is a nonsegmented negative-sense RNA virus that causes severe, often lethal, disease in humans. EBOV RNA synthesis is carried out by a complex that includes several viral proteins. The function of this machinery is essential for viral gene expression and viral re...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.5b00053
更新日期:2015-08-14 00:00:00
abstract::Bacterial coinfection in COVID-19 patients has the potential to complicate treatments and accelerate the development of antibiotic resistance in the clinic due to the widespread use of broad-spectrum antibiotics, including in Indonesia. The surge of COVID-19 patients may worsen antibiotic overuse; therefore, informati...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.1c00006
更新日期:2021-01-27 00:00:00
abstract::Poor patient adherence to antiretroviral medication represents a major obstacle for managing disease and reducing rates of new HIV infections. The measurement of patient drug levels is the most objective method of determining adherence. Tenofovir and tenofovir diphosphate are metabolites of some of the most common HIV...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.0c00010
更新日期:2020-07-10 00:00:00
abstract::Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial pathogen that causes invasive infections in both children and adults. During pregnancy, GBS is a significant cause of infection of the fetal membranes (chorioamnionitis), which can lead to intra-amniotic infection, preterm birth, stillb...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.7b00064
更新日期:2017-08-11 00:00:00
abstract::The genomes of diverse mycobacterial species encode multiple proteins with the canonical l,d-transpeptidase (Ldt) sequence motif. The reason for this apparent redundancy is not well understood, but evidence suggests paralogous Ldts may serve niche roles in maintaining and/or remodeling mycobacterial peptidoglycan. We ...
journal_title:ACS infectious diseases
pub_type: 信件
doi:10.1021/acsinfecdis.9b00234
更新日期:2019-12-13 00:00:00
abstract::Evolving antimicrobial resistance has motivated the search for novel targets and alternative therapies. Caseinolytic protease (ClpP) has emerged as an enticing new target since its function is conserved and essential for bacterial fitness, and because its inhibition or dysregulation leads to bacterial cell death. ClpP...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.0c00599
更新日期:2020-12-11 00:00:00