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 examined 323 mycobacterial Ldts and determined these enzymes cluster into six clades. We identified a variably represented yet distinct Ldt class (class 6) containing Mycobacterium smegmatis (Msm) LdtF and built a homology model of Msm LdtF toward elucidating class 6 structural and functional differences. We report class 6 Ldts have structurally divergent catalytic domains containing a 10-residue insertion near the active site and additionally determined that meropenem preferentially acylates LdtF. Our data demonstrate an evolutionary basis for mycobacterial Ldt multiplicity that lends support to the idea that paralogous Ldts serve nonredundant roles in vivo and suggests class 6 Ldts can be selectively targeted by specific carbapenem antibiotics.
journal_name
ACS Infect Disjournal_title
ACS infectious diseasesauthors
Zandi TA,Marshburn RL,Stateler PK,Brammer Basta LAdoi
10.1021/acsinfecdis.9b00234subject
Has Abstractpub_date
2019-12-13 00:00:00pages
2047-2054issue
12issn
2373-8227journal_volume
5pub_type
信件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
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abstract::The Burkholderia cepacia complex is a group of Gram-negative bacteria that are opportunistic pathogens in immunocompromised individuals, such as those with cystic fibrosis (CF) or chronic granulomatous disease (CGD). Burkholderia are intrinsically resistant to many antibiotics and the lack of antibiotic development ne...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.7b00235
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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::In December 2019, a novel beta (β) coronavirus eventually named SARS-CoV-2 emerged in Wuhan, Hubei province, China, causing an outbreak of severe and even fatal pneumonia in humans. The virus has spread very rapidly to many countries across the world, resulting in the World Health Organization (WHO) to declare a pande...
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pub_type: 杂志文章,评审
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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...
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pub_type: 杂志文章
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abstract::Boronic acid transition state inhibitors (BATSIs) are known reversible covalent inhibitors of serine β-lactamases. The selectivity and high potency of specific BATSIs bearing an amide side chain mimicking the β-lactam's amide side chain are an established and recognized synthetic strategy. Herein, we describe a new cl...
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doi:10.1021/acsinfecdis.0c00254
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abstract::Decreasing the therapeutic pipeline for vancomycin-resistant Enterococci (VRE) calls for novel strategies to enhance our antibacterial arsenal. Herein, we investigated the potential applications of surface localized antimicrobial display (SLAY)-derived cationic peptides in the fight against VanA operon mediated vancom...
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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
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abstract::Gram-negative bacteria are intrinsically resistant to many antibiotics. Species that have acquired multidrug resistance and cause infections that are effectively untreatable present a serious threat to public health. The problem is broadly recognized and tackled at both the fundamental and applied levels. This paper s...
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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...
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abstract::Neurotoxicity is an unwanted side effect for patients when receiving parenteral colistin therapy. The development of effective neuroprotective agents that can be coadministered during colistin therapy remains a priority area in antimicrobial chemotherapy. The present study aimed to investigate the protective effect of...
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更新日期:2020-06-12 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
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doi:10.1021/acsinfecdis.9b00128
更新日期:2019-10-11 00:00:00
abstract::In the field of Parkinson's disease (PD) research, leucine-rich repeat kinase 2 (LRRK2) remains one of the most enigmatic kinases. LRRK2 pathogenic mutations result in increased kinase activity, making LRRK2 an attractive therapeutic target for PD. For over 10 years, the identification of a bona fide substrate and a p...
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doi:10.1021/acsinfecdis.9b00051
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abstract::Negamycin is a hydrophilic antimicrobial translation inhibitor that crosses the lipophilic inner membrane of Escherichia coli via at least two transport routes to reach its intracellular target. In a minimal salts medium, negamycin's peptidic nature allows illicit entry via a high-affinity route by hijacking the Dpp d...
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doi:10.1021/acsinfecdis.5b00027
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abstract::Recent epidemiological studies have revealed that Porphyromonas gingivalis, a major pathogen in periodontal disease, is associated with the development of oral squamous cell carcinoma (OSCC). However, the underlying mechanisms induced by P. gingivalis have not been well-defined. We aimed to determine the role of P. gi...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00032
更新日期:2019-08-09 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...
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pub_type: 杂志文章,评审
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更新日期:2019-07-12 00:00:00
abstract::Stimulator of interferon genes (STING) is an integral ER-membrane protein that can be activated by 2'3'-cGAMP synthesized by cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) upon binding of double-stranded DNA. It activates interferon (IFN) and inflammatory cytokine responses to defend against in...
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doi:10.1021/acsinfecdis.9b00010
更新日期:2019-07-12 00:00:00
abstract::A method for the fast isolation, propagation, and characterization of very low count bacteriophages active against pathogenic bacterial strains is described in this study. Bacteriophages with a count of 102 phage particles were dynamically adhered from the maximum 10 mL blood plasma sample onto the nanostructured part...
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abstract::The maintenance of deoxyribonucleotide triphosphate (dNTP) homeostasis through synthesis and degradation is critical for accurate genomic and mitochondrial DNA replication fidelity. Trypanosoma brucei makes use of both the salvage and de novo pathways for the provision of pyrimidine dNTPs. In this respect, the sterile...
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abstract::MmpL3, an essential mycolate transporter in the inner membrane of Mycobacterium tuberculosis (Mtb), has been identified as a target of multiple, chemically diverse antitubercular drugs. However, several of these molecules seem to have secondary targets and inhibit bacterial growth by more than one mechanism. Here, we ...
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abstract::To explore the possibility of constrained peptides to target Plasmodium-infected cells, we designed a J domain mimetic derived from Plasmodium falciparum calcium-dependent protein kinase 1 ( PfCDPK1) as a strategy to disrupt J domain binding and inhibit PfCDPK1 activity. The J domain disruptor (JDD) peptide was confor...
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abstract::The fusion between the viral and the target cell membrane is a crucial step in the life cycle of enveloped viruses. The blocking of this process is a well-known therapeutic approach that led to the development of the fusion inhibitor peptide enfuvirtide, clinically used against human immunodeficiency virus (HIV) type ...
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更新日期:2019-04-12 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...
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doi:10.1021/acsinfecdis.7b00064
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abstract::Across zoonotic pathogens, RNA viruses are responsible for disproportionate levels of human disease, suffering, and death. Neurotropic RNA viruses (e.g., rabies, Japanese and Eastern Equine Encephalitis, Ebola, West Nile, Powassan) infect the brain and spinal cord, causing meningitis, encephalitis, microcephaly, and G...
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abstract::Protein S-palmitoylation is an important post-translational modification (PTM) in blood stages of the malaria parasite, Plasmodium falciparum. S-palmitoylation refers to reversible covalent modification of cysteine residues of proteins by saturated fatty acids. In vivo, palmitoylation is regulated by concerted activit...
journal_title:ACS infectious diseases
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abstract::Each year, infectious diseases are responsible for millions of deaths, most of which occur in the rural areas of developing countries. Many of the infectious disease diagnostic tools used today require a great deal of time, a laboratory setting, and trained personnel. Due to this, the need for effective point-of-care ...
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abstract::Emerging β-lactamase-mediated resistance is threatening the clinical utility of the single most prominent class of antibacterial agents used in medicine, the β-lactams. The diazabicyclooctane avibactam is able to inhibit a wider range of serine β-lactamases than has been previously observed with β-lactamase inhibitors...
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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...
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abstract::Brain-eating amoebae cause devastating infections in the central nervous system of humans, resulting in a mortality rate of 95%. There are limited effective therapeutic options available clinically for treating granulomatous amoebic encephalitis and primary amoebic meningoencephalitis caused by Acanthamoeba castellani...
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doi:10.1021/acsinfecdis.9b00263
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