Whole Genome Sequencing Identifies Novel Mutations Associated With Bedaquiline Resistance in Mycobacterium tuberculosis
Bedaquiline (BDQ), a new antitubercular agent, has been used to treat drug-resistant tuberculosis (TB). Although mutations in atpE, rv0678, and pepQ confer major resistance to BDQ, the mechanisms of resistance to BDQ in vitro and in clinical settings have not been fully elucidated. We selected BDQ-resistant mutants from 7H10 agar plates containing 0.5 mg/L BDQ (the critical concentration) and identified mutations associated with BDQ resistance through whole genome sequencing and Sanger sequencing. A total of 1,025 mutants were resistant to BDQ. We randomly selected 168 mutants for further analysis and discovered that 157/1...
Source: Frontiers in cellular and infection microbiology - May 27, 2022 Category: Microbiology Source Type: research

Rare Variants in Inborn Errors of Immunity Genes Associated With Covid-19 Severity
Host genetic factors have been shown to play an important role in SARS-CoV-2 infection and the course of Covid-19 disease. The genetic contributions of common variants influencing Covid-19 susceptibility and severity have been extensively studied in diverse populations. However, the studies of rare genetic defects arising from inborn errors of immunity (IEI) are relatively few, especially in the Chinese population. To fill this gap, we used a deeply sequenced dataset of nearly 500 patients, all of Chinese descent, to investigate putative functional rare variants. Specifically, we annotated rare variants in our call set and...
Source: Frontiers in cellular and infection microbiology - May 27, 2022 Category: Microbiology Source Type: research

Contribution of Puma to Inflammatory Resolution During Early Pneumococcal Pneumonia
Apoptosis of cells at the site of infection is a requirement for shutdown of inflammatory signaling, avoiding tissue damage, and preventing progression of sepsis. Puma+/+ and Puma-/- mice were challenged with TIGR4 strain pneumococcus and cytokines were quantitated from lungs and blood using a magnetic bead panel analysis. Puma-/- mice exhibited higher lung and blood cytokine levels of several major inflammatory cytokines, including IL-6, G-CSF, RANTES, IL-12, IFN-ϒ, and IP-10. Puma-/- mice were more susceptible to bacterial dissemination and exhibited more weight loss than their wild-type counterparts. RNA sequencing ana...
Source: Frontiers in cellular and infection microbiology - May 26, 2022 Category: Microbiology Source Type: research

Intestinal Alkaline Phosphatase Prevents Sulfate Reducing Bacteria-Induced Increased Tight Junction Permeability by Inhibiting Snail Pathway
Tight junctions (TJs) are essential components of intestinal barrier integrity and protect the epithelium against passive paracellular flux and microbial translocation. Dysfunctional TJ leads to leaky gut, a condition associated with diseases including inflammatory bowel disease (IBD). Sulfate-Reducing Bacteria (SRB) are minor residents of the gut. An increased number of Desulfovibrio, the most predominant SRB, is observed in IBD and other diseases associated with leaky gut. However, it is not known whether Desulfovibrio contributes to leaky gut. We tested the hypothesis that Desulfovibrio vulgaris (DSV) may induce intesti...
Source: Frontiers in cellular and infection microbiology - May 26, 2022 Category: Microbiology Source Type: research

Editorial: Insights in Clinical Microbiology: 2021
(Source: Frontiers in cellular and infection microbiology)
Source: Frontiers in cellular and infection microbiology - May 25, 2022 Category: Microbiology Source Type: research

Fast, Simple, and Highly Specific Molecular Detection of Porphyromonas gingivalis Using Isothermal Amplification and Lateral Flow Strip Methods
Porphyromonas gingivalis is an important oral pathogen that causes periodontal disease and is difficult to culture under conventional conditions. Therefore, a reliable technique for detecting this pathogenic bacterium is required. Here, isothermal recombinase polymerase amplification (RPA), a new nucleic acid amplification method, was combined with a visualization method based on nanoparticle-based lateral flow strips (LFS) for the rapid detection of P. gingivalis. The species-specific 16S rRNA sequence of P. gingivalis was used as the target for RPA, and a set of specific primer–probe combinations were designed and scre...
Source: Frontiers in cellular and infection microbiology - May 25, 2022 Category: Microbiology Source Type: research

The Phosphodiesterase Inhibitor Tadalafil Promotes Splenic Retention of Plasmodium falciparum Gametocytes in Humanized Mice
The persistence of erythrocytes infected with Plasmodium falciparum gametocytes in the bloodstream is closely related to the modulation of their mechanical properties. New drugs that increase the stiffness of infected erythrocytes may thus represent a novel approach to block malaria parasite transmission. The phosphodiesterase inhibitor tadalafil has been shown to impair the ability of infected erythrocytes to circulate in an in vitro model for splenic retention. Here, we used a humanized mouse model to address in vivo the effect of tadalafil on the circulation kinetics of mature gametocyte-infected erythrocytes. We show t...
Source: Frontiers in cellular and infection microbiology - May 25, 2022 Category: Microbiology Source Type: research

The Potential Association of Delayed T Lymphocyte Reconstitution Within Six Months Post-Transplantation With the Risk of Cytomegalovirus Retinitis in Severe Aplastic Anemia Recipients
ConclusionsIt is not enough to develop fundus screening strategies by merely relying on the CMV serostatus of recipients. Dynamic and continuous monitoring of T lymphocyte subsets, especially within six months post-HSCT, as well as serum immunoglobulin levels, can provide assistance with screening program of CMVR in HSCT recipients with severe aplastic anemia. (Source: Frontiers in cellular and infection microbiology)
Source: Frontiers in cellular and infection microbiology - May 25, 2022 Category: Microbiology Source Type: research

Targeting the Plasmodium falciparum ’s Thymidylate Monophosphate Kinase for the Identification of Novel Antimalarial Natural Compounds
Recent reports of resistance to artemisinin-based combination drugs necessitate the need to discover novel antimalarial compounds. The present study was aimed at identifying novel antimalarial compounds from natural product libraries using computational methods. Plasmodium falciparum is highly dependent on the pyrimidine biosynthetic pathway, a de novo pathway responsible for the production of pyrimidines, and the parasite lacks the pyrimidine salvage enzymes. The P. falciparum thymidylate monophosphate kinase (PfTMPK) is an important protein necessary for rapid DNA replication; however, due to its broad substrate specific...
Source: Frontiers in cellular and infection microbiology - May 25, 2022 Category: Microbiology Source Type: research

Application of CRISPR/Cas Genomic Editing Tools for HIV Therapy: Toward Precise Modifications and Multilevel Protection
Although highly active antiretroviral therapy (HAART) can robustly control human immunodeficiency virus (HIV) infection, the existence of latent HIV in a form of proviral DNA integrated into the host genome makes the virus insensitive to HAART. This requires patients to adhere to HAART for a lifetime, often leading to drug toxicity or viral resistance to therapy. Current genome-editing technologies offer different strategies to reduce the latent HIV reservoir in the body. In this review, we systematize the research on CRISPR/Cas-based anti-HIV therapeutic methods, discuss problems related to viral escape and gene editing, ...
Source: Frontiers in cellular and infection microbiology - May 25, 2022 Category: Microbiology Source Type: research

Detangling the Crosstalk Between Ascaris, Trichuris and Gut Microbiota: What ´s Next?
Helminth infections remain a global public health issue, particularly in low- and middle-income countries, where roundworms from theTrichuris and Ascaris genera are most prevalent. These geohelminths not only impact human health but most importantly also affect animal well-being, in particular the swine industry. Host-helminth parasite interactions are complex and at the same time essential to understand the biology, dynamics and pathophysiology of these infections. Within these interactions, the immunomodulatory capacity of these helminths in the host has been extensively studied. Moreover, in recent years a growing inter...
Source: Frontiers in cellular and infection microbiology - May 25, 2022 Category: Microbiology Source Type: research

Fungal Infections as an Uprising Threat to Human Health: Chemosensitization of Fungal Pathogens With AFP From Aspergillus giganteus
Occurrence and intensity of systemic invasive fungal infections have significantly risen in recent decades with large amount of mortality and morbidity rates at global level. Treatment therapy lies on the current antifungal interventions and are often limited due to the emergence of resistance to antifungal agents. Chemosensitization of fungal strains to the conventional antimycotic drugs are of growing concern. Current antifungal drugs often have been reported with poor activity and side effects to the host and have a few number of targets to manifest their efficacy on the pathogens. Indiscriminately, the aforementioned i...
Source: Frontiers in cellular and infection microbiology - May 25, 2022 Category: Microbiology Source Type: research

Editorial: Host/Parasite Molecular and Cellular Interactions in the Establishment and Maintenance of Protozoan Infections
(Source: Frontiers in cellular and infection microbiology)
Source: Frontiers in cellular and infection microbiology - May 24, 2022 Category: Microbiology Source Type: research

The MtZ Strain: Molecular Characteristics and Outbreak Investigation of the Most Successful Mycobacterium tuberculosis Strain in Aragon Using Whole-Genome Sequencing
In conclusion, MtZ consists of several SNPs in genes related to virulence, pathogenesis, and survival, as well as other genomic polymorphisms, which may be implicated in its success among our population. (Source: Frontiers in cellular and infection microbiology)
Source: Frontiers in cellular and infection microbiology - May 24, 2022 Category: Microbiology Source Type: research

Experimental Models to Study the Pathogenesis of Malaria-Associated Acute Respiratory Distress Syndrome
Malaria-associated acute respiratory distress syndrome (MA-ARDS) is increasingly gaining recognition as a severe malaria complication because of poor prognostic outcomes, high lethality rate, and limited therapeutic interventions. Unfortunately, invasive clinical studies are challenging to conduct and yields insufficient mechanistic insights. These limitations have led to the development of suitable MA-ARDS experimental mouse models. In patients and mice, MA-ARDS is characterized by edematous lung, along with marked infiltration of inflammatory cells and damage of the alveolar-capillary barriers. Although, the pathogenic p...
Source: Frontiers in cellular and infection microbiology - May 23, 2022 Category: Microbiology Source Type: research