Meiosis in the human pathogen Aspergillus fumigatus has the highest known number of crossovers

Evidence from both population genetics and a laboratory sexual cycle indicate that sex is common in the fungus Aspergillus fumigatus. However, the impact of sexual reproduction has remained unclear. Here, we show that meiosis in A. fumigatus involves the highest known recombination rate, producing ~29 crossovers per chromosome. This represents the highest known crossover rate for any Eukaryotic species. We validate this recombination rate by mapping resistance to acriflavine, a common genetic marker. We further show that this recombination rate can produce the commonly encountered TR34/L98H azole-resistant cyp51A haplotype in each sexual event, facilitating its rapid and global spread. Understanding the consequences of this unparalleled crossover rate will not only enrich our genetic understanding of this emergent human pathogen, but of meiosis in general.

HCMV exploits STING signaling and counteracts IFN and ISG induction to facilitate dendritic cell infection

Human cytomegalovirus (HCMV) is a widespread obligatory human pathogen causing life-threatening disease in immunocompromised hosts. Myeloid cells such as monocyte-derived dendritic cells (moDCs) are targets of HCMV. Here, we performed single-cell RNA sequencing, which revealed infection of most moDCs upon in vitro HCMV exposure, whereas only a fraction of them initiated viral gene expression. We identified three moDC subsets, of which CD1a−/CD86− cells showed the highest susceptibility. Upon HCMV entry, STING activation not only induced IFN-β, but also promoted viral gene expression. Upon progression of infection, IFN-β but not IFN-λ1 expression was inhibited. Similarly, ISG expression was initially induced and then shut off and thus allowed productive infection. Increased viral gene expression was associated with the induction of several pro- (RHOB, HSP1A1, DNAJB1) and anti-viral (RNF213, TNFSF10, IFI16) genes. Thus, moDC permissiveness to HCMV depends on complex interactions between virus sensing, regulation of IFNs/ISGs and viral gene expression.

Structural basis of prokaryotic ubiquitin-like protein engagement and translocation by the mycobacterial Mpa-proteasome complex

Proteasomes are present in eukaryotes, archaea and Actinobacteria, including the human pathogen Mycobacterium tuberculosis, where proteasomal degradation supports persistence inside the host. In mycobacteria and other members of Actinobacteria, prokaryotic ubiquitin-like protein (Pup) serves as a degradation tag post-translationally conjugated to target proteins for their recruitment to the mycobacterial proteasome ATPase (Mpa). Here, we use single-particle cryo-electron microscopy to determine the structure of Mpa in complex with the 20S core particle at an early stage of pupylated substrate recruitment, shedding light on the mechanism of substrate translocation. Two conformational states of Mpa show how substrate is translocated stepwise towards the degradation chamber of the proteasome core particle. We also demonstrate, in vitro and in vivo, the importance of a structural feature in Mpa that allows formation of alternating charge-complementary interactions with the proteasome resulting in radial, rail-guided movements during the ATPase conformational cycle.

Genetic Characteristics and Microbiological Profile of Hypermucoviscous Multidrug-Resistant Klebsiella variicola Coproducing IMP-4 and NDM-1 Carbapenemases

As an important member of the Klebsiella pneumoniae complex, Klebsiella variicola is poorly studied as an emerging human pathogen. We, for the first time, report a unique K. variicola isolated from a pediatric patient in China.

The Protective Role of 1,8-Dihydroxynaphthalene–Melanin on Conidia of the Opportunistic Human Pathogen Aspergillus fumigatus Revisited: No Role in Protection against Hydrogen Peroxide and Superoxides

Opportunistic pathogens like Aspergillus fumigatus have strategies to protect themselves against reactive oxygen species like hydrogen peroxides and superoxides that are produced by immune cells. DHN-melanin is the green pigment on conidia of Aspergillus fumigatus and more than 2 decades ago was reported to protect conidia against hydrogen peroxide.

Prevalent of Staphylococcus aureus from Sachet Waters Sold in Different Areas of Jos Terminus Market, Nigeria

Staphylococcus aureus is an important human pathogen that causes wide range of infectious diseases both in nosocomial and community settings. The Gram-positive pathogen possess virulence factors that facilitate it to establish infections in the hosts. When a “water for life” is contaminated with infectious bacteria such as Staphylococcus aureus then, there may be public health challenge in the area. In this study Samples of Sachet water of different companies ware purchased, marked E, T, C and R and examined for the presence of staphylococcus aureus. Total of 80 sachet waters were examined and a prevalence rate of Staphylococcus aureus 5(25.00%) was recorded. The study revealed that sachet water (E) has the highest prevalence of 15.00%, followed by T (5%) and C (5%) and R had the least prevalence with 0.00%. It was discovered that a Prevalence rate of Abuja market terminus recorded 1(5.00%) while that of Ahmadu Bello way has the highest prevalence of 2(10.00%), Yan Taya market 1(5.00%) and railway 1(5.00%). This shows that S. aureus can be isolated from sachet waters. Though the sachet eaters had NAFDAC numbers, it is advisable to review and quality control such sachet water companies regularly because of Staphylococcus aureus and other public health infectious agants. The populace should equally be careful with the type of waters they drink.

A target engagement assay to assess uptake, potency and retention of antibiotics in living bacteria

A major challenge in antibiotics drug discovery is to turn potent biochemical inhibitors of essential bacterial components into effective antimicrobials. This difficulty is underpinned by a lack of methods to investigate the physicochemical properties needed for candidate antibiotics to permeate the bacterial cell envelope and avoid clearance by the action of bacterial efflux pumps. To address these issues, here we used a target engagement assay to measure the equilibrium and kinetics binding parameters of antibiotics to their molecular targets in live bacteria. We validated this approach for a known antibiotic target, dihydrofolate reductase, using the Gram-negative bacteria Escherichia coli and the emerging human pathogen Mycobacterium abscessus. We expect the use of similar target engagement assays to expedite the discovery and progression of novel, cell-permeable antibiotics with on-target activity.

Redirected Stress Responses in a Genome-Minimized ‘midi Bacillus ’ Strain with Enhanced Capacity for Protein Secretion

Our present study showcases a genome-minimized nonpathogenic bacterium, the so-called midi Bacillus , as a chassis for the development of future industrial strains that serve in the production of high-value difficult-to-produce proteins. In particular, we explain how midi Bacillus , which lacks about one-third of the original genome, effectively secretes a protein of the major human pathogen Staphylococcus aureus that cannot be produced by the parental Bacillus subtilis strain.

Seroprevalence of Anti-SARS-CoV-2 Antibodies in COVID-19 Patients in Hyderabad, Sindh

Aim: The world is affected by the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) pandemic. This virus has emerged as a human pathogen that can cause symptoms ranging from fever to Pneumonia, but it remains asymptomatic or mild. To better understand the virus's ongoing spread, identify those who have been infected, and track the immune response, accurate and robust immunological monitoring and SARS-CoV-2 detection assays are needed. Methods: The estimation of serology tests to assess the presence of antibodies to SARS-CoV-2 in COVID- 19 patients at Asian Institute of Medical Sciences (AIMS) and Isra University & hospital. 1229 patients were selected including males and females with the age being 25 to 65 years living in the territories from 1st August to 30th November 2020. The anti-SARS-CoV-2 test was performed by an electrochemiluminescence immunoassay analyzer. Results: Out of 1229 participants 206 (17%) were positive with COVID-19, and 1023 (83%) were negative. The results further revealed that a higher percentage of positive COVID-19 were detected in males in all age groups as compared to females, and most of them are affected at age of 46-65 years male 40 (24.69%) and female 14(17.5%). Conclusion: The seroprevalence of SARS-COV-2 antibodies has increased in the old age population, which may aid in determining the true number of infected cases. Although the current study is based on a small sample of participants, the findings suggest a study with a larger population to implement stronger and targeted interventions.