From sequence to function: Exploring biophysical properties of bacteriophage BFK20 lytic transglycosylase domain from the minor tail protein gp15.

Bacteriophages have evolved different mechanisms of infection and penetration of bacterial cell walls. In Siphoviridae-like viruses, the inner tail proteins have a pivotal role in these processes and often encode lytic protein domains which increase infection efficiency. A soluble lytic transglycosylase (SLT) domain was identified in the minor tail protein gp15 from the BFK20 bacteriophage. Six fragments containing this SLT domain with adjacent regions of different lengths were cloned, expressed and purified. The biophysical properties of the two best expressing fragments were characterized by nanoDSF and CD spectroscopy, which showed that both fragments had a high refolding ability of 90 %. 3D modeling indicated that the bacteriophage BFK20 SLT domain is structurally similar to lysozyme. The degradation activity of these SLT proteins was evaluated using a lysozyme activity assay. BFK20 might use its transglycosylase activity to allow efficient phage DNA entry into the host cell by degrading bacterial peptidoglycan.

Adapting nature's own solution: The effect of rhamnolipid and lytic bacteriophage cocktail on enteric pathogens that proliferate in mucilage.

The mucilage event witnessed in the Sea of Marmara in 2021 has emerged as a prominent environmental concern, capturing public attention due to its detrimental effects on ecological, economic, and aesthetic dimensions. Addressing the multifaceted impacts of mucilage demands a nature-centric scientific approach, given its global ramifications spanning economy, public health, international relations, and tourism. Consequently, this study sought to explore alternative approaches for the removal of pathogenic enteric bacteria associated with mucilage occurrences, diverging from conventional methodologies. Specifically, the primary objective was to assess the efficacy of rhamnolipid and a bacteriophage cocktail in mitigating the proliferation of enteric pathogens within mucilaginous environments. During the study, 91 phage isolations were obtained from 45 water samples taken and 10 phages were selected for the broad host range and because of the efficacy tests, a phage cocktail was created with 5 phages. It was found that the mixture of rhamnolipid, phage cocktail and rhamnolipid-phage cocktail reduced bacterial load by 7-9 log10, 9-12 log10 and 9-11 log10 respectively under laboratory conditions. When the study was carried out in seawater, reductions of 4-5 log10, 3 log10 and 4 log10 were achieved. This study has shown that the combined use of rhamnolipid, phage cocktail and rhamnolipid-phage cocktail can be considered as the most effective natural solution proposal for reducing bacterial load, both in laboratory conditions and in sea surface water.

Renal Mucormycosis with Disseminated Lytic Bony Lesions.

Renal Mucormycosis is a lethal opportunistic infection with extensive tissue invasion leading to infarction. We report a diabetic lady with disseminated fungal pyelonephritis presenting with extensive lytic bony lesions mimicking malignancy. Prompt initiation of antifungal therapy and surgical debridement is the key to successful management. A clinician should have a high index of suspicion for Mucormycosis in a patient with non-resolving pyelonephritis and prolonged fever.

Discovery of a small-molecule inhibitor of KSHV lytic replication from the MMV pandemic response box.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent for primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD) and Kaposi's sarcoma (KS). KSHV is one of the oncoviruses that contribute to 1.5 million new infection-related cancer cases annually. Currently, there are no targeted therapies for KSHV-associated diseases. Through the development of a medium-throughput phenotype-based ELISA screening platform based on KSHV ORF57 protein detection, we screened the Medicines for Malaria Venture (MMV) Pandemic Response Box for non-cytotoxic inhibitors of KSHV lytic replication. MMV1645152 was identified as a promising inhibitor of KSHV lytic replication, suppressing KSHV immediate-early and late lytic gene expression and blocking the production of infectious KSHV virion particles at non-cytotoxic concentrations in cell line models of KSHV infection with or without EBV coinfection. MMV1645152 is a promising hit compound for the development of future therapeutic agents against KSHV-associated malignancies.

Mini review advantages and limitations of lytic phages compared with chemical antibiotics to combat bacterial infections.

The overuse of antibiotics has caused the emergence of antibiotic-resistant strains, such as multidrug-resistant, extensively drug-resistant, and pandrug-resistant bacteria. The treatment of infections caused by such strains has become a formidable challenge. In the post-antibiotic era, phage therapy is an attractive solution for this problem and some successful phase 1 and 2 studies have demonstrated the efficacy and safety of phage therapy over the last decade. It is a form of evolutionary medicine, phages exhibit immunomodulatory and anti-inflammatory properties. However, phage therapy is limited by factors, such as the narrow spectrum of host strains, the special pharmacokinetics and pharmacodynamics in vivo, immune responses, and the development of phage resistance. The aim of this minireview was to compare the potencies of lytic phages and chemical antibiotics to treat bacterial infections. The advantages of phage therapy has fewer side effects, self-replication, evolution, bacterial biofilms eradication, immunomodulatory and anti-inflammatory properties compared with chemical antibiotics. Meanwhile, the disadvantages of phage therapy include the narrow spectrum of available host strains, the special pharmacokinetics and pharmacodynamics in vivo, immune responses, and phage resistance hurdles. Recently, some researchers continue to make efforts to overcome these limitations of phage therapy. Phage therapy will be a welcome addition to the gamut of options available for treating antibiotic-resistant bacterial infections. We focus on the advantages and limitations of phage therapy with the intention of exploiting the advantages and overcoming the limitations.

Hydatid cyst of the humerus presenting as a suspicious lesion: A rare case report and review of literature.

Hydatidosis is a parasitic disease caused by the tapeworm Echinococcus. Echinococcus Granulosus is the most common cause of hydatid disease in humans. Bone involvement is rare, accounting for only 0.9% to 2.5% of all cases. We report the case of an 8-year-old child admitted with right arm pain, revealing a hydatid cyst on the humerus. Lesion assessment revealed a hydatid cyst of the humerus with extension to the adjacent soft tissues. The surgical procedure involved the excision of the cyst along with drainage. In this case report, we review the epidemiological, clinical, and paraclinical aspects of the disease, as well as the treatment modalities. Bone hydatid disease is infiltrative, diffuse, slow, and progressive, making diagnosis late, and compromising the quality of treatment.

Lytic lesion of the mandible revealing a metastatic breast cancer.

INTRODUCTION AND IMPORTANCE: Breast cancer is the most common cancer in women and the second leading cause of cancer-related death. Breast cancer manifestations in the head and neck are relatively rare, have greater predilection for the jaws than for soft tissues. Metastasis in the oral cavity account for only 1 to 3 % of all oral malignant lesions. Regardless of the rare occurrence of metastatic lesions to the jaw, it should be taken into consideration in the individuals with a history of malignancy. CASE PRESENTATION: The article reports a rare case of metastatic lesion of breast cancer to unilateral mandibular ramus region. The 66-year-old female patient was complaining of pain and swelling in the right mandible angle. She was referred to our department by her oncologist with the differential diagnosis of osteonecrosis or metastasis. She had undergone radical mastectomy for invasive lobular carcinoma of the left breast without adjuvant treatment. Oral cavity examination did not reveal the existence of any ulcer or fistula. Based on the patient's medical history and paresthesia of the lower lip and chin, the metastatic disease was highly suspected. The patient was referred to her oncologist for chemotherapy treatment before any invasive surgical management. CLINICAL DISCUSSION: Breast cancer (BC) is the most common cancer affecting women globally. Bone is the most common site of metastasis in BC patients, with up to 75 % of stage IV BC patients developing skeletal metastasis. The frequent metastatic sites of bone are spine, ribs, sternum, femur, pelvis. Breast carcinoma metastasizes to the jaw bones are uncommon. CONCLUSION: The diagnosis of metastasis to the oral cavity is a significant challenge to the clinician due to the lack of pathognomonic signs and symptoms. The general dentist or dental specialist should maintain a high level of suspicion while dealing patients with a history of cancer.

Identification of Lytic Phages Against Multidrug-Resistant Klebsiella pneumoniae: Illuminating Hope on Antimicrobial-Resistance.

Background: Lytic phages have been considered as a solution to mitigate the emergence of multidrug-resistant bacteria. Nevertheless, finding phages capable of targeting a broad host-range remains a significant challenge. Materials and Methods: Our study introduces two lytic phages isolated from hospital effluent, which are active against extended-spectrum cephalosporin-resistant Klebsiella pneumoniae. Results: Overnight coculture with host, two purified phage lysates yielded around 3.0 × 107 PFU/mL with an average 0.8 ± 0.2 mm diameter of clear, round, and non-halo plaques in both instances. The genomes of iPHaGe-KPN-11i (177,603 bp, 273 coding sequences [CDS]) and iPHaGe-KPN-12i (178,179 bp, 275 CDS) belong to the Pseudotevenvirus genus. Both phages have at least 120 genes with known functions, including 1 endolysin and 2 tRNAs, and are capable of lysing at least 12 distinct bacterial species in vitro. Conclusions: Most phages are host-specific, whereas our phages can kill multiple bacterial species, enabling their potential use for a broad range of hosts.

Characterization and genomic analysis of a lytic Stenotrophomonas maltophilia short-tailed phage A1432 revealed a new genus of the family Mesyanzhinovviridae.

Stenotrophomonas maltophilia (S. maltophilia) is an emerging opportunistic pathogen that exhibits resistant to a majority of commonly used antibiotics. Phages have the potential to serve as an alternative treatment for S. maltophilia infections. In this study, a lytic phage, A1432, infecting S. maltophilia YCR3A-1, was isolated and characterized from a karst cave. Transmission electron microscopy revealed that phage A1432 possesses an icosahedral head and a shorter tail. Phage A1432 demonstrated a narrow host range, with an optimal multiplicity of infection of 0.1. The one-step growth curve indicated a latent time of 10 min, a lysis period of 90 min, a burst size of 43.2 plaque-forming units per cell. In vitro bacteriolytic activity test showed that phage A1432 was capable to inhibit the growth of S. maltophilia YCR3A-1 in an MOI-dependent manner after 2 h of co-culture. BLASTn analysis showed that phage A1432 genome shares the highest similarity (81.46%) with Xanthomonas phage Xoo-sp2 in the NCBI database, while the query coverage was only 37%. The phage contains double-stranded DNA with a genome length of 61,660 bp and a GC content of 61.92%. It is predicted to have 79 open reading frames and one tRNA, with no virulence or antibiotic resistance genes. Phylogenetic analysis using terminase large subunit and DNA polymerase indicated that phage A1432 clustered with members of the Bradleyvirinae subfamily but diverged into a distinct branch. Further phylogenetic comparison analysis using Average Nucleotide Identity, proteomic phylogenetic analysis, genomic network analysis confirmed that phage A1432 belongs to a novel genus within the Bradleyvirinae subfamily, Mesyanzhinovviridae family. Additionally, phylogenetic analysis of the so far isolated S. maltophilia phages revealed significant genetic diversity among these phages. The results of this research will contribute valuable information for further studies on their morphological and genetic diversity, will aid in elucidating the evolutionary mechanisms that give rise to them.

Soil Giant Phage: Genome and Biological Characteristics of Sinorhizobium Jumbo Phage.

This paper presents the first in-depth research on the biological and genomic properties of lytic rhizobiophage AP-J-162 isolated from the soils of the mountainous region of Dagestan (North Caucasus), which belongs to the centers of origin of cultivated plants, according to Vavilov N.I. The rhizobiophage host strains are nitrogen-fixing bacteria of the genus Sinorhizobium spp., symbionts of leguminous forage grasses. The phage particles have a myovirus virion structure. The genome of rhizobiophage AP-J-162 is double-stranded DNA of 471.5 kb in length; 711 ORFs are annotated and 41 types of tRNAs are detected. The closest phylogenetic relative of phage AP-J-162 is Agrobacterium phage Atu-ph07, but no rhizobiophages are known. The replicative machinery, capsid, and baseplate proteins of phage AP-J-162 are structurally similar to those of Escherichia phage T4, but there is no similarity between their tail protein subunits. Amino acid sequence analysis shows that 339 of the ORFs encode hypothetical or functionally relevant products, while the remaining 304 ORFs are unique. Additionally, 153 ORFs are similar to those of Atu_ph07, with one-third of the ORFs encoding different enzymes. The biological properties and genomic characteristics of phage AP-J-162 distinguish it as a unique model for exploring phage-microbe interactions with nitrogen-fixing symbiotic microorganisms.

Comparison of simultaneous saccharification and fermentation with LPMO-supported hybrid hydrolysis and fermentation.

Enzymatic saccharification is used to convert polysaccharides in lignocellulosic biomass to sugars which are then converted to ethanol or other bio-based fermentation products. The efficacy of commercial cellulase preparations can potentially increase if lytic polysaccharide monooxygenase (LPMO) is included. However, as LPMO requires both a reductant and an oxidant, such as molecular oxygen, a reevaluation of process configurations and conditions is warranted. Saccharification and fermentation of pretreated softwood was investigated in demonstration-scale experiments with 10 m3 bioreactors using an LPMO-containing cellulase preparation, a xylose-utilizing yeast, and either simultaneous saccharification and fermentation (SSF) or hybrid hydrolysis and fermentation (HHF) with a 24-hour or 48-hour initial phase and with 0.15 vvm aeration before addition of the yeast. The conditions used for HHF, especially with 48 h initial phase, resulted in better glucan conversion, but in poorer ethanol productivity and in poorer initial ethanol yield on consumed sugars than the SSF. In the SSF, hexose sugars such as glucose and mannose were consumed faster than xylose, but, in the end of the fermentation >90% of the xylose had been consumed. Chemical analysis of inhibitory pretreatment by-products indicated that the concentrations of heteroaromatic aldehydes (such as furfural), aromatic aldehydes, and an aromatic ketone decreased as a consequence of the aeration. This was attributed mainly to evaporation caused by the gas flow. The results indicate that further research is needed to fully exploit the advantages of LPMO without compromising fermentation conditions.

Novel lytic bacteriophage AhFM11 as an effective therapy against hypervirulent Aeromonas hydrophila.

Several farmed fish species, including carps, tilapia, salmon, and catfish, have experienced significant economic losses in aquaculture due to motile Aeromonas septicemia caused by Aeromonas hydrophila. In the present study, a novel lytic bacteriophage infecting hypervirulent Aeromonas hydrophila (vAh) was isolated and characterized. This is the first report of a phage against vAh. Phage AhFM11 demonstrated lytic activity against both vAh strains and the A. hydrophila reference strain ATCC 35654. The AhFM11 genome was sequenced and assembled, comprising 168,243 bp with an average G + C content of 41.5%. The genome did not harbor any antibiotic resistance genes. Genomic information along with transmission electron microscopy revealed that phage AhFM11 belongs to the Straboviridae family. Therapeutic application of monophage AhFM11 in fish showed 100% survival in injection, 95% in immersion and 93% in oral feeding of phage top-coated feed. Fish and chicken meat spiked with A. hydrophila and phage showed significant reduction of A. hydrophila. These findings support that phage AhFM11 can be used as a biocontrol agent against vAh as an alternative to antibiotics.

Conserved cysteine residues in Kaposi's sarcoma herpesvirus ORF34 are necessary for viral production and viral pre-initiation complex formation.

Kaposi's sarcoma herpesvirus (KSHV) ORF34 plays a significant role as a component of the viral pre-initiation complex (vPIC), which is indispensable for late gene expression across beta- and gammaherpesviruses. Although the key role of ORF34 within the vPIC and its function as a hub protein have been recognized, further clarification regarding its specific contribution to vPIC functionality and interactions with other components is required. This study employed a deep learning algorithm-assisted structural model of ORF34, revealing highly conserved amino acid residues across human beta- and gammaherpesviruses localized in structured domains. Thus, we engineered ORF34 alanine-scanning mutants by substituting conserved residues with alanine. These mutants were evaluated for their ability to interact with other vPIC factors and restore viral production in cells harboring the ORF34-deficient KSHV-BAC. Our experimental results highlight the crucial role of the four cysteine residues conserved in ORF34: a tetrahedral arrangement consisting of a pair of C-Xn-C consensus motifs. This suggests the potential incorporation of metal cations in interacting with ORF24 and ORF66 vPIC components, facilitating late gene transcription, and promoting overall virus production by capturing metal cations. In summary, our findings underline the essential role of conserved cysteines in KSHV ORF34 for effective vPIC assembly and viral replication, thereby enhancing our understanding of the complex interplay between the vPIC components. IMPORTANCE: The initiation of late gene transcription is universally conserved across the beta- and gammaherpesvirus families. This process employs a viral pre-initiation complex (vPIC), which is analogous to a cellular PIC. Although KSHV ORF34 is a critical factor for viral replication and is a component of the vPIC, the specifics of vPIC formation and the essential domains crucial for its function remain unclear. Structural predictions suggest that the four conserved cysteines (C170, C175, C256, and C259) form a tetrahedron that coordinates the metal cation. We investigated the role of these conserved amino acids in interactions with other vPIC components, late gene expression, and virus production to demonstrate for the first time that these cysteines are pivotal for such functions. This discovery not only deepens our comprehensive understanding of ORF34 and vPIC dynamics but also lays the groundwork for more detailed studies on herpesvirus replication mechanisms in future research.

Reductant-independent oxidative cleavage of cellulose by a novel marine fungal lytic polysaccharide monooxygenase.

Among the enzymes derived from fungus that act on polysaccharides, lytic polysaccharide monooxygenase (LPMOs) has emerged as a new member with complex reaction mechanisms and high efficiency in dealing with recalcitrant crystalline polysaccharides. This study reported the characteristics, structure, and biochemical properties of a novel LPMO from Talaromyces sedimenticola (namely MaLPMO9K) obtained from the Mariana Trench. MaLPMO9K was a multi-domain protein combined with main body and a carbohydrate-binding module. It was heterologously expressed in E. coli for analyzing peroxidase activity in reactions with the substrate 2,6-DMP, where H2O2 serves as a co-substrate. Optimal peroxidase activity for MaLPMO9K was observed at pH 8 and 25 °C, achieving the best Vmax value of 265.2 U·g-1. In addition, MaLPMO9K also demonstrated the ability to treat cellulose derivatives, and cellobiose substrates without the presence of reducing agents.

An approach for the intracellular delivery of IgG via enzymatic ligation with a cell-permeable attenuated cationic amphiphilic lytic peptide.

Achieving effective intracellular delivery of therapeutic molecules such as antibodies (IgG) is a challenge in biomedical research and pharmaceutical development. Conjugation of IgG with a cell-penetrating peptide is a rational approach. Here, not only the efficacy of the conjugates in internalizing into cells, but also the physicochemical property of the conjugates allowing their solubilized states in solution without forming aggregates are critical. In this study, we have shown that the first requirement can be addressed using a cell-permeable attenuated cationic amphiphilic lytic (CP-ACAL) peptide, L17ER4. The second requirement can be addressed by ligation of IgG to L17ER4 using sortase A, where the use of a linker of appropriate chain length is also important. For evaluation, the intracellular delivery efficacy was studied using conjugate structures with different orientations and conjugation modes of L17ER4 in ligation to a model protein, green fluorescent protein fused to a nuclear localization signal (NLS-EGFP). The effect of tetraarginine positioning in the L17ER4 sequence was also investigated. Following these studies, an optimized peptide sequence containing L17ER4 was ligated to an anti-green fluorescent protein (GFP) IgG bearing a sortase A recognition sequence. Treatment of the cells with the conjugate of anti-GFP IgG and L17ER4 resulted in a high efficiency of cytosolic translocation of the conjugate and the binding to the target protein in the cell without significant aggregate formation. The feasibility of the d-form of L17ER4 as a CP-ACAL was also confirmed.

Phenotypic characterization and genomic analysis of a Salmonella phage L223 for biocontrol of Salmonella spp. in poultry.

The escalating incidence of foodborne salmonellosis poses a significant global threat to food safety and public health. As antibiotic resistance in Salmonella continues to rise, there is growing interest in bacteriophages as potential alternatives. In this study, we isolated, characterized, and evaluated the biocontrol efficacy of lytic phage L223 in chicken meat. Phage L223 demonstrated robust stability across a broad range of temperatures (20-70 °C) and pH levels (2-11) and exhibited a restricted host range targeting Salmonella spp., notably Salmonella Typhimurium and Salmonella Enteritidis. Characterization of L223 revealed a short latent period of 30 min and a substantial burst size of 515 PFU/cell. Genomic analysis classified L223 within the Caudoviricetes class, Guernseyvirinae subfamily and Jerseyvirus genus, with a dsDNA genome size of 44,321 bp and 47.9% GC content, featuring 72 coding sequences devoid of antimicrobial resistance, virulence factors, toxins, and tRNA genes. Application of L223 significantly (p < 0.005) reduced Salmonella Typhimurium ATCC 14,028 counts by 1.24, 2.17, and 1.55 log CFU/piece after 2, 4, and 6 h of incubation, respectively, in experimentally contaminated chicken breast samples. These findings highlight the potential of Salmonella phage L223 as a promising biocontrol agent for mitigating Salmonella contamination in food products, emphasizing its relevance for enhancing food safety protocols.

Identification and characterization of a novel thermostable PL7 alginate lyase from a submarine volcanic metagenomic library.

Seaweed biomass is as an abundant and renewable source of complex polysaccharides, including alginate which has a variety of applications. A sustainable method for exploiting alginate towards the production of valuable oligosaccharides is through enzymatic processing, using alginate lyases. Industrial refinement methods demand robust enzymes. Metagenomic libraries from extreme environments are a new source of unique enzymes with great industrial potential. Herein we report the identification of a new thermostable alginate lyase with only 58 % identity to known sequences, identified by mining a metagenomic library obtained from the hydrothermal vents of the volcano Kolumbo in the Aegean Sea (Kolumbo Alginate Lyase, KAlLy). Sequence analysis and biochemical characterization of KAlLy showed that this new alginate lyase is a Polysaccharide Lyase of family 7 (PL7) enzyme with endo- and exo-action on alginate and poly-mannuronic acid, with high activity at 60°C (56 ± 8 U/mg) and high thermostability (half-life time of 30 h at 50°C). The response surface methodology analysis revealed that the reaction optimum conditions with poly-mannuronic acid as substrate are 44°C, pH of 5.5 with 440 mM NaCl. This novel alginate lyase is a valuable addition to the toolbox of alginate modifying enzymes, due to its diverse sequence and its good thermal stability.

Isolation and Characterization of Two Novel Genera of Jumbo Bacteriophages Infecting Xanthomonas vesicatoria Isolated from Agricultural Regions in Mexico.

Bacterial spot is a serious disease caused by several species of Xanthomonas affecting pepper and tomato production worldwide. Since the strategies employed for disease management have been inefficient and pose a threat for environmental and human health, the development of alternative methods is gaining relevance. The aim of this study is to isolate and characterize lytic phages against Xanthomonas pathogens. Here, we isolate two jumbo phages, named XaC1 and XbC2, from water obtained from agricultural irrigation channels by the enrichment technique using X. vesicatoria as a host. We determined that both phages were specific for inducing the lysis of X. vesicatoria strains, but not of other xanthomonads. The XaC1 and XbC2 phages showed a myovirus morphology and were classified as jumbo phages due to their genomes being larger than 200 kb. Phylogenetic and comparative analysis suggests that XaC1 and XbC2 represent both different and novel genera of phages, where XaC1 possesses a low similarity to other phage genomes reported before. Finally, XaC1 and XbC2 exhibited thermal stability up to 45 °C and pH stability from 5 to 9. All these results indicate that the isolated phages are promising candidates for the development of formulations against bacterial spot, although further characterization is required.

KDM5A/B contribute to HIV-1 latent infection and survival of HIV-1 infected cells.

Combinational antiretroviral therapy (cART) suppresses human immunodeficiency virus type 1 (HIV-1) viral replication and pathogenesis in acquired immunodeficiency syndrome (AIDS) patients. However, HIV-1 remains in the latent stage of infection by suppressing viral transcription, which hinders an HIV-1 cure. One approach for an HIV-1 cure is the "shock and kill" strategy. The strategy focuses on reactivating latent HIV-1, inducing the viral cytopathic effect and facilitating the immune clearance for the elimination of latent HIV-1 reservoirs. Here, we reported that the H3K4 trimethylation (H3K4me3)-specific demethylase KDM5A/B play a role in suppressing HIV-1 Tat/LTR-mediated viral transcription in HIV-1 latent cells. Furthermore, we evaluated the potential of KDM5-specific inhibitor JQKD82 as an HIV-1 "shock and kill" agent. Our results showed that JQKD82 increases the H3K4me3 level at HIV-1 5' LTR promoter regions, HIV-1 reactivation, and the cytopathic effects in an HIV-1-latent T cell model. In addition, we identified that the combination of JQKD82 and AZD5582, a non-canonical NF-κB activator, generates a synergistic impact on inducing HIV-1 lytic reactivation and cell death in the T cell. The latency-reversing potency of the JQKD82 and AZD5582 pair was also confirmed in peripheral blood mononuclear cells (PBMCs) isolated from HIV-1 aviremic patients and in an HIV-1 latent monocyte. In latently infected microglia (HC69) of the brain, either deletion or inhibition of KDM5A/B results in a reversal of the HIV-1 latency. Overall, we concluded that KDM5A/B function as a host repressor of the HIV-1 lytic reactivation and thus promote the latency and the survival of HIV-1 infected reservoirs.

Random forest machine-learning algorithm classifies white- and brown-rot fungi according to the number of the genes encoding Carbohydrate-Active enZyme families.

Wood-rotting fungi play an important role in the global carbon cycle because they are the only known organisms that digest wood, the largest carbon stock in nature. In the present study, we used linear discriminant analysis and random forest (RF) machine learning algorithms to predict white- or brown-rot decay modes from the numbers of genes encoding Carbohydrate-Active enZymes with over 98% accuracy. Unlike other algorithms, RF identified specific genes involved in cellulose and lignin degradation, including auxiliary activities (AAs) family 9 lytic polysaccharide monooxygenases, glycoside hydrolase family 7 cellobiohydrolases, and AA family 2 peroxidases, as critical factors. This study sheds light on the complex interplay between genetic information and decay modes and underscores the potential of RF for comparative genomics studies of wood-rotting fungi. IMPORTANCE: Wood-rotting fungi are categorized as either white- or brown-rot modes based on the coloration of decomposed wood. The process of classification can be influenced by human biases. The random forest machine learning algorithm effectively distinguishes between white- and brown-rot fungi based on the presence of Carbohydrate-Active enZyme genes. These findings not only aid in the classification of wood-rotting fungi but also facilitate the identification of the enzymes responsible for degrading woody biomass.