Despite the widespread success of combination antiretroviral therapy (cART) in suppressing plasma viremia to undetectable levels, people living with HIV-1 (PLWH) continue to face a significantly elevated risk of chronic inflammation and Serious Non-AIDS Events (SNAEs). In this narrative review, we bridge the critical gap between molecular virology, immunometabolism, and clinical pathology by examining the complex interface of intrinsic immunity and viral persistence. We analyzed the evolutionary “arms race” between conserved host restriction factors, including TRIM5α, APOBEC3G, SAMHD1, BST-2, MX2, and SERINC, and the sophisticated viral evasion mechanisms that facilitate reservoir establishment. We further examined the role of bacterial translocation and gut barrier dysfunction in perpetuating systemic inflammation, emphasizing how HIV-1-mediated depletion of mucosal Th17 cells and disruption of tight junction proteins create a “leaky gut” that permits microbial product translocation despite suppressive therapy. Among viral proteins that may contribute to residual pathology during suppressive cART, we focused on the HIV-1 matrix protein p17, which has been proposed to function as a secreted “viral cytokine” from latent reservoirs, acting through CXCR1/CXCR2 receptors and the RACK1-JAK1-STAT1 pathway. Although primarily characterized in in vitro and ex vivo models, emerging data suggested that p17 may sustain systemic immune activation and metabolic reprogramming; however, its relative contribution compared with other viral proteins (Tat, Nef, gp120) in virologically suppressed patients remains to be fully delineated in human studies.Furthermore, we examined how HIV-1 hijacks cellular bioenergetics by shifting host cells from oxidative phosphorylation to aerobic glycolysis. We present an integrative model that connects restriction factor biology, p17-mediated chronic inflammation, immunometabolic dysregulation, and gut barrier dysfunction into a unified pathogenic framework, distinguishing established mechanisms from working hypotheses. Last, we assessed emerging therapeutic strategies, including CRISPR/Cas9-mediated enhancement of restriction factors, modulation of the mTOR pathway, and novel “Shock and Kill” approaches, stratified by development stage and demonstrated endpoints, offering potential pathways toward a functional cure.

Drug repositioning has emerged as a promising strategy for assessing its antimicrobial efficacy in treating infectious diseases. Seventy-five samples were collected and investigated for the presence of Pseudomonas aeruginosa. Antibiotic resistance, hemolytic activity, twitching motility, and biofilm formation were assessed. lasI and lasR genes were detected using conventional PCR. Minimum inhibitory concentrations of paroxetine, fluoxetine, and levofloxacin were determined by broth micro-dilution. The fractional inhibitory concentration index was calculated to assess the interaction between fluoxetine/levofloxacin and paroxetine/levofloxacin combinations. Half the MIC values of the drugs were selected for inhibitory effect assessment for virulence factors. Antibacterial and healing effects of fluoxetine were investigated on 30 male albino rats using a digital camera, bacterial count, and histological examination. Our 25 P. aeruginosa isolates were highly drug-resistant. 80%, 92%, and 80% of isolates were positive for twitching motility, hemolysis, and biofilm formation, respectively. 92% of isolates were positive for lasI gene and 96% for lasR gene. MICs of fluoxetine and paroxetine ranged from 32 to 512 µg/mL and MICs of levofloxacin ranged from 1 to 256 µg/mL. A synergistic outcome was observed in both combinations. Biofilm formation, twitching motility, and hemolysis were inhibited by paroxetine and fluoxetine in the majority of isolates. Fluoxetine/levofloxacin and paroxetine/levofloxacin combinations inhibited twitching motility, hemolysis, and biofilm formation in all isolates. Enhanced wound healing was observed in rats treated with fluoxetine and levofloxacin, with the fluoxetine/levofloxacin combination group demonstrating the most significant wound-healing effect. Bacterial count decreased in rats treated with levofloxacin, fluoxetine, and the levofloxacin/fluoxetine combination. Histological examination revealed higher wound healing in the levofloxacin-treated group than the fluoxetine group, and the combination treatment group displayed the fastest rate of wound healing. Paroxetine and fluoxetine showed considerable antibacterial inhibitory effects against multi-drug resistant P. aeruginosa isolates. Fluoxetine showed significant improvement in anti-inflammatory effects and wound healing. To the best of our knowledge, this is the first Egyptian study to investigate the repurposing of paroxetine and fluoxetine as antibacterial agents. Further studies are needed to investigate their applicability as antibacterial agents as single agents or in combination with other antibiotics.

Marine sponges are well-known for their production of bioactive compounds, many of which are synthesized by their associated symbiotic microorganisms. Among these, Actinomycetes are of particular interest due to their ability to produce secondary metabolites with antimicrobial and antitumor activities. We aimed to investigate the bacterial microbiome of tropical marine sponges, with an emphasis on the diversity and distribution of Actinomycetes, employing both culture-dependent and culture-independent approaches. Five sponge samples (PF01-PF05) were collected from Sichang Island, Chonburi Province, Thailand. The bacterial communities were analyzed using 16S rRNA gene sequencing and bioinformatics tools, revealing a significant microbial diversity dominated by Cyanobacteria, Actinomycetota, and Chloroflexi. Notably, PF01 (Penares nux) exhibited the highest microbial diversity, while PF05 (Cacospongia sp.) had the lowest. Actinomycetes, particularly the genus Micromonospora, were successfully isolated from all samples, with PF03 (Ircinia mutans) yielding the highest number of strains. Culture-independent analysis identified a greater proportion of unculturable Actinomycetes compared to those isolated through traditional methods, underscoring the limitations of culture-dependent techniques. This study enhances our understanding of sponge-associated microbial diversity and highlights the potential for isolating Actinomycetes from these sponges for novel drug discovery and other bioprospective applications.

ObjectiveAn increasing number of international researchers are focusing on the taxonomic composition of fecal microbiota and its correlation with disorders. Thousands of researchers compare conditionally healthy cohorts to those with specific diseases to identify potential markers. However, clinical application requires assessing the feasibility of synthesizing these findings and establishing reference intervals for normal gut flora, at least at higher taxonomic levels.DesignThis study involves a systematic review and meta-analysis of human gut microbiota research based on 16S rRNA gene next-generation sequencing (NGS). Relevant research was sourced following the PRISMA guidelines. Descriptive statistics, linear regression analysis by weighted least squares method, Mann-Whitney test, and Benjamini-Hochberg procedure adjustments were employed. The study has been registered with PROSPERO (CRD42023431467).ResultsOf the 4,346 studies initially identified, 86 publications involving 20,748 unique participants met the quality criteria and were included in the analysis of the impact of fecal sample preparation on taxonomic composition. The phylotype composition, in relation to preprocessing methods and cohort locations, are presented as relative abundances (%): Bacillota (median 49.5–59.6%), Bacteroidota (28.0–33.4%), Pseudomonadota (3.4–5.9%), Actinomycetota (2.3–3.7%), Verrucomicrobiota (0.5–1.0%), Fusobacteriota (maximum 4.6%), and Euryarchaeota (maximum 2.11%). The content of 27 key family-level representatives was also evaluated. The well-known hypothesis regarding the influence of the homogenization stage on taxonomic composition was examined using generalized results.ConclusionWhile supported by a strong theoretical basis and evidence from individual practical cases, none of the phyla showed a statistically significant association and consistent relationship with sample preparation or cohort location when generalizing across studies after the two exceptionally large cohorts exclusion, both originating from a single research group. These findings underscore the need for strict methodological standardization in microbiome studies. Key features of the 16S NGS process accounting for these results are outlined, along with proposed optimizations for microbiome research.

Antimicrobial resistance (AMR) is a significant global health challenge that threatens the effectiveness of antibiotics and other antimicrobial agents. Here, we examined the molecular mechanisms that contribute to bacterial resistance, including alterations at target sites, enzymatic inactivation, efflux pump overexpression, and biofilm formation. Key resistance determinants, such as blaCTX-M-15, blaNDM-1, mecA, and erm genes, mediate enzymatic degradation and target modification, thereby diminishing antibiotic potency. Clinically significant pathogens, including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecium, exemplify a broad spectrum of resistance and frequently acquire these traits through horizontal gene transfer (HGT), facilitated by plasmids, integrons, and transposons. The propensity for biofilm formation further augments bacterial persistence by impeding antimicrobial penetration and fostering intra-community genetic exchanges. The clinical ramifications of AMR are profound, contributing to elevated morbidity and mortality, extended hospitalization, and increased rates of therapeutic failure, all of which exert significant strain on the healthcare system. The economic consequences are equally severe, with escalating healthcare expenditures and substantial projected losses to the global gross domestic product (GDP). Addressing these challenges necessitates the adoption of advanced approaches, including genomic surveillance, antimicrobial stewardship, novel inhibitors targeting resistance pathways, immuno-antibiotics, and bacteriophage therapy. This review underscores the need to integrate molecular diagnostics and a One Health perspective to monitor and contain resistance across human, animal, and environmental reservoirs. A comprehensive understanding of the molecular and epidemiological aspects of AMR is essential for driving advancements in diagnostics, therapeutics, and policies, thereby ensuring global health protection.

<p>Colorectal cancer (CRC) continuously ranks as the third most common cause of cancer-related deaths worldwide. Based on anatomical classifications and clinical diagnoses, CRC is classified into right-sided, left-sided, and rectal CRC. Importantly, the three types of positional-specific CRC affect the prognosis outcomes, thus indicating that positional-specific treatments for CRC are required. Emerging evidence suggests that besides host genetic and epigenetic alterations, gut mucosal microbiota is linked to gut inflammation, CRC occurrence, and prognoses. However, gut mucosal microbiota associated with positional-specific CRC are poorly investigated. Here, we report the gut mucosal microbiota profiles associated with these three types of CRC. Our analysis showed that the unique composition and biodiversity of bacterial taxa are linked to positional-specific CRC. We found that a combination of bacterial taxa can serve as potential biomarkers to distinguish the three types of CRC. Further investigations of the physiological roles of bacteria associated with positional-specific CRC may help understand the mechanism of CRC progression in different anatomical locations under the impact of gut mucosal microbiota.</p>

The scab disease, caused by Elsinoe perseae, poses a significant risk to avocado (Persea americana) production in countries with warm and humid climates. Although the genome has been published, the precise virulence factors accountable for the pathogenicity of E. perseae have not yet been determined. The current study employed an in silico approach to identify and functionally characterize the secretory proteins of E. perseae. A total of 654 potential secretory proteins were identified, of which 190 were classified as carbohydrate-active enzymes (CAZymes), 49 as proteases, and 155 as potential effectors. A comparison to six other closely related species identified 40 species-specific putative effectors in E. perseae, indicating their specific involvement in the pathogenicity of E. perseae on avocado. The data presented in this study might be valuable for further research focused on understanding the molecular mechanisms that contribute to the pathogenicity of E. perseae on avocado.

Listeria monocytogenes is a concern in seafood and its food processing environment (FPE). Several outbreaks globally have been linked to various types of seafood. Genetic profiling of L. monocytogenes is valuable to track bacterial contamination throughout the FPE and in understanding persistence mechanisms, with limited studies from South Africa. Forty-six L. monocytogenes isolates from origins: Fish/seafood products (n = 32) (salmon, smoked trout, fresh hake, oysters), the FPE (n = 6), and clinical (n = 8) were included in this study. Lineage typing, antibiotic susceptibility testing, and screening for two genes (bcrABC and emrC) conferring sanitizer tolerance was conducted. The seafood and FPE isolates originated from seven different factories processing various seafood products with undetermined origin. All clinical isolates were categorized as lineage I, and seafood and FPE isolates were mostly categorized into lineage II (p < 0.01). Seafood and FPE isolates (53%) carried the bcrABC gene cassette and one fish isolate, the emrC gene. A subset, n = 24, was grouped into serotypes, sequence types (STs), and clonal complexes (CCs) with whole genome sequencing (WGS). Eight CCs and ten STs were identified. All clinical isolates belonged to serogroup 4b, hypervirulent CC1. CC121 was the most prevalent in isolates from food and the FPE. All isolates carried Listeria pathogenicity islands (LIPI) 1 and 2. LIPI-3 and LIPI-4 were found in certain isolates. We identified genetic determinants linked to enhanced survival in the FPE, including stress survival islets (SSI) and genes conferring tolerance to sanitizers. SSI-1 was found in 44% isolates from seafood and the FPE. SSI-2 was found in all the ST121 seafood isolates. Isolates (42%) harbored transposon Tn1688_qac (ermC), conferring tolerance to quaternary ammonium compounds. Five plasmids were identified in 13 isolates from seafood and the FPE. This is the first One Health study reporting on L. monocytogenes genetic diversity, virulence and resistance profiles from various types of seafood and its FPE in South Africa.

Actinomycetes are an attractive source of lignocellulose-degrading enzymes. The search for actinomycetes producing extremozyme cellulase using cheap lignocellulosic waste remains a priority goal of enzyme research. In this context, the extremophilic actinomycete NBRM9 showed promising cellulolytic activity in solid and liquid assays. This actinomycete was identified as Nocardiopsis synnemataformans based on its phenotypic characteristics alongside phylogenetic analyses of 16S rRNA gene sequencing (OQ380604.1). Using bean straw as the best agro-waste, the production of cellulase from this strain was statistically optimized using a response surface methodology, with the maximum activity (13.20 U/mL) achieved at an incubation temperature of 40 °C, a pH of 9, an incubation time of 7 days, and a 2% substrate concentration. The partially purified cellulase (PPC) showed promising activity and stability over a wide range of temperatures (20–90 °C), pH values (3–11), and NaCl concentrations (1–19%), with optimal activity at 50 °C, pH 9.0, and 10% salinity. Under these conditions, the enzyme retained >95% of its activity, thus indicating its extremozyme nature. The kinetics of cellulase showed that it has a Vmax of 20.19 ± 1.88 U/mL and a Km of 0.25 ± 0.07 mM. The immobilized PPC had a relative activity of 69.58 ± 0.13%. In the in vitro microtiter assay, the PPC was found to have a concentration-dependent anti-biofilm activity (up to 85.15 ± 1.60%). Additionally, the fermentative conversion of the hydrolyzed bean straw by Saccharomyces cerevisiae (KM504287.1) amounted to 65.80 ± 0.52% of the theoretical ethanol yield. Overall, for the first time, the present work reports the production of extremozymatic (thermo, alkali-, and halo-stable) cellulase from N. synnemataformans NBRM9. Therefore, this strain is recommended for use as a biotool in many lignocellulosic-based applications operating under harsh conditions.

&lt;p&gt;&lt;italic&gt;Phanerochaete chrysosporium&lt;/italic&gt; is considered the model fungus for white rot fungi. It is the first basidiomycete whose genome has been completely sequenced. Its importance lies in the fact that its enzymatic system comprises the major enzymes involved in lignin degradation. Lignin is a complex and highly recalcitrant compound that very few living organisms are capable of degrading naturally. On the other hand, the enzymes produced by &lt;italic&gt;P. chrysosporium&lt;/italic&gt; are also powerful agents for the mineralization into CO&lt;sub&gt;2&lt;/sub&gt; and H&lt;sub&gt;2&lt;/sub&gt;O of a wide range of aromatic compounds. However, these aromatic compounds are largely xenobiotic compounds with documented toxic effects on the environment and health. While the economic and environmental benefits of biodegradation with &lt;italic&gt;P. chrysosporium&lt;/italic&gt; are well established, a thorough understanding of &lt;italic&gt;P. chrysosporium&lt;/italic&gt; and its biodegradation processes is essential for successful biodegradation. Our aim of this critical literature review is to provide a concise and comprehensive insight of biodecomposition of organic substrate by &lt;italic&gt;P. chrysosporium&lt;/italic&gt;.&lt;/p&gt;