Recent advances in microbial bioremediation have significantly enhanced the effectiveness of wastewater management, offering innovative and sustainable alternatives to conventional treatment methods. Microorganisms, including bacteria, fungi, and algae, are increasingly recognized for their remarkable ability to degrade, transform, and remove a broad spectrum of pollutants such as organic compounds, heavy metals, and emerging contaminants from wastewater. Cutting-edge research has led to the development of novel approaches such as bioaugmentation, bio-stimulation, and the use of genetically engineered microbes, which have improved the efficiency, specificity, and resilience of bioremediation processes. The application of microbial consortia and advanced bioreactor designs further optimizes pollutant removal under diverse environmental conditions. Additionally, omics technologies and systems biology are providing deeper insights into microbial community dynamics and metabolic pathways, enabling the fine-tuning of bioremediation strategies for targeted outcomes. Despite ongoing challenges related to scalability, environmental variability, and regulatory considerations, these advances are paving the way for more robust, cost-effective, and eco-friendly wastewater management solutions. Overall, the integration of innovative microbial technologies holds great promise for addressing global water quality challenges and promoting environmental sustainability.

Epitranscriptomic RNA modifications play a crucial role in the posttranscriptional regulation of gene expression. N⁶-methyladenosine (m⁶A) is the most prevalent internal modification of eukaryotic RNA and plays a pivotal role in RNA fate. RNA m⁶A modification is regulated by a group of cellular proteins, methyltransferases (writers) and demethylases (erasers), which add and remove the methyl group from adenosine, respectively. m⁶A modification is recognized by a group of cellular RNA-binding proteins (readers) that specifically bind to m⁶A-modified RNA, mediating effects on RNA stability, splicing, transport, and translation. The functional significance of m⁶A modification of viral and cellular RNA is an active area of virology research. In this review, we summarize and analyze the current literature on m⁶A modification of HIV-1 RNA, the multifaceted functions of m⁶A in regulating HIV-1 replication, and the role of viral RNA m⁶A modification in evading innate immune responses to infection. Furthermore, we briefly discuss the future directions and therapeutic implications of mechanistic studies of HIV-1 epitranscriptomic modifications.

RNA N6-methyladenosine (m6A) modification is important for regulating gene expression and innate immune responses to viral infection. HIV-1 in vitro infection induces a significant increase in m6A modification of cellular RNA; however, whether m6A levels of cellular RNA are affected by HIV-1 replication or by antiretroviral therapy (ART) in infected individuals remain unknown. Using dot blot or ELISA, we measured RNA m6A levels of peripheral blood monocytic cells (PBMCs) from healthy donors or HIV-1-infected individuals with or without ART. Using an RT-qPCR array, we quantified expression levels of 84 type-I interferon (IFN-I)-responsive genes in PBMCs from some individuals of these three groups. RNA m6A levels in PBMCs from HIV-1 viremic patients (n=10) were significantly higher (p ≤0.0001) compared to ART-treated individuals (n=22) or 1.5-fold higher compared to healthy donors (n=14). However, the increase in RNA m6A levels did not correlate with changes in the expression of ten m6A-regulatory genes. We found significant upregulation or downregulation in the expression of several IFN-I-responsive genes from HIV-1 viremic patients (n=4) or ART-treated patients (n=6) compared to healthy donors (n=5). Our results suggest that post-transcriptional m6A modification may contribute to the regulation of IFN-I-responsive gene expression during HIV-1 infection and ART.

In the early phase of infection, the intramacrophage pathogen Leishmania donovani protects its niche with the help of the antiapoptotic protein myeloid cell leukemia-1 (MCL-1). Whether Leishmania could exploit MCL-1, an extremely labile protein, at the late phase is still unclear. A steady translational level of MCL-1 observed up to 48 h postinfection and increased caspase-3 activity in MCL-1–silenced infected macrophages documented its importance in the late hours of infection. The transcript level of MCL-1 showed a sharp decline at 6 h postinfection, and persistent MCL-1 expression in cyclohexamide-treated cells negates the possibility of de novo protein synthesis, thereby suggesting infection-induced stability. Increased ubiquitination, a prerequisite for proteasomal degradation of MCL-1, was also found to be absent in the late hours of infection. Lack of interaction with its specific E3 ubiquitin ligase MULE (MCL-1 ubiquitin ligase E3) and specific deubiquitinase USP9X prompted us to search for blockade of the ubiquitin-binding site in MCL-1. To this end, TCTP (translationally controlled tumor protein), a well-known binding partner of MCL-1 and antiapoptotic regulator, was found to be strongly associated with MCL-1 during infection. Phosphorylation of TCTP, a requirement for MCL-1 binding, was also increased in infected macrophages. Knockdown of TCTP decreased MCL-1 expression and short hairpin RNA–mediated silencing of TCTP in an infected mouse model of visceral leishmaniasis showed decreased parasite burden and induction of liver cell apoptosis. Collectively, our investigation revealed a key mechanism of how L. donovani exploits TCTP to establish infection within the host. Key Points Leishmania induces host antiapoptotic proteins MCL-1 and TCTP to inhibit apoptosis. TCTP–MCL-1 interaction prevents ubiquitination-mediated degradation of labile MCL-1. TCTP silencing led to reduction of organ parasite burden in visceral leishmaniasis.

N ⁶ -methyladenosine (m ⁶ A) is a major epitranscriptomic modification that regulates RNA metabolism and affects the replication and latency reversal of human immunodeficiency virus type 1 (HIV-1) in cells. Methyltransferase-like 3 (METTL3) is the principal catalytic enzyme responsible for m ⁶ A deposition, and its pharmacological inhibition has emerged as a potential therapeutic strategy for cancer and viral infections. However, the relative potency of METTL3 inhibitors in reducing m ⁶ A levels and their effects on HIV-1 latency reversal remain undefined. Here, we compared three commercially available METTL3 inhibitors (STM2457, STM3006, and STC-15) to evaluate their ability to reduce RNA m ⁶ A levels, suppress HIV-1 latency reversal, and affect cell viability in latently infected J-Lat cells and primary CD4 ⁺ T cells. In J-Lat cells, STM3006 and STC-15 were more potent than STM2457 in reducing RNA m ⁶ A levels at 24 and 48 h post-treatment, as reflected by lower half-maximal inhibitory concentrations (IC ₅₀ ). However, STM3006 and STC-15 exhibited significant cytotoxicity at concentrations above 2 µM at 48 h post-treatment, whereas STM2457 displayed minimal toxicity across all tested doses. In primary CD4 ⁺ T cells from three healthy donors, all three inhibitors reduced RNA m ⁶ A levels except STC-15 treatment of one donor’s cells, while STM3006 induced significant cytotoxicity at 24 h post-treatment. Notably, reduced RNA m ⁶ A levels correlated with diminished HIV-1 latency reversal in both J-Lat cells and a primary central memory CD4 ⁺ T cell model. Together, these findings demonstrate differential potency and cytotoxicity among METTL3 inhibitors and support a critical role for m ⁶ A RNA modification in regulating HIV-1 latency reversal.