Roshan Kumar

Microbial communities produce metabolites, regulate inflammation, alter mucosal integrity, metabolize dietary and pharmacological compounds, and influence whether a patient tolerates or responds to chemotherapy, radiotherapy, immunotherapy, or surgery. High discrepancies in cancer incidence, progression, and outcomes across populations further highlight the importance of integrating microbial, biological, and socioeconomic factors into cancer research.The idea of this research topic, "Unlocking the Potential of the Microbiome in Cancer Therapy," was to elucidate the multifaceted roles of the microbiome in cancer therapy. Our goal was to deepen the understanding of how microbiome variations influence individual responses to cancer treatments and to investigate how microbial communities can be intentionally altered to enhance therapeutic outcomes. We were particularly interested in how microbial metabolites and immune system interactions can be harnessed to develop novel, more effective

The global prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has reached alarming levels, affecting nearly one-third of the world's population. This review analyzes current evidence on the intricate relationships between MASLD, insulin resistance, and type 2 diabetes mellitus (T2DM), with particular emphasis on gut microbiome interactions. As MASLD progresses from simple steatosis to Metabolic Dysfunction-Associated Steatohepatitis (MASH), it can lead to severe complications including fibrosis, cirrhosis, and hepatocellular carcinoma. The pathogenesis of MASLD is multifactorial, involving hepatic lipid accumulation, oxidative stress, inflammation, and dysregulation of the gut-liver axis. Insulin resistance is a central driver of disease progression, closely linked to obesity and metabolic syndrome. Recent research highlights how gut microbiome dysbiosis exacerbates MASLD through mechanisms such as increased intestinal permeability, systemic inflammation, and altered metabolic signaling. Identification of microbial signatures offers promise for novel diagnostic and therapeutic strategies. By integrating metabolic, inflammatory, and microbial perspectives, this review provides a comprehensive overview of MASLD pathogenesis and its association with obesity, insulin resistance, and T2DM.

Since December 2019, the world has witnessed a massive outbreak of a novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which prompted cross-national collaboration to establish essential diagnostics, effective treatment protocols, and most importantly the design and development of suitable COVID-19 vaccine candidates. This effort has been fueled by collaborations among academic researchers, funding agencies, companies, and regulatory authorities. As a result, more than 242 vaccine candidates are currently under clinical trial, and nearly 50 vaccines have been approved in different countries. In this study, we conduct a comprehensive review of 11 vaccine candidates that have been granted Emergency Use Listing (EUL) by the World Health Organization (WHO). Our review summarizes the mode of synthesis, mechanism of action, approval authority, target age group, efficacy, merits, and gaps of these vaccine candidates. Additionally, we provide comparative attributes of these vaccine candidates to enhance understanding of safety and well-being.

While the world is still recovering from the Covid-19 pandemic, monkeypox virus (MPXV) awaits to cause another global outbreak as a challenge to all of mankind. However, the Covid-19 pandemic has taught us a lesson to speed up the pace of viral genomic research for the implementation of preventive and treatment strategies. One of the important aspects of MPXV that needs immediate insight is its evolutionary lineage based on genomic studies. Utilizing high-quality isolates from the GISAID (Global Initiative on Sharing All Influenza Data) database, primarily sourced from Europe and North America, we employed a SNP-based whole-genome phylogeny method and identified four major clusters among 628 MPXV isolates. Our findings indicate a distinct evolutionary lineage for the first MPXV isolate, and a complex epidemiology and evolution of MPXV strains across various countries. Further analysis of the host–pathogen interaction network revealed key viral proteins, such as E3, SPI-2, K7 and CrmB, that play a significant role in regulating the network and inhibiting the host’s cellular innate immune system. Our structural analysis of proteins E3 and CrmB revealed potential disruption of stability due to certain mutations. While this study identified a large number of mutations within the new outbreak clade, it also reflected that we need to move fast with the genomic analysis of newly detected strains from around the world to develop better prevention and treatment methods.

The residue level of hexachlorocyclohexane (HCH) at contaminated dumpsites and nearby or related sites were studied. Water samples and sediments were collected from different HCH contaminated sites for residue analysis. These different sites include solexa data of dumpsite, Ummari, Lucknow (U.P.) (SolexaDS), dumpsite (DS) and two samples at the pond sediments near the pesticide industry, Chinhat, Lucknow (U.P.) (PS1 and PS2). 1km and 5km away from the DS i.e., 1km and 5km respectively were also included in the study. There was a correlation of HCH residue concentration at different sites with LinA and LinB protein distribution. Further, to investigate prevalence of LinA and LinB protein sequences in the metagenomic data sets of sites with different HCH gradients, a gene-centric approach was used. The study showed that in HCH stressed niches, LinA and LinB sequences from the metagenomes were found to cluster, thereby providing evidence in support of the proposed evolution of these proteins in the HCH contaminated environment.

Editorial: Multi-omics profiling of unique niches to reveal the microbial and metabolite composition

While the world is still managing to recover from Covid-19 pandemic, Monkeypox awaits to bring in another global outbreak as a challenge to the entire mankind. However, Covid-19 pandemic have taught us lessons to move fast in viral genomic research to implement prevention and treatment strategies. One of the important aspects in Monkeypox virus should be immediately taken up is to gather insights of its evolutionary lineage based on the genomic studies. We have thus analysed the genome sequences of reported isolates of Monkeypox in the present study through phylogenomics. Host-pathogen interactions, mutation prevalence and evolutionary dynamics of this virus were investigated for all the documented isolates. Phylogenetic exploration revealed the clustering of strain Israel 2018 (MN 648051.1) from Clade I with the four isolates reported from the recent outbreak. An in-depth scrutiny of the host-pathogen interactome identified protein E3, serine protease inhibitor-2 (SPI-2), protein K7, and cytokine response-modifying protein B (CrmB) as the major regulatory hubs. Among these, the CrmB protein (dN/dS ≈ 1.61) was detected to be operating through positive selection. It possibly attests a selective advantage with the monkeypox virus in protecting the infected cells from antiviral responses elicited by the host. Studies also revealed that CrmB protein exhibited several mutations, the majority of which were destabilizing (ΔΔG >0). While this study identified a large number of mutations within the newly outbreak clade, it also reflected that we need to move fast with the genomic analysis of the newly detected strains from around the world to develop better prevention and treatment methods

Among more than twenty species belonging to the class Mollecutes, Mycoplasma bovis is the most common cause of bovine mycoplasmosis in North America and Europe. Bovine mycoplasmosis causes significant economic loss in the cattle industry. The number of M. bovis positive herds recently has increased in North America and Europe. Since antibiotic treatment is ineffective and no efficient vaccine is available, M. bovis induced mycoplasmosis is primarily controlled by herd management measures such as the restriction of moving infected animals out of the herds and culling of infected or shedders of M. bovis. To better understand the population structure and genomic factors that may contribute to its transmission, we sequenced 147 M. bovis strains isolated from four different countries viz. USA (n = 121), Canada (n = 22), Israel (n = 3) and Lithuania (n = 1). All except two of the isolates (KRB1 and KRB8) were isolated from two host types i.e., bovine (n = 75) and bison (n = 70). We performed a large-scale comparative analysis of M. bovis genomes by integrating 103 publicly available genomes and our dataset (250 total genomes). Whole genome single nucleotide polymorphism (SNP) based phylogeny using M.agalactiae as an outgroup revealed that M. bovis population structure is composed of five different clades. USA isolates showed a high degree of genomic divergence in comparison to the Australian isolates. Based on host of origin, all the isolates in clade IV was of bovine origin, whereas majority of the isolates in clades III and V was of bison origin. Our comparative genome analysis also revealed that M. bovis has an open pangenome with a large breadth of unexplored diversity of genes. The function based analysis of autogenous vaccine candidates (n = 10) included in this study revealed that their functional diversity does not span the genomic diversity observed in all five clades identified in this study. Our study also found that M. bovis genome harbors a large number of IS elements and their number increases significantly (p = 7.8 × 10⁻⁶) as the genome size increases. Collectively, the genome data and the whole genome-based population analysis in this study may help to develop better understanding of M. bovis induced mycoplasmosis in cattle.

The genus Parapedobacter was established to describe a novel genus within the family Sphingobacteriaceae and derives its name from Pedobacter, with which it is shown to be evolutionarily related. Despite this, Parapedobacter and Pedobacter do not share very high 16S rRNA gene sequence similarities. Therefore, we hypothesized whether these substantial differences at the 16S rRNA gene level depict the true phylogeny or that these genomes have actually diverged. Thus, we performed genomic analysis of the four available genomes of Parapedobacter to better understand their phylogenomic position within family Sphingobacteriaceae. Our results demonstrated that Parapedobacter is more closely related to species of Olivibacter, as opposed to the genus Pedobacter. Further, we identified a significant class of enzymes called pectinases with potential industrial applications within the genomes of Parapedobacter luteus DSM 22899^T and Parapedobacter composti DSM 22900^T. These enzymes, specifically pectinesterases and pectate lyases, are presumed to have largely different catalytic activities based on very low sequence similarities to already known enzymes and thus may be exploited for industrial applications. We also determined the complete Bacteroides aerotolerance (Bat) operon (batA, batB, batC, batD, batE, hypothetical protein, moxR, and pa3071) within the genome of Parapedobacter indicus RK1^T. This expands the definition of genus Parapedobacter to containing members that are able to tolerate oxygen stress using encoded oxidative stress responsive systems. By conducting a signal propagation network analysis, we determined that BatD, BatE, and hypothetical proteins are the major controlling hubs that drive the expression of Bat operon. As a key metabolic difference, we also annotated the complete iol operon within the P. indicus RK1^T genome for utilization of all three stereoisomers of inositol, namely myo-inositol, scyllo-inositol, and 1D-chiro-inositol, which are abundant sources of organic phosphate found in soils. The results suggest that the genus Parapedobacter holds promising applications owing to its environmentally relevant genomic adaptations, which may be exploited in the future.

SARS-CoV-2 pandemic resulted in 92 million cases in a span of one year. The study focuses on understanding population specific variations attributing its high rate of infections in specific geographical regions particularly in USA. Rigorous phylogenomic network analysis of complete SARS-CoV-2 genomes (245) inferred five central clades named a (ancestral), b, c, d and e (subtype e1 & e2). The clade d & e2 were found exclusively comprising of USA. Clades were distinguished by 10 co-mutational combinations in Nsp3, ORF8, Nsp13, S, Nsp12, Nsp2 and Nsp6. Our analysis revealed that only 67.46% of SNP mutations were at amino acid level. T1103P mutation in Nsp3 was predicted to increase protein stability in 238 strains except 6 strains which were marked as ancestral type; whereas co-mutation (P409L & Y446C) in Nsp13 were found in 64 genomes from USA highlighting its 100% co-occurrence. Docking highlighted mutation (D614G) caused reduction in binding of Spike proteins with ACE2, but it also showed better interaction with TMPRSS2 receptor contributing to high transmissibility among USA strains. We also found host proteins, MYO5A, MYO5B, MYO5C had maximum interaction with viral proteins (N, S, M). Thus, blocking the internalization pathway by inhibiting MYO5 proteins which could be an effective target for COVID-19 treatment. The functional annotations of the HPI network were found to be closely associated with hypoxia and thrombotic conditions confirming the vulnerability and severity of infection. We also screened CpG islands in Nsp1 & N conferring ability of SARS-CoV-2 to enter and trigger ZAP activity inside host cell. Importance: In the current study we presented a global view of mutational pattern observed in SARS-CoV-2 virus transmission. This provided a who-infect-whom geographical model since the early pandemic. This is hitherto the most comprehensive comparative genomics analysis of full-length genomes for co-mutations at different geographical regions specially in USA strains. Compositional structural biology results suggested that mutations have balance of contrary forces effect on pathogenicity suggesting only few mutations to effective at translation level but not all. Novel HPI analysis and CpG predictions elucidates the proof of concept of hypoxia and thrombotic conditions in several patients. Thus, the current study focuses the understanding of population specific variations attributing high rate of SARS-CoV-2 infections in specific geographical regions which may eventually be vital for the most severely affected countries and regions for sharp development of custom-made vindication strategies.