host-pathogen interaction

Intracellular bacterial infections are challenging to treat because of the bacterial ability to resist antibiotics and evade the host’s immune system. These bacteria (whether facultative or obligate) cause infections of varying severity that necessitate timely intervention. According to a study, around ~1 billion people are at risk of being infected by intracellular bacteria.1 Accordingly, this review aimed to explore some examples of such bacteria, infectious diseases, challenges in their treatment, and the existing therapeutic options while exploring cutting-edge, innovative methods for treatment as well as their limitations and potentials. Thus, the study focused on reviewing many possible therapeutic options, such as antibiotics, nanotechnology-based therapeutics, host-directed therapies (HDTs), small inhibitor molecules, antimicrobial peptides (AMPs), phage therapies, and clustered regularly interspaced palindromic repeat-CRISPR-associated (CRISPR-Cas) systems, with their pros and cons. A thorough review of available case studies and clinical trials was conducted as well. Precise and cost-effective diagnostic approaches and targeted treatments showing positive results in clinical trials/case studies will enhance therapeutic efficacy and are expected to offer explanations for tenacious bacterial infections. The findings of this study revealed that the use of antibiotics is foundational. However, due to antibiotic resistance, a call for all other supporting approaches (discussed in this article) that provide new avenues is crucial. Each strategy necessitates optimization in cost, immune compatibility, and delivery methods. However, combined approaches, such as phage therapy with CRISPR-Cas systems, may offer better solutions to the presented challenges. Upcoming studies can combine modern biological methods and implement multidisciplinary strategies that include biotechnology, microbiology, and computational sciences to increase quick monitoring.  

Cellular stress, induced by diverse factors including viral infection, reactive oxygen species (ROS), hypoxia, and toxin exposure, disrupts normal cellular function. The endoplasmic reticulum (ER) is pivotal in managing cellular stress, notably through the unfolded protein response (UPR) and ER-associated degradation (ERAD) pathways. This intricate process involves a complex interplay of transcription factors and signaling molecules. During viral infection, cells activate a multifaceted antiviral response, which is specifically modulated by both the virus type and the molecular mechanisms of the host's immune system. For instance, certain viruses like Japanese encephalitis virus (JEV) exploit multiple cellular pathways for replication and propagation. Viral infection can significantly impact cellular processes like autophagy and apoptosis, either promoting or suppressing these pathways. Thus, the cellular response to viral infection represents a dynamic interplay that can either benefit the host or be exploited by the virus for its propagation. For instance, viruses within the Flaviviridae family often preserve host cell viability during early infection to enhance replication, subsequently triggering apoptosis or other cell death mechanisms to facilitate viral dissemination. This review explores the diverse responses of infected cells to various viruses, highlighting the complex molecular strategies employed by both host and pathogen.

Multiple outbreaks over two decades and a high mortality rate have emphasized the Nipah virus (NiV) as a priority research area. The study focuses on identifying the mutational landscape in sequences from NiV human isolates from different geographical regions.

Thirty-seven NiV genomes of human samples from Malaysia, Bangladesh, and India were subject- ed to phylogeny and metagenomic analysis to decipher the genome variability using MEGA11 software and the meta-CATS web server. Using the Single-Likelihood Ancestor Counting method, the synonymous and nonsynonymous mutations among NiV genes were identified. Further, the nonsynonymous variations were used to identify mutations in all the NiV proteins.

The NiV isolates were categorized into NiV-M, NiV-B, and NiV-I clades based on phylogenetic analysis. Metag- enomic analysis revealed 1636 variations in the noncoding and coding regions of the genomes of the three clades of NiV. Further analysis of nonsynonymous mutations showed the phosphoprotein to be highly mutating, whereas the matrix protein was stable.

Deciphering the mutation pattern using a comparative genomics approach for human isolates provided valuable insight into the stability of NiV proteins which can be further used for understanding variations in host-pathogen interaction and developing effective therapeutic measures.