Biology of infections

Globally, infectious diseases remain the leading cause of death, but these are particularly pernicious in developing economies of Asia, Africa, and Latin America. In these counties, the ever-increasing population density, migration of population to urban areas, and associated changes in environment and ecology provide fertile ground for the growth of infectious agents and emergence of the novel pathogens. Infectious diseases pose a serious challenge to the human health and economic well-being of the community worldwide. Vaccines, antivirals, novel antibiotics, and antibody-based strategies for passive immunization remain the most cost-effective means to combat infectious organisms. Knowledge of pathogen biology would help develop novel prophylactic and therapeutic measures for tackling infectious diseases. This special issue brings together a set of review articles focusing on the biology of some of the important viral, bacterial, and fungal pathogens. Provided below is a brief primer to these review articles.

A plethora of virus classes has been menacing humanity since time immemorial by causing varying degrees of respiratory distress. Bhattacharya et al. [REF in this issue] have outlined the interplay between the inflammation generated and the hypoxic response initiated by each of the commonly known respiratory viruses. A section specifically discusses the cytokine storm in COVID-19 patients and probable mechanisms underlying the most striking feature of the disease, i.e., silent hypoxia. They also review the inflammatory-hypoxic pathway that may be targeted therapeutically for a better prognosis.

Neutrophils are the primary responders of the innate immune system, acting as a double-edged sword in viral infections with both protective and detrimental roles. Viral infection may lead to the production of a different phenotype of neutrophils with modulated functions, shaping the outcome of the disease. In this context, the article by Rawat et al. [REF in this issue] highlights the recent findings of neutrophil extracellular traps (NETs) and their role in developing COVID-19 pathology.

Viruses modulate host cell organellar Ca²⁺ dynamics for their entry, replication, and exit, and hijack the cellular Ca²⁺ signalling for driving infection and pathogenesis. Viral proteins can directly interact and/or regulate the activity of host cell Ca²⁺ handling machinery. Saurav et al. [REF in this issue] present an overview of these emerging areas and dwell on how drugs targeting host cell Ca²⁺ handling proteins could be exploited for managing viral pathogenesis.

Despite the availability of vaccines in recent years, Japanese encephalitis continues to have a significant disease burden. Cellular stress responses-oxidative stress, ER stress, unfolded protein response, and autophagy, contribute significantly to the course of virus infection, immune response, and pathogenesis. These aspects, and how pharmacological modulation of these pathways holds potential for developing anti-viral and neuroprotective therapies, are reviewed in the article by Sharma et al. [REF in this issue]

Viruses with positive-sense RNA genomes are responsible for several diseases around the world. The virus-encoded RNA-dependent RNA polymerase (RdRP) enzyme is primarily responsible for the replication of the genome and represents an attractive target for antiviral development. Bhatia et al. [REF in this issue] describe different strategies employed by diverse small molecules to inhibit the RdRP enzyme and thus achieve the antiviral activity.

Pseudomonas aeruginosa is an opportunistic human pathogen that causes biofilm mediated chronic and hard to eradicate infections. Banerjee et al. [REF in this issue] have reviewed the structural studies on the enzymes that regulate the levels of a signalling molecule, c-di-GMP, essential for biofilm formation in bacterial cells. The review also describes the effector proteins that sense the perturbations in c-di-GMP levels to elicit a functional output. Uncovering the details of the regulation of this pathway is vital for understanding the behaviour of the pathogen and the characterization of novel targets for anti-biofilm interventions.

Non-typhoidal salmonellae (NTS) are the most frequent causative agents of localized gastroenteritis. In recent times, NTS have evolved into the systemic illness-causing variants capable of causing unexpected long-term disorders in the host. Rana et al. [REF in this issue] review the crucial molecular determinants and long-term side effects of the various NTS infections.

Protein synthesis is one of the most energy-consuming vital cellular processes that occur on the ribosome. Nearly 40% of known antibiotics, including anti-tuberculosis drugs, target the ribosome. Mycobacterium tuberculosis (Mtb) possesses several unique features in its protein synthesis machinery. The article by Kumar et al. [REF in this issue] highlights the mycobacteria-specific features of the translation machinery and discuss their potential for identifying novel anti-Mtb targets.

Decades of antibiotic misuse and overuse have led to a rise in antibiotic-resistant bacteria. New strategies are being vigorously explored to deal with this problem. An effective alternative to combat piliated pathogens has been to disrupt their pilus-mediated host attachment via various anti-adhesive therapies. The review by Sharma et al. [REF in this issue] describes the types of pili that have been characterized and the strategies that have emerged to prevent host colonization and infection by piliated pathogens.

Modifications of drug targets, impermeability of drugs across bacterial membranes, and inactivation of antibiotics are key mechanisms for the emergence of antimicrobial resistance by the bacteria. Therapeutic strategies targeting the bacterial membranes may not allow the bacteria to develop drug resistance. The review by Mehta et al. [REF in this issue] highlights the recent progress in engineering and development of membrane-targeting antimicrobials and discusses their potential for future antimicrobial therapeutics.

The emergence of human fungal pathogens and the increase in antifungal resistance pose a serious threat to human health. Post-transcriptional and translational mechanisms regulate the morphology and virulence of human fungal pathogens. The article by Rana et al. [REF in this issue] reviews these mechanisms, and how they could be exploited to develop antifungal agents.

RNAs have the capability of binding and modulating the activity of targets that are undruggable by either small molecules or monoclonal antibodies. Clinical translation of RNA-based drugs has been facilitated by advancements that address issues related to the stability, delivery, and immunogenicity of RNAs. Article by Pandey et al. [REF in this issue] highlights these aspects of RNA therapeutics and discusses how improvements in gene-editing approaches together with tissue-specific delivery methods will further revolutionize the field.

The diversity of the areas covered by the above articles gives an idea about the breadth and complexity of the field. Research on infectious diseases may be given greater emphasis for their potential ramifications. The ongoing COVID-19 pandemic has shown how infectious diseases could have a far-reaching effect on global health and the economy.

Declaration of competing interest

None declared.