Revisiting the smart metallic nanomaterials: advances in nanotechnology-based antimicrobials.

Despite significant advancements in diagnostics and treatments over the years, the problem of antimicrobial drug resistance remains a pressing issue in public health. The reduced effectiveness of existing antimicrobial drugs has prompted efforts to seek alternative treatments for microbial pathogens or develop new drug candidates. Interestingly, nanomaterials are currently gaining global attention as a possible next-generation antibiotics. Nanotechnology holds significant importance, particularly when addressing infections caused by multi-drug-resistant organisms. Alternatively, these biomaterials can also be combined with antibiotics and other potent biomaterials, providing excellent synergistic effects. Over the past two decades, nanoparticles have gained significant attention among research communities. Despite the complexity of some of their synthesis strategies and chemistry, unrelenting efforts have been recorded in synthesizing potent and highly effective nanomaterials using different approaches. With the ongoing advancements in nanotechnology, integrating it into medical procedures presents novel approaches for improving the standard of patient healthcare. Although the field of nanotechnology offers promises, much remains to be learned to overcome the several inherent issues limiting their full translation to clinics. Here, we comprehensively discussed nanotechnology-based materials, focusing exclusively on metallic nanomaterials and highlighting the advances in their synthesis, chemistry, and mechanisms of action against bacterial pathogens. Importantly, we delve into the current challenges and prospects associated with the technology.

Vaccine development for bacterial pathogens: Advances, challenges and prospects.

The advent and use of antimicrobials have played a key role in treating potentially life-threatening infectious diseases, improving health, and saving the lives of millions of people worldwide. However, the emergence of multidrug resistant (MDR) pathogens has been a significant health challenge that has compromised the ability to prevent and treat a wide range of infectious diseases that were once treatable. Vaccines offer potential as a promising alternative to fight against antimicrobial resistance (AMR) infectious diseases. Vaccine technologies include reverse vaccinology, structural biology methods, nucleic acid (DNA and mRNA) vaccines, generalised modules for membrane antigens, bioconjugates/glycoconjugates, nanomaterials and several other emerging technological advances that are offering a potential breakthrough in the development of efficient vaccines against pathogens. This review covers the opportunities and advancements in vaccine discovery and development targeting bacterial pathogens. We reflect on the impact of the already-developed vaccines targeting bacterial pathogens and the potential of those currently under different stages of preclinical and clinical trials. More importantly, we critically and comprehensively analyse the challenges while highlighting the key indices for future vaccine prospects. Finally, the issues and concerns of AMR for low-income countries (sub-Saharan Africa) and the challenges with vaccine integration, discovery and development in this region are critically evaluated.

Antimicrobial Peptides Therapy: An Emerging Alternative for Treating Drug-Resistant Bacteria.

Microbial resistance to antibiotics is an ancient and dynamic issue that has brought a situation reminiscent of the pre-antibiotic era to the limelight. Currently, antibiotic resistance and the associated infections are widespread and pose significant global health and economic burden. Thus, the misuse of antibiotics, which has increased resistance, has necessitated the search for alternative therapeutic agents for combating resistant pathogens. Antimicrobial peptides (AMPs) hold promise as a viable therapeutic approach against drug-resistant pathogens. AMPs are oligopeptides with low molecular weight. They have broad-spectrum antimicrobial activities against pathogenic microorganisms. AMPs are nonspecific and target components of microbes that facilitate immune response by acting as the first-line defense mechanisms against invading pathogenic microbes. The diversity and potency of AMPs make them good candidates for alternative use. They could be used alone or in combination with several other biomaterials for improved therapeutic activity. They can also be employed in vaccine production targeting drug-resistant pathogens. This review covers the opportunities and advances in AMP discovery and development targeting antimicrobial resistance (AMR) bacteria. Briefly, it presents an overview of the global burden of the antimicrobial resistance crisis, portraying the global magnitude, challenges, and consequences. After that, it critically and comprehensively evaluates the potential roles of AMPs in addressing the AMR crisis, highlighting the major potentials and prospects.

The resurgence of phage-based therapy in the era of increasing antibiotic resistance: From research progress to challenges and prospects.

Phage therapy was implemented almost a century ago but was subsequently abandoned when antibiotics emerged. However, the rapid emergence of drug-resistant, which has brought to the limelight situation reminiscent of the pre-antibiotic era, coupled with the unavailability of new drugs, has triggered the quest for an alternative therapeutic approach, and this has led to the rebirth of phage-derived therapy. Phages are viruses that infect and replicate in bacterial cells. Phage therapy, especially phage-derived proteins, is being given considerable attention among scientists as an antimicrobial agent. They are used alone or in combination with other biomaterials for improved biological activity. Over the years, much has been learned about the genetics and diversity of bacteriophages. Phage cocktails are currently being exploited for treating several infectious diseases as preliminary studies involving animal models and clinical trials show promising therapeutic efficacy. However, despite its numerous advantages, this approach has several challenges and unaddressed limitations. Addressing these issues requires lots of creativity and innovative ideas from interdisciplinary fields. However, with all available indications, phage therapy could hold the solution in this era of increasing antibiotic resistance. This review discussed the potential use of phages and phage-derived proteins in treating drug-resistant bacterial infections. Finally, we highlight the progress, challenges, and knowledge gaps and evaluate key questions requiring prompt attention for the full clinical application of phage therapy.

Genome plasticity in Candida albicans: A cutting-edge strategy for evolution, adaptation, and survival.

Candida albicans is the most implicated fungal species that grows as a commensal or opportunistic pathogen in the human host. It is associated with many life-threatening infections, especially in immunocompromised persons. The genome of Candida albicans is very flexible and can withstand a wide assortment of variations in a continuously changing environment. Thus, genome plasticity is central to its adaptation and has long been of considerable interest. C. albicans has a diploid heterozygous genome that is highly dynamic and can display variation from small to large scale chromosomal rearrangement and aneuploidy, which have implications in drug resistance, virulence, and pathogenicity. This review presents an up-to-date overview of recent genomic studies involving C. albicans. It discusses the accumulating evidence that shows how mitotic recombination events, ploidy dynamics, aneuploidy, and loss of heterozygosity (LOH) influence evolution, adaptation, and survival in C. albicans. Understanding the factors that affect the genome is crucial for a proper understanding of species and rapid development and adjustment of therapeutic strategies to mitigate their spread.

Helicobacter pylori: an up-to-date overview on the virulence and pathogenesis mechanisms.

Helicobacter pylori is an organism associated with ulcer disease and gastric cancer. The latter is one of the most prevalent malignancies and currently the fourth major cause of cancer-related deaths globally. The pathogen infects about 50% of the world population, and currently, no treatment ensures its total elimination. There has been an increase in our understanding of the pathophysiology and pathogenesis mechanisms of H. pylori over the years. H. pylori can induce several genetic alterations, express numerous virulence factors, and trigger diverse adaptive mechanisms during its adherence and colonization. For successful colonization and infection establishment, several effector proteins/toxins are released by the organism. Evidence is also available reporting spiral to coccoid transition as a unique tactic H. pylori uses to survive in the host's gastrointestinal tract (GIT). Thus, the virulence and pathogenicity of H. pylori are under the control of complex interplay between the virulence factors, host, and environmental factors. Expounding the role of the various virulence factors in H. pylori pathogenesis and clinical outcomes is crucial for vaccine development and in providing and developing a more effective therapeutic intervention. Here we critically reflect on H. pylori infection and delineate what is currently known about the virulence and pathogenesis mechanisms of H. pylori.

Immunobiology and nanotherapeutics of severe acute respiratory syndrome 2 (SARS-CoV-2): a current update.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes the most significant global public health challenge in a century. It has reignited research interest in coronavirus. While little information is available, research is currently in progress to comprehensively understand the general biology and immune response mechanism against SARS-CoV-2. The spike proteins (S protein) of SARS-CoV-2 perform a crucial function in viral infection establishment. ACE2 and TMPRSS2 play a pivotal role in viral entry. Upon viral entry, the released pro-inflammatory proteins (cytokines and chemokines) cause the migration of the T cells, monocytes, and macrophages to the infection site. IFNϒ released by T cells initiates a loop of pro-inflammatory feedback. The inflammatory state may further enhance with an increase in immune dysfunction responsible for the infection's progression. A treatment approach that prevents ACE2-mediated viral entry and reduces inflammatory response is a crucial therapeutic intervention strategy, and nanomaterials and their conjugates are promising candidates. Nanoparticles can inhibit viral entry and replication. Nanomaterials have also found application in targeted drug delivery and also in developing a vaccine against SARS-CoV-2. Here, we briefly summarize the origin, transmission, and clinical features of SARS-CoV-2. We then discussed the immune response mechanisms of SARS-CoV-2. Finally, we further discussed nanotechnology's potentials as an intervention strategy against SARS-CoV-2 infection. All these understandings will be crucial in developing therapeutic strategies against SARS-CoV-2.

The use of nanoparticles as alternative therapeutic agents against Candida infections: an up-to-date overview and future perspectives.

Candida spp. are opportunistic fungi that can cause severe infections especially in immunocompromised patients. Candidiasis is currently the most frequent fungal disease affecting humans globally. This rise is attributed to the vast increase in resistance to antifungal agents. In recent years, the epidemiological and clinical relevance of fungal infections caused by Candida species have attracted a lot of interest with increasing reports of intrinsic and acquired resistance among Candida species. Thus, the formulation of novel, and efficient therapy for Candida infection persists as a critical challenge in modern medicine. The use of nanoparticle as a potential biomaterial to achieve this feat has gained global attention. Nanoparticles have shown promising antifungal activity, and thus, could be seen as the next generation antifungal agents. This review concisely discussed Candida infection with emphasis on anti-candida resistance mechanisms and the use of nanoparticles as potential therapeutic agents against Candida species. Moreover, the mechanisms of activity of nanoparticles against Candida species, recent findings on the anti-candida potentials of nanoparticles and future perspectives are also presented.

Mechanism of Candida pathogenesis: revisiting the vital drivers.

Candida is the most implicated fungal pathogen in the clinical setting. Several factors play important roles in the pathogenesis of Candida spp. Multiple transcriptional circuits, morphological and phenotypic switching, biofilm formation, tissue damaging extracellular hydrolytic enzymes, metabolic flexibility, genome plasticity, adaptation to environmental pH fluctuation, robust nutrient acquisition system, adherence and invasions (mediated by adhesins and invasins), heat shock proteins (HSPs), cytolytic proteins, escape from phagocytosis, evasion from host immune system, synergistic coaggregation with resident microbiota, resistance to antifungal agents, and the ability to efficiently respond to multiple stresses are some of the major pathogenic determinants of Candida species. The existence of multiple connections, in addition to the interactions and associations among all of these factors, are distinctive features that play important roles in the establishment of Candida infections. This review describes all the underlying factors and mechanisms involved in Candida pathogenesis by evaluating pathogenic determinants of Candida species. It reinforces the already available pool of data on the pathogenesis of Candida species by providing a clear and simplified understanding of the most important factors implicated in the pathogenesis of Candida species. The Candida pathogenesis network, an illustration linking all the major determinants of Candida pathogenesis, is also presented. Taken together, they will further improve our current understanding of how these factors modulate virulence and consequent infection(s). Development of new antifungal drugs and better therapeutic approaches to candidiasis can be achieved in the near future with continuing progress in the understanding of the mechanisms of Candida pathogenesis.