Therapeutic options for many infections are extremely limited and at crisis point. We run the risk of entering a second pre-antibiotic era. There had been no miracle drug for the patients infected by resistant microbial pathogens. Most of the very few new drugs under development have problems with their toxicity, or pharmacokinetics and pharmacodynamics. We are already decades behind in the discovery, characterization and development of new antimicrobials. In that scenario, we could not imagine surviving without newer and effective antimicrobial agents. Bacteria have been the champions of evolution and are still evolving continuously, where they pose serious challenges for humans. Along with the crisis of evolving resistance, the condition is made worst by the meager drug pipeline for new antimicrobials. Despite ongoing efforts only 2 new antibiotics (Telavancin in 2009 and Ceftaroline fosamil in 2010) have been approved since 2009 pipeline status report of Infectious Disease Society of America (IDSA). Recent approval of new combination based antiviral drugs such as Stribild (combination of four drugs for HIV treatment) and Menhibrix (combination vaccine to prevent meningococcal disease and Haemophilus influenzae type b in children) proves that combination therapy is still the most promising approach to combat the ever evolving pathogens. Combination therapy involves the drug repurposing and regrouping of the existing antimicrobial agents to provide a synergistic approach for management of infectious diseases. This review article is an effort to highlight the challenges in new drug development and potential of combination drug therapy to deal with them.

<P>Background: Protein-Protein interaction (PPI) network analysis of virulence proteins of Aspergillus fumigatus is a prevailing strategy to understand the mechanism behind the virulence of A. fumigatus. The identification of major hub proteins and targeting the hub protein as a new antifungal drug target will help in treating the invasive aspergillosis. </P><P> Materials & Method: In the present study, the PPI network of 96 virulence (drug target) proteins of A. fumigatus were investigated which resulted in 103 nodes and 430 edges. Topological enrichment analysis of the PPI network was also carried out by using STRING database and Network analyzer a cytoscape plugin app. The key enriched KEGG pathway and protein domains were analyzed by STRING. Conclusion: Manual curation of PPI data identified three proteins (PyrABCN-43, AroM-34, and Glt1- 34) of A. fumigatus possessing the highest interacting partners. Top 10% hub proteins were also identified from the network using cytohubba on the basis of seven algorithms, i.e. betweenness, radiality, closeness, degree, bottleneck, MCC and EPC. Homology model and the active pocket of top three hub proteins were also predicted.</P>

Results from this study recommend that plant rhizosphere remains a rich hotspot for delivering a novel antifungal compounds.

Prevalence of pathogenic microorganisms in the rhizosphere causing infectious diseases in plants and humans has increased considerably due to a high content of nutrients. Such pathogenic infections are of huge concern in agriculture, health care, and medical arenas. Rhizosphere microbiome is a “microbial hotspot,” not only for pathogenic microorganism but also for unlimited beneficial microorganisms. Therefore, this microbiome has immense potential in the shaping of earth from natural vegetation to the intense agricultural production to human health. Rhizosphere microorganism from unexplored habitats is a promising approach to overcome the escalating threat of such pathogenic infections. Hence, efforts are being made to isolate more and more rhizobacteria that are beneficial for better plant productivity and for treating human diseases. Thus, present review highlights and discusses the available literature on beneficial/pathogenic microorganisms belonging to rhizosphere and their impact on plants and human diseases. Furthermore, it sheds light on how this novel knowledge helps in deriving maximum benefits out of this naturally occurring population for the betterment of plant and human health.