Phage therapeutics: from promises to practices and prospectives.

The rise in multi-drug resistant bacteria and the inability to develop novel antibacterial agents limits our arsenal against infectious diseases. Antibiotic resistance is a global issue requiring an immediate solution, including the development of new antibiotic molecules and other alternative modes of therapy. This article highlights the mechanism of bacteriophage treatment that makes it a real solution for multidrug-resistant infectious diseases. Several case reports identified phage therapy as a potential solution to the emerging challenge of multi-drug resistance. Bacteriophages, unlike antibiotics, have special features, such as host specificity and do not impact other commensals. A new outlook has also arisen with recent advancements in the understanding of phage immunobiology, where phages are repurposed against both bacterial and viral infections. Thus, the potential possibility of phages in COVID-19 patients with secondary bacterial infections has been briefly elucidated. However, significant obstacles that need to be addressed are to design better clinical studies that may contribute to the widespread use of bacteriophage therapy against multi-drug resistant pathogens. In conclusion, antibacterial agents can be used with bacteriophages, i.e. bacteriophage-antibiotic combination therapy, or they can be administered alone in cases when antibiotics are ineffective.Key points• AMR, a consequence of antibiotic generated menace globally, has led to the resurgence of phage therapy as an effective and sustainable solution without any side effects and high specificity against refractory MDR bacterial infections.• Bacteriophages have fewer adverse reactions and can thus be used as monotherapy as well as in conjunction with antibiotics.• In the context of the COVID-19 pandemic, phage therapy may be a viable option.

Molecular basis of the beta-lactamase protein using comparative modelling, drug screening and molecular dynamics studies to understand the resistance of ß-lactam antibiotics.

Beta-lactamase (ampC) in general causes the onset of antibiotic resistance in pathogenic bacteria against the ß-lactam antibiotics. Morganella morganii which belongs to the Proteae tribe of the Enterobacteriaceae family is a Gram-negative bacillus. Gram-negative bacteria are the key problematic agents among the human population in overexpressing resistance against ß-lactam antibiotics. These ß-lactam antibiotics being experimentally well studied still lack the key information and mechanism for their resistance. The structural information of the ampC protein is unknown and poorly studied; hence, it is the need of the hour to find effective inhibitors against it. In our study, the prediction of the three-dimensional structure of ampC protein from Morganella morganii was performed using a comparative modelling approach. The predicted structure was energetically stabilized and functional conformations were mapped through 100-ns molecular dynamics simulation runs. Also, Ramachandran plot shows the model to be stereo-chemically stable with most residues found under core allowed regions. Drug screening with several experimentally tested inhibitors was then confirmed to check the activity against ampC protein using an AutoDock tool. The results suggested OncoglabrinolC molecule as the best inhibitor (out of 21 drug molecules) with a binding affinity of - 11.44 kcal/mol. Anti-bacterial/anti-parasitic inhibitors have not only been used against bacterial infections, but later reports have also shown them to work against deadly viruses such as SARS-CoV2. This key structural and inhibitory information is certain to help in the discovery of specific and potent substitute therapeutic drugs and the development of experimental procedures against human infection.

Complex dynamics in susceptible-infected models for COVID-19 with multi-drug resistance.

Nowadays, exploring complex dynamic of epidemic models becomes a focal point for research after the outbreak of COVID-19 pandemic which has no vaccine or fully approved drug treatment up till now. Hence, complex dynamics in a susceptible-infected (SI) model for COVID-19 with multi-drug resistance (MDR) and its fractional-order counterpart are investigated. Existence of positive solution in fractional-order model is discussed. Local stability based on the fractional Routh-Hurwitz (FRH) conditions is considered. Also, new FRH conditions are introduced and proved for the fractional case (0,2]. All these FRH conditions are also applied to discuss local stability of the multi-drug resistance steady states. Chaotic attractors are also found in this model for both integer-order and fractional-order cases. Numerical tools such as Lyapunov exponents, Lyapunov spectrum and bifurcation diagrams are employed to confirm existence of these complex dynamics. This study helps to understand complex behaviors and predict spread of severe infectious diseases such as COVID-19.