Table 2.

Pathogen-directed therapeutic strategy to combat superbug

Pathogen-directed therapeutics strategy	Characteristics
Neutralization of virulence factors	• One of the main cause of bacterial infection is the presence of virulence factors in the bacterial surface morphology • This factor helps bacteria in adherence to epithelial mucosal membrane, formation of biofilm, and intracellular invasion of host cells • Therapies that target neutralization of the bacterial virulence factor at genetic level can neutralize its harmful effect such as genetic engineering technique can significantly reduce shiga toxin production in vitro enteric mouse infection model
Blockage of epithelial adherence or Biofilm formation	• The small drug molecules with effective anti-adherence characteristics may help in resisting the bacterial infections and serve as alternative treatment option against these superbugs • In case of Pseudomonas aeruginosa, adhesion-mediated binding of mucosal pathogens with epithelial cell receptor in host organ and their mucosal binding to form a polymeric matrix or biofilm formation is considered as the initiation step of disease pathogenesis • Reduction of biofilm formation and enhancing its elimination could also be a helpful strategy in minimizing host toxicity
Monoclonal antibody (mAb)	• Immunotherapy via monoclonal antibodies are intended for binding to the surface of target site of the specific pathogen or antigen having virulence factors • These antibodies help in the clearance of phagocytic part of microorganism and thus eliminate their pathogenic effect
Strategies for toxin neutralization	• Bacteria toxin can be neutralized either by physical sequestration technique or altering the pathogen binding affinity toward host cell receptor • Pharmacological agents can be prepared that mimic the structural features of the cell membrane of host. This mechanism can sequester the toxins away from the target host cell
Reducing bacterial virulence factor changing gene expression	• Virstatin is a potent virulence inhibition agent active against Vibrio cholera that changes the gene expression by downregulating the dimerization of transcriptional activator • Further, it prevents the biogenesis of pilus, motility, and formation of biofilm in resistant pathogens • Regacin is another similar agent that also inhibits the pathogenic virulence factor by changing its gene expression
Interference with bacterial quorum sensing	• Quorum sensing (QS) is a process in which bacterial species released auto inducers to increase its concentration as a function of cell density • Many resistant bacteria species regulate gene expression within host tissue through quorum sensing • Recent studies found emergence of resistance against tobramycin used against Pseudomonas aeruginosa infections; however, the drugs like 6-gingerol (derived from ginger) is effective in such cases by competitively inhibiting autoinducers of resistant bacteria or inhibits QS. The combination of 6-gingerol derivative and tobramycin provides more effective inhibition of virulence factor of P. aeruginosa by inhibiting QS as well as biofilm production in comparison to single therapy. The anti-infective activity of this combination was further confirmed in an insect model using Tenebrio larvae. The results indicated strong inhibitory activity at very low dose of adjuvant and suggests combined therapy might act as effective strategy for the management of P. aeruginosa infections
Sensitization of the pathogen toward host innate immune clearance	• This can be a beneficial approach in treating the patient suffering resistant bacterial infections • When the multidrug-resistant pathogens cause chronic infection to an individual, it is important to identify the gene that is withdrawn by the resistant bacteria leading to its virulence • Thus, re-sensitization of the said gene can be helpful in initiating its immune destruction