Keyword: Multidrug-Resistant Pathogens

ABSTRACT: The growing pace of antimicrobial resistance (AMR) is a serious threat to modern infectious disease control as it has significantly undermined the clinical value of the traditional antibiotics. Traditional antimicrobial agents, which act by preventing the growth of bacteria or causing cell death, place a lot of selection pressure on the microbial population, therefore, promoting the rapid emergence and spread of resistance determinants. Besides spurring the evolution of resistance, such strategies often destabilize commensal microbiota and help transfer resistance genes between different bacteria of various species. These restrictions have shown that there is an urgent need to establish alternative treatment measures capable of reducing infections and reducing evolutionary pressures that promote resistance. Anti-virulence therapy (AVT) has developed as an exciting paradigm which has sought to lay emphasis on the molecular aspects of bacterial pathogenicity, as opposed to microbial viability. AVTs are designed to disrupt virulence-related processes such as quorum sensing, toxin secretion, host adhesion, immune evasion, and nutrient acquisition by selectively interrupting virulence in endotoxin-producing bacteria with the aim of attenuating virulence and promoting host-mediated clearance without necessarily endangering the survival of bacteria. It is theorized that this mechanistic difference will decrease the selective advantage provided to resistant variants, which may retard the tempo of resistance emergence and dissemination in bacterial populations. In this case, we will analyze the mechanistic foundations of bacterial virulence and will compare the existing anti-virulence therapies used as therapeutic approaches and their application in an evolutionary context. We also evaluate the new preclinical and clinical findings under the effectiveness of AVTs, along with the most important translational obstacles in terms of pharmacological optimization, target specificity, and regulatory validation. Together, these observations provide support to anti-virulence interventions as complementary or alternative therapies to conventional antibiotics in the treatment of multidrug-resistant infections, and highlight the necessity of interdisciplinary collaboration in order to support the adoption of such interventions into new-generation antimicrobial treatment programs.