Evolution of microbial resistance, particularly in Gram-negative bacteria, became a nightmare for the healthcare professionals and contributed effectively to high treatment failures as well as infection-related mortality rates. Understanding the diverse mechanisms by which the organisms acquire and transmit these resistance trends is a key determining step in any research endeavors aiming to develop either new drug molecules or treatment guidelines.
Gram-negative bacteria develop resistance through several mechanisms that render it less susceptible or even absolutely resistant to clinically relevant antibiotics. Enzymatic deactivation is the most common bacterial defense mechanism, in addition to other molecular mechanisms like decreased cell wall permeability through down-regulation of its porins, or over-expression of efflux pumps responsible for the decreased intracellular minimum inhibitory concentration of antibiotics, biofilm construction which is a protective barrier against threatening from bacterial surroundings, and antibiotic-specific target modification that leads to impaired drug-target fitting resulting inferior or prohibited clinical response.
Keywords: Antibiotic-specific target, Down-regulation, Efflux pumps, Evolution, Gram-negative bacteria, Molecular basis, Resistance.