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.
