摘要：The emergence of resistance to antimicrobial agents is a pressing concern for human health that increases the need for the development of novel antimicrobial drugs. Antimicrobial resistance means that microorganism keep on growing even in the presence of a drug due to specific defense mechanisms [e.g. efflux-pumps]. Many of infectious diseases are difficult to be treated with antimicrobials not due to resistance but persisters [non-multiplying cells]. Distinction is important as persistent cells need an entirely design of new antimicrobial agents. Non-multiplying cells, do not cause overt disease but prolong the duration of therapy, increasing the chance of the emergence of resistance [i.e. bacterial or fungal biofilms and latent tuberculosis] resulting in therapy failure. Persisters are phenotypic variants of the wild type that present in all microorganisms which are able to survive antimicrobial treatment without acquiring resistance-conferring genetic changes and upon re-growth they produce a population of sensitive cells and new persisters. Persistence may arise spontaneously regardless to the presence of drug or environmentally induced due to starvation, DNA damage, oxidative stress and quorum sensing. Many approaches targeting non-multipliers would shorten the duration of therapy and decrease the emergence of resistance. Some depends on studying the effectiveness of the existing therapeutics against non-multipliers [i.e. pyrazinamide and gatifloxacin] and others depend on the discovery of new compounds targeting microbial genes that might be essential to non-multipliers viability or specific enzymatic or metabolic pathway [i.e. TG44 targets outer membrane of Helicobacter pylori and TMC207 targets proton pump of the ATP synthetase in Mycobacterium tuberculosis]. Clinical trials and studies are needed to produce a marketed antimicrobial agent active against both multiplying and non multiplying organisms and to know whether the approach of targeting non-multiplying bacteria is clinically relevant and will produce compounds that reduce the rate of emergence of bacterial resistance.
