Gentamicin and special-purpose antibiotics

Gentamicin antibiotic: a 30S prokaryotic ribosome  inhibitor (wiki)

Gentamicin anti­bi­otic: a 30S proka­ryotic ribo­some inhib­itor (wiki)

Gentamicin is an unusual anti­obi­otic with two prop­er­ties that make it par­tic­u­larly use­ful in plant cell cul­ture: it is auto­clavable so is added to media before autoclaving/sterilization, and it is act­ive against myco­plas­mas as well as gram pos­it­ive and gram neg­at­ive bac­teria. Over the last week, I too have been get­ting it. I dis­covered this way other unusual prop­er­ties: while nearly any other drug is meta­bol­ized in the body, gentamicin is excreted unchanged. There is also much more than the usual fuss in pre­scrib­ing it: care­ful does cor­rel­a­tion of ‘lean body weight’ against dose (7mg/kg up to 640mg max daily) , and blood test­ing after the first dose to check the excre­tion rate: it will bind to many molecules so travels slowly out of the sys­tem. It is given intra­ven­ously, diluted in c. 100ml of 0.9% saline, as it is not absorbed orally, so is a drug restric­ted to hospitals.

It is isol­ated from the gram-positive aer­obic and mycelial soil bac­terium Micromonospora pur­pureand was dis­covered in 1963. Despite both the name of the anti­bi­otic and spe­cies from which gentamicin is isol­ated, it is a white powder or clear solu­tion. Why is it spelt ‘-micin’ rather than the ‘-mycin’ of products from other mycelial bac­teria and fungi? It seems that aminoglyc­os­ide anti­bi­ot­ics from this genus end with –micin, to dis­tin­guish them from those from those isol­ated from Streptomyces with dif­fer­ent taxo­nomic affin­it­ies (e.g. neo­my­cin and streptomycin).
Gentamicin shares some prop­er­ties with another anti­bi­otic widely used in plant research, kana­my­cin: both are aminoglyc­os­ides and work partly by inter­ac­tion with the 30S sub­unit of proka­ryotic ribosomes, inhib­it­ing proka­ryotic pro­tein syn­thesis. However, the two anti­bi­ot­ics act inde­pend­ently, and there are res­ist­ance genes which con­fer res­ist­ance only to gentamicin. The 30S inhib­i­tion means these are two of the anti­bi­ot­ics act­ive against myco­plas­mas (http://www​.sig​maald​rich​.com/life-science/core–biore­agents/learning–cen­ter/antibiotic–selection.html). Interestingly, Micromonospora seems to gain res­ist­ance to its own anti­bi­otic through methyl­a­tion of 16S ribosomal RNA (rRNA) in the 30s ribosomes. Although res­ist­ance among other bac­teria is rare, this methyl­a­tion has recently appeared as a mech­an­ism of res­ist­ance against aminoglyc­os­ides among gram-negative patho­gens; given the thera­peutic use still, per­haps gentamicin res­ist­ance is not the ideal select­able marker to use in plasmids.

Editor Pat Heslop-Harrison. ORCID 0000-0002-3105-2167

Pat Heslop-Harrison is Professor of Molecular Cytogenetics and Cell Biology at the University of Leicester. He is also Chief Editor of Annals of Botany.