Multidrug resistance in Acinetobacter baumannii

Bakterija Acinetobacter baumannii je Gram-negativni kokobacil prirodno prisutan u vodi i tlu. Prošlih nekoliko desetljeća glavni je uzrok bolničkih infekcija. Zbog sposobnosti brzog stjecanja gena za otpornost na antibiotike, pronalazak prikladnog tretmana postaje sve problematičniji. Glavni mehanizmi rezistencije kod Gram-negativnih bakterija uključuju enzimatsku inhibiciju, modifikaciju mete djelovanja antibiotika, prekomjerna ekspresija efluks sustava i mutacije porina. Navedene strategije koristi i bakterija A. baumannii. Ova bakterija sadrži intrinzične i stečene enzime β-laktamaze, koje inhibiraju djelovanje β-laktama hidrolizom, i aminoglikozid-modificirajuće enzime, koji modificiraju molekule aminoglikozida prijenosom funkcionalne skupine. Primjer enzima koji modificira metu djelovanja aminoglikozida su 16S rRNA metilaze. Nadalje, mutacije u specifičnim genima uzrokuju promjenu naboja površine stanice bakterije, što odbija određene antibiotike i onemogućuje im interakciju s vanjskom membranom. Prisutnost insercijskih sekvenci ili mutacija u promotoru i operatoru često uzrokuje prekomjernu ekspresiju intrinzičnih efluks sustava, koji tada doprinose rezistenciji na velik broj antibiotika. Mutacije koje uzrokuju gubitak funkcije porina doprinose stupnju antibiotske rezistencije na način da se smanjuje propusnost vanjske membrane. Genetičke strukture poput insercijskih sekvenci, integrona, transpozona i otoka rezistencije široko su rasprostranjene u genomu A. baumannii. Ovi mobilni genetički elementi omogućuju A. baumannii stjecanje i akumuliranje, te rasprostiranje čimbenika rezistencije putem horizontalnog genskog prijenosa.Acinetobacter baumannii is a Gram-negative coccobacillus commonly found in soil and water. It has been a major cause of nosocomial infections for the past few decades and is becoming more and more difficult to treat due to its ability to rapidly acquire resistance determinants to different types of antibiotics. Main resistance mechanisms performed by Gram-negative bacteria include enzymatic inhibition, modifications of target molecules, overexpression of efflux systems and porin mutations. A. baumannii has intrinsic and acquired enzymes β-lactamases, that inhibit β-lactam action by hydrolysis, and aminoglycoside-modifying enzymes, that modify the aminoglycoside molecule by transfer of functional groups, represent enzymatic inhibition resistance strategy. Enzymes like 16S rRNA methylase has emerged in A. baumannii as aminoglycoside target modifying enzyme. Furthermore, mutations in specific genes result in modification of cell surface local charge, which repels certain antibiotics from interacting with the outer membrane. Intrinsically present efflux systems are contributing to resistance to wide range of antibiotics, when overexpressed due to the presence of IS elements or the mutation in promoter or operator sequences. Porin knockout mutations contribute to antimicrobial resistance in a way that it leads to reduced membrane permeability. Genetic structures such as insertion sequences, transposons, integrons and resistance islands are widely distributed throughout the genome of A. baumannii. Due to these mobile genetic elements, A. baumannii has a remarkable ability to acquire and accumulate, as well as disseminate resistance determinants by horizontal gene transfer