Content area
Campylobacteriosis is one of the most commonly identified human gastrointestinal zoonosis in the European Union (EU) [1, 2]. The predominant species which has significant contribution to incidence of human infections is Campylobacter jejuni which represent more than 90% of human infections [3, 4]. The main reservoir and source of transmission of Campylobacerto humans is handling, preparation ant consumption of contaminated food, notably of poultry meat. Other risk factors, including the environment and animal contact, unpasteurized milk or wild birds are potential sources of human campylobacteriosis [5–7].
While most Campylobacter infections are self-limiting and do not necessitate antibiotic treatment, but severe and prolonged cases should be treated with antimicrobials and especially in case of infection of young, elderly and in individuals with compromised immunity [8, 9]. Also, campylobacteriosis caused by drug-resistant strains require long treatment and are associated with an increased mortality [10]. In most cases antimicrobial agents used in the treatment of Campylobacterinfections are macrolides, such as erythromycin (ERY), fluoroquinolones (FQ), or ciprofloxacin. However, in some cases aminoglycosides could be also considered as alternative indicated for septicemia [3, 11].
For the past few years, a significant worldwide increase in antimicrobial resistance among Campylobacter strains has been noted [1, 10]. It is important to note that studies between 1997 and 2015 have revealed an 8.55% increase of fluoroquinolone (ciprofloxacin) resistant strains of C. jejuni [12]. Genetic determinants and mutations play significant roles in the transfer of resistance and suggest that natural transformation does not play a major role in the emergence of FQ-resistant (FQR) Campylobacter strains [13, 14]. Recently given scale of the problem by the World Health Organization (WHO) classified FQ-resistant Campylobacter as a high-priority antibioticresistant pathogen for which a new antimicrobials should be developed [15]. Moreover, the increasing level ofC. jejuniresistance to other important antimicrobials, such as macrolides, aminoglycosides and β-lactams, is becoming a major public health concern in Europe and some other parts of the world [11, 16].
Increased antimicrobial resistance of Campylobacter jejuni is mainly associated with single point mutations in the bacteria genome, whereas the horizontal gene transfer among bacterial isolates is considered as the main mediator of acquisition of antibiotic resistance [17, 18]. Mutations in the genes encoding antibiotic resistance reduce and eliminate the efficacy of antibiotics to affect target sites increasing antimicrobial resistance level [14, 19]. In addition to FQR in Campylobacter, point mutations mediate resistance to other antimicrobials, such as macrolides and β-lactams. Mutations in the genes encoding antibiotic targets help bacteria counteract the attack by antibiotics. A point mutation in the quinolone resistance-determining region (QRDR) of the gyrA gene is mainly responsible of resistance to fluoroquinolones [17, 20]. Macrolide resistance in C. jejuni is mainly mediated by a point mutations occurring transition at position 2058/2059 in domain V of the 23S rRNA gene as well as amino acid change in L4/L22ribosomal proteins [17, 21].
The point mutations regulating the expression of blaOXA-61 and blaOXA-184 genes are linked to high level resistance to β-lactams [22, 23]. In C. jejuni,tetracycline resistance is usually associated with the gene encoding the ribosomal protection protein (RPP) tet(O) gene carried on transmissible plasmids.