Abstract
Acinetobacter baumannii (A. baumannii) has developed several resistance mechanisms. The bacteria have been reported as origin of multiple outbreaks. This study aims to investigate the use of efflux pumps and quinolone resistance-associated genotypic mutations as mechanisms of resistance in A. baumannii isolates at a tertiary hospital. A total number of 103 A. baumannii isolates were investigated after identification and antimicrobial susceptibility testing by VITEK2 followed by PCR amplification of blaOXA-51. Conventional PCR amplification of the AdeABC efflux pump (adeB, adeS, and adeR) and quinolone (parC and gyrA) resistance genes were performed, followed by quantitative real-time PCR of AdeABC efflux pump genes. Phenotypic evaluation of efflux pump expression was performed by determining the difference between the MIC of tigecycline before and after exposure to an efflux pump inhibitor. The Sanger sequencing method was used to sequence the parC and gyrA amplicons. A phylogenetic tree was drawn using MEGA 4.0 to evaluate evolutionary relatedness of the strains. All the collected isolates were blaOXA-51-positive. High resistance to almost all the tested antibiotics was observed. Efflux pump was found in 75% of isolates as a mechanism of resistance. The study detected parC gene mutation in 60% and gyrA gene mutation in 85%, while 37% of isolates had mutations on both genes. A minimal evolutionary distance between the isolates was reported. The use of the AdeABC efflux pump system as an active mechanism of resistance combined with point mutation mainly in gyrA was shown to contribute to broaden the resistance spectrum of A. baumannii isolates.
Highlights
Acinetobacter baumannii (A. baumannii) is one of the nosocomial pathogens that exhibits high level of resistance to antibiotics [1, 2]. is Gram-negative coccobacillus bacterium is responsible for infections predominantly in the intensive care unit [3, 4]. e bacterium causes pneumonia, bacteraemia, septicaemia [5], meningitis [6], and urinary tract infections [7] often seen in patients undergoing invasive procedures such as urinary catheter, tracheal intubation, and those with underlying conditions [2]
International Journal of Microbiology developed antibiotics such as eravacycline [15] and cefiderocol [16]. e bacterium has acquired several resistance mechanisms through mobile genetic elements [17, 18] and has shown to have natural resistance against some antibiotics including aminopenicillins, first and second generation cephalosporins, aztreonam, ertapenem, fosfomycin, chloramphenicol, and trimethoprim [19] leading to emergence of multidrug and pandrug-resistant strains [8, 9]. e main mechanisms expressed by A. baumannii to escape antibiotics attack are production of antibiotichydrolysing enzymes, poor membrane penetration, permeability defects, alteration of target sites or cellular functions, and active efflux pumps [20]
Efflux pumps are the main mediators of resistance mechanisms against many antibiotic classes [21]. rough this mechanism, the bacteria avoid accumulation of drugs at the targeted site within it, leading to decreased susceptibility to antibiotics [17, 21]. ree resistance-nodulation-cells division encoded in A. baumannii genome is reported to contribute to antibiotic resistance in A. baumannii clinical isolates [22]. e overexpression of efflux pumps in A. baumannii has been associated with an increased resistance to antibiotics such as tigecycline [14, 23], carbapenems [24], minocycline, gentamycin, doxycycline, and tetracycline [25]
Summary
Acinetobacter baumannii (A. baumannii) is one of the nosocomial pathogens that exhibits high level of resistance to antibiotics [1, 2]. is Gram-negative coccobacillus bacterium is responsible for infections predominantly in the intensive care unit [3, 4]. e bacterium causes pneumonia, bacteraemia, septicaemia [5], meningitis [6], and urinary tract infections [7] often seen in patients undergoing invasive procedures such as urinary catheter, tracheal intubation, and those with underlying conditions [2]. A. baumannii has demonstrated several antimicrobial resistance mechanisms [8,9,10] against antibiotics such as aminoglycosides, carbapenems, fluoroquinolones, cephalosporins, tetracyclines, sulbactams, rifampicins [9], as well as colistin [11,12,13] and tigecycline [8, 14], the so called last resort drugs used to treat its infections [8, 11,12,13,14]. Is mechanism of resistance reduces the susceptibility of A. baumannii to multiple class of antibiotics [23, 28,29,30] and has been reported to be associated with resistance to newly developed drugs [30]. Literature supports that a single mutation in gyrA inducing an amino acid change from serine to leucine in position 83 (serine 83) reduces the susceptibility of A. baumannii clinical isolates to fluoroquinolones [40]. Two mutations in parC in position 80 (serine 80) and 84 (Glu-84) inducing change from serine to isoleucine and glutamic acid into valine, respectively, lead to resistance to fluoroquinolones [40]
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