Identification of DNA gyrase Subunit a Mutations Associated with Ciprofloxacin Resistance in Staphylococcus aureus Isolated from Nasal Infection in Kurdistan-Iran

Abstract

Fluoroquinolone antibiotics such as ciprofloxacin are useful drugs against infections caused by Staphylococcus aureus and mutations in DNA gyrase which control bacterial DNA topology, can be one of the reason of occurrence resistance to this class of antibiotics. Therefore finding new mutations and study of the quinolone interaction with mutated GyrA can provide important issues for explanation resistance. In this study 5 ciprofloxacin resistance Staphylococcus aureus isolated among 50 collected S.aureus strains. By PCR testing, gyrA genes in resistance strains was amplified and nucleotide sequencing was done. Nucleotide sequences translate to amino acid sequences then by blastp homology between each GyrA mutant and reference GyrA were compared and mutations were recognized, at last molecular docking were done for GyrA protein and ciprofloxacin, based on free energy of binding decide if the mutations are responsible of resistance or not. The results show glutamic acid and threonine adjacent to each other in common positions 21-22, 32-33, 65-66, 84-85, 101-102, 106-107, 128-129 and 138-139 in all 5 strains were inserted . In order to finding association between mutations and ciprofloxacin resistance molecular docking by Molegro Virtual Docker 5.5 was done. Free energy of binding between reference GyrAciprofloxacin and mutant GyrA-ciprofloxacin were -92.3477 and -73.1642 respectively. We conclude different mutations can be affected structure of GyrA and make ciprofloxacin resistance. Finding these kinds of mutations are important and preventing them is indispensable.

Antimicrobial Resistance Profile and Quinolone Resistance Genes in Staphylococcus aureus from Patients Attending Federal Medical Centre Keffi, Nigeria

“…The detection of both plasmid mediated quinolone resistance (PMQR) genes (qnrB, qnrS and aac(6')-Ib-cr) and chromosomal mediated quinolone resistance (CMQR) genes (gyrA, gyrB, and parC) in the ciprofloxacin-resistant S. aureus isolates is an indication that these genes may be responsible for the observed resistance to ciprofloxacin. The detection of gyrA, gyrB and parC agrees with reports [14,27,43]. The occurrence rates of gyrA, and gyrB were similar and higher than that of parC [43] but not so as reported by [44].…”

“…And only a few resistances were observed in the fluoroquinolones (ciprofloxacin and levofloxacin) 19.6% and 5.9% respectively in the test. This observation is similar to that of 10% ciprofloxacin S. aureus resistance reported [14] from clinical isolate from nasal infection in Kurdistan-Iran, 9% ciprofloxacin as reported [22] in public hospitals in Ghana and 6.0% levofloxacin resistance as reported [10], generally indicating low resistance to the fluoroquinolone antibiotics. This suggest that these fluoroquinolone antibiotics may not have been misused indiscriminately or abused in those study locations, and thus remains a good drug of choice for the treatment of infections caused by S. aureus.…”

“…Fluoroquinolone resistant S. aureus have also been widely reported globally [3,8,14,21,36,43], [44]. The 19.6% (10/51) ciprofloxacin resistance observed in this study is low and less than the 32.6% and 34.8% resistance of S. aureus isolates to ciprofloxacin and ofloxacin respectively as reported [26], 58.0% resistance to ciprofloxacin reported [43] in methicillinresistant S. aureus clinical isolates in Cairo, 92.5% and 80.4% resistance of S. aureus isolates to ciprofloxacin and ofloxacin respectively reported [3].…”

“…Fluoroquinolones, of which ciprofloxacin is the most widely used, are broad-spectrum antibiotics with good activity against gram-positive organisms, including both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) [11,12,13,14]. This wide usage of FQs provides a selective advantage for the emergence of FQ-resistant S. aureus (FQRSA), especially among methicillin resistant S. aureus (MRSA) strains [3].…”

Incidence of Ciprofloxacin-Resistant of Methicillin Resistant Staphylococcus aureus isolated from Iraqi patients

“…The sequences of the PCR product was obtained and compared to sequences of gyrA and parC genes from NCBI, the results shown that 40 and 51 mutations in the forward and reverse strands, respectively, were detected in gyrA of the tested isolate; since gyrA encode for DNA gyrase. Such mutations would lead to amino acid substitutions, alter the target protein for fluoroquinolone structure and subsequently the fluoroquinolone binding affinity of the enzyme, leading to drug resistance [23]. On the other hand; after comparing the obtained sequence of parC from the tested isolate with sequences from NCBI, the result revealed complete similarity and no mutations were recorded.…”