In Silico Analysis of Resistance Gene Identifiers on Plasmids of blaNDM-5 Producing Carbapenem-Resistant Escherichia coli Strains Isolated in Humans and Animals

Abstract

Due to their ability to resist endpoint antimicrobials such as carbapenem, it is very important to detect and monitor multi-drug resistant Gram negative strains with plasmids containing genes such as blaNDM-5 by new molecular methods. This study aimed to perform in silico analysis of resistance gene identifiers on human and animal-derived blaNDM-5 plasmids found in open databases, which were analyzed by new whole genome sequencing techniques and to compare these resistance genes. The plasmid genomic sequences of 4 human and 2 animal E. coli strains containing blaNDM-5 genes included in our study were analyzed in Silico using the Resistance Gene Identifier (RGI) option of the comprehensive antibiotic resistance gene database using default values. Human and animal strains included in our study were found to have different antimicrobial resistance genes in addition to blaNDM-5. All plasmids were found to have at least 8 perfect antimicrobial resistance gene sequences matches. When the resistance gene identifiers in all plasmids were examined, 35 resistance gene identifiers were found. Besides blaNDM-5, mphA, qacEdelta1 and sul1 were found in all plasmids. As a conclusion, it was determined by our study results that, regardless of the source, there may be different antimicrobial resistance gene identifiers besides the blaNDM-5 resistance gene in plasmids. We are of the opinion that routine molecular surveillance studies should be carried out considering the one health approach of Gram-negative pathogens such as E. coli, which can contain plasmids that cause multi-drug resistance and can be isolated from all sources.

Keywords

• bla-NDM5
• Carbapenem resistant E.coli
• in silico analysis
• resistance gene identifier

İnsanlardan ve Hayvanlardan İzole Edilen blaNDM-5 Üreten Karbapenem Dirençli Escherichia coli Kökenlerinin Plazmidlerı Üstünde Bulunan Direnç Gen Tanımlayıcılarının İn Silico Analizi

Öz

Karbapenem gibi son nokta antimikrobiyallere direnç yetenekleri dolayısıyla, blaNDM-5 gibi genler ihtiva eden plazmidlere sahip çoklu ilaç direnci gösteren Gram negatif kökenlerin yeni moleküler yöntemlerle tespiti önemlidir. Biz de çalışmamızda bu yeni tekniklerle tüm genom sekans analizi yapılan ve açık veritabanlarında bulunan insan ve hayvan kaynaklı blaNDM-5 plazmidleri üstünde bulunan direnç gen tanımlayıcılarının in silico analizini yapmayı ve bu direnç genlerini karşılaştırmayı amaçladık. Çalışmamıza dahil edilen 4 insan ve 2 hayvan kaynaklı, blaNDM-5 geni içeren E.coli kökenlerine ait plazmid genomik dizileri, varsayılan değerler kullanılarak kapsamlı antibiyotik direnç gen veritabanının, direnç geni tanımlayıcı (RGI) seçeneği kullanılarak bilgisayar ortamında analiz edildi. Çalışmamıza dahil edilen insan ve hayvan kaynaklı kökenlerde blaNDM-5 yanında farklı antimikrobiyal direnç genlerinin de olduğu tespit edildi. Tüm plazmidlerin en az 8 mükemmel antimikrobiyal direnç gen dizisi eşleşmesi gösterdiği saptandı. Tüm plazmidlerde bulunan direnç gen tanımlayıcıları incelendiğinde 35 direnç gen tanımlayıcısı saptandı. blaNDM-5 yanında, mphA, qacEdelta1 ve sul1’in bütün plazmidlerde olduğu tespit edildi. Sonuç olarak, kaynak fark etmeksizin, plazmidlerde, blaNDM-5 direnç geni yanında farklı antimikrobiyallere direnç gen tanımlayıcılarının da olabildiği çalışma sonucunda tespit edilmiştir. Çoklu ilaç direncine neden olan plazmidleri ihtiva edebilen ve tüm kaynaklardan izole edilebilen E. coli gibi Gram negatif patojenler üzerinde tek sağlık yaklaşımı düşünülerek rutin moleküler surveyans çalışmalarının yapılması gerektiği kanaatindeyiz.

Anahtar Kelimeler

• blaNDM-5
• direnç gen tanımlayıcıları
• in silico analiz Karbapenem dirençli E.coli

Kaynakça

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