Çeşitli klinik örneklerden izole edilen acinetobacter spp. suşlarında quorum sensing ve antibiyotik direnç genleri̇ni̇n araştırılması
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Tarih
2024
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Necmettin Erbakan Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Son yıllarda dünya çapında giderek artan sıklıkta hastane kaynaklı salgınlarla gündeme gelen
Acinetobacter spp. sağlık hizmeti ilişkili enfeksiyonların önemli bir nedenidir. Özellikle çoklu ilaca dirençli
(MDR) A. baumannii'nin artık büyük klinik öneme sahip olduğu kabul edilmektedir. Bununla birlikte, diğer
birçok Acinetobacter türü de sağlık hizmeti ilişkili enfeksiyonlara neden olabilmektedir. Literatürde
Acinetobacter spp. ile ilgili daha önce karbapenem, kinolon ve tetrasiklin grubunun da dahil olduğu birçok
antibiyotik grubuna direnç raporlanmıştır.Özellikle dirençli A. baumannii enfeksiyonlarının tedavisinde son
çare olarak kullanılmakta olan polimiksinlere gelişen direncin de raporlanması ile birlikte, bu problem endişe
verici seviyeye tırmanmıştır. Bunun yanında A. baumannii’de quorum sensing (QS) sistemlerinin biyofilm
üretimi gibi çeşitli hücresel mekanizmalarda kilit rol oynadığı ve varolan antibiyotik direncinin güçlenmesine
sebep olduğu gösterilmiştir.
Acinetobacter spp.’de antibiyotik direncine yönelik bilgiler genellikle A. baumannii hakkındaki
araştırmalardan elde edilmiştir. Non-baumannii türlerin antibiyotik direnci ile ilgili mekanizmalar henüz
yeterince aydınlatılamamıştır. A. baumannii’de karbapenem direncinde AmpC, blaOXA-23, blaOXA-24,
blaOXA-51 ve blaOXA-58 genlerinin yanısıra blaVIM, blaIMP, blaSPM, blaGIM ve blaSIM gibi metallo-betalaktamaz
üretimini sağlayan genler sorumludur. Son çare antibiyotikler olarak kullanılmakta olan tigesiklin ve
kolistin direncinden sorumlu olan genler ise sırasıyla tet ve mcr genleridir.
Bakterilerdeki QS mekanizması, biyofilm üretimi vb. dirence katkı sağlayan ve virülansı arttıran bazı
yetenekleri organize etmektedir ve bu mekanizmayı inhibe edebilecek “Quorum Quencher” arayışı son
zamanlarda artmıştır. Bu tür bileşiklerin QS mekanizmasını inhibe etmesi ve dolayısıyla bakterilerde ilaç
direnci gelişimini azaltması/engellemesi beklenmektedir. QS sistemlerine sahip Acinetobacter spp.’lerin, bu
mekanizmayı regüle eden genleri abaI ve abaR genleridir.
Günümüzde bakteriler tüm antibiyotiklere karşı hayatta kalmak için farklı yollarla direnç geliştirme
yeteneğine sahiptirler. Bakteriler arasındaki QS mekanizmasının inhibe edilerek; bu sistemle regüle edilen
virülans faktörleri, biyofilm oluşumu ve bakteriyel direnç mekanizmalarının zayıflatılma stratejisi dirençli
bakteriyel enfeksiyonların önlenmesinde umut vaadetmektedir. Bu nedenle bakterilerin QS ve antibiyotik
direnç mekanizmaları arasındaki ilişkinin daha da aydınlatılması gerekmektedir.
Çalışmamızda çeşitli klinik örneklerden izole edilen, identifikasyonu MS MALDI-TOF (bioMerieux,
Marcy l'Etoile, France), antibiyotik duyarlılıkları BD Phoenix otomatize sistemi (Becton-Dickinson, ABD) ile
tespit edilmiş 99 adet Acinetobacter spp. suşu kullanılmıştır. AmpC, blaOXA-23, blaOXA-24, blaOXA-51,
blaOXA-58, blaVIM, blaIMP, blaSPM, blaGIM, blaSIM tetX, mcr-1 ve QS genleri olan abaI, abaR DNA izolasyonu ve RT-PCR ile tespit edilmiştir. QS genleri olan abaI ve abaR’nin her ikisini de taşıyan ve
taşımayan izolatlar iki ayrı grup olarak değerlendirilmiş ve bu gruplar arasındaki bahsi geçen antibiyotik direnç
genlerinin varlığı ve çeşitli antibiyotikler için direnç düzeyleri karşılaştırılmıştır. Çalışmamızda housekeeping
gen olarak 16s rRNA kullanılmıştır. Suşlardan izole edilen DNA Titertek Berthold Colibri Microvolume
Spectro Nanodrop ölçümü ve jel elektroforezi ile doğrulanmıştır.
Elde ettiğimiz bulgular, QS genleri ile blaOXA-51 ve blaOXA-23 genlerinin varlığı ve amikasin,
siprofloksasin, levofloksasin, imipenem ve meropenem direnci arasında ilişki olabileceğini destekler nitelikte
literatüre katkı sunmaktadır. Ancak bu alanda daha fazla çalışmaya ihtiyaç vardır. Acinetobacter
enfeksiyonlarında antibiyotik direnci ile mücadelede umut vadeden QS inhibisyonu stratejisinin ilerleme
kaydetmesi antibiyotik direnci ile mücadele alanında yeni bir dönemin başlangıcı olabilir. Çalışmamız bu
alandaki az sayıda araştırmadan biri olma özelliğini taşımaktadır.
Acinetobacter spp., which has become an increasingly common cause of hospital-acquired epidemics worldwide in recent years, is an important cause of nosocomial infections. In particular, multidrug-resistant (MDR) A. baumannii is now considered to be of great clinical importance. Besides, many other Acinetobacter species can also cause nosocomial infections. In the literature, resistance to many antibiotic groups, including carbapenem, quinolone and tetracycline groups, has been previously reported for Acinetobacter spp.. This problem has escalated to an alarming level, especially with reports of developing resistance to polymyxins, which are used as a last resort in the treatment of resistant A. baumannii infections. In addition, it has been shown that Quorum Sensing (QS) systems in A. baumannii play a key role in various cellular mechanisms such as biofilm production and strengthen existing antibiotic resistance. Information on antibiotic resistance in Acinetobacter spp. has generally been obtained from studies on A. baumannii. The mechanisms related to antibiotic resistance of non-baumannii species have not yet been sufficiently elucidated. In addition to the AmpC, blaOXA-23, blaOXA-24, blaOXA-51 and blaOXA-58 genes, genes that provide metallo-beta-lactamase production such as blaVIM, blaIMP, blaSPM, blaGIM and blaSIM are responsible for carbapenem resistance in A. baumannii. The genes responsible for resistance to tigecycline and colistin, which are used as antibiotics of last resort, are tet(X) and mcr-1 genes, respectively. The QS mechanism in bacteria organizes some abilities that contribute to resistance and increase virulence, such as biofilm production, and the search for "Quorum Quencher" that can inhibit this mechanism has increased recently. Such compounds are expected to inhibit the QS mechanism and thus reduce/prevent the development of drug resistance in bacteria. The genes that regulate this mechanism in Acinetobacter spp. with QS systems are abaI and abaR genes. Today, bacteria have the ability to develop resistance to all antibiotics in different ways to survive. By inhibiting the QS mechanism between bacteria; Virulence factors regulated by this system, biofilm formation and the strategy of weakening bacterial resistance mechanisms are promising in preventing resistant bacterial infections. Therefore, the relationship between QS and antibiotic resistance mechanisms of bacteria needs to be further elucidated. In our study, 99 Acinetobacter spp. isolated from various clinical samples were identified by VITEK MS MALDI-TOF (bioMerieux, Marcy l'Etoile, France) and their antibiotic susceptibilities were determined by the BD Phoenix automated system (Becton-Dickinson, USA). strain was used. AmpC, blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, blaVIM, blaIMP, blaSPM, blaGIM, blaSIM tetX, mcr-1 and QS genes abaI, abaR were detected by DNA isolation and RT-PCR. Isolates carrying and not carrying both the QS genes abaI and abaR were evaluated as two separate groups, and the presence of the mentioned antibiotic resistance genes and resistance levels for various antibiotics were compared between these groups. In our study, 16s rRNA was used as the housekeeping gene. DNA isolation was confirmed by Titertek Berthold Colibri Microvolume Spectro Nanodrop measurement and gel electrophoresis. Our findings contribute to the literature by supporting that the expression of QS genes and blaOXA-51 and blaOXA-23 genes may be related. Still, a lot of study has to be carried out in this area. The progress of the promising QS inhibition strategy in combating carbapenem resistance in Acinetobacter infections may be the beginning of a new era in the field of combating antibiotic resistance. Our study is one of the few studies conducted in this field.
Acinetobacter spp., which has become an increasingly common cause of hospital-acquired epidemics worldwide in recent years, is an important cause of nosocomial infections. In particular, multidrug-resistant (MDR) A. baumannii is now considered to be of great clinical importance. Besides, many other Acinetobacter species can also cause nosocomial infections. In the literature, resistance to many antibiotic groups, including carbapenem, quinolone and tetracycline groups, has been previously reported for Acinetobacter spp.. This problem has escalated to an alarming level, especially with reports of developing resistance to polymyxins, which are used as a last resort in the treatment of resistant A. baumannii infections. In addition, it has been shown that Quorum Sensing (QS) systems in A. baumannii play a key role in various cellular mechanisms such as biofilm production and strengthen existing antibiotic resistance. Information on antibiotic resistance in Acinetobacter spp. has generally been obtained from studies on A. baumannii. The mechanisms related to antibiotic resistance of non-baumannii species have not yet been sufficiently elucidated. In addition to the AmpC, blaOXA-23, blaOXA-24, blaOXA-51 and blaOXA-58 genes, genes that provide metallo-beta-lactamase production such as blaVIM, blaIMP, blaSPM, blaGIM and blaSIM are responsible for carbapenem resistance in A. baumannii. The genes responsible for resistance to tigecycline and colistin, which are used as antibiotics of last resort, are tet(X) and mcr-1 genes, respectively. The QS mechanism in bacteria organizes some abilities that contribute to resistance and increase virulence, such as biofilm production, and the search for "Quorum Quencher" that can inhibit this mechanism has increased recently. Such compounds are expected to inhibit the QS mechanism and thus reduce/prevent the development of drug resistance in bacteria. The genes that regulate this mechanism in Acinetobacter spp. with QS systems are abaI and abaR genes. Today, bacteria have the ability to develop resistance to all antibiotics in different ways to survive. By inhibiting the QS mechanism between bacteria; Virulence factors regulated by this system, biofilm formation and the strategy of weakening bacterial resistance mechanisms are promising in preventing resistant bacterial infections. Therefore, the relationship between QS and antibiotic resistance mechanisms of bacteria needs to be further elucidated. In our study, 99 Acinetobacter spp. isolated from various clinical samples were identified by VITEK MS MALDI-TOF (bioMerieux, Marcy l'Etoile, France) and their antibiotic susceptibilities were determined by the BD Phoenix automated system (Becton-Dickinson, USA). strain was used. AmpC, blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, blaVIM, blaIMP, blaSPM, blaGIM, blaSIM tetX, mcr-1 and QS genes abaI, abaR were detected by DNA isolation and RT-PCR. Isolates carrying and not carrying both the QS genes abaI and abaR were evaluated as two separate groups, and the presence of the mentioned antibiotic resistance genes and resistance levels for various antibiotics were compared between these groups. In our study, 16s rRNA was used as the housekeeping gene. DNA isolation was confirmed by Titertek Berthold Colibri Microvolume Spectro Nanodrop measurement and gel electrophoresis. Our findings contribute to the literature by supporting that the expression of QS genes and blaOXA-51 and blaOXA-23 genes may be related. Still, a lot of study has to be carried out in this area. The progress of the promising QS inhibition strategy in combating carbapenem resistance in Acinetobacter infections may be the beginning of a new era in the field of combating antibiotic resistance. Our study is one of the few studies conducted in this field.
Açıklama
Anahtar Kelimeler
Gen Ekspresyonu, Gene Expression, Antibiyotik Direnci, Antibiotic Resistance, Acinetobacter, Quorum sensing., Quorum Sensing.
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Gülbay, S. R. (2024). Çeşitli klinik örneklerden izole edilen acinetobacter spp. suşlarında quorum sensing ve antibiyotik direnç genleri̇ni̇n araştırılması. (Yayınlanmamış tıpta uzmanlık tezi) Necmettin Erbakan Üniversitesi, Tıp Fakültesi Temel Tıp Bilimleri Bölümü Tıbbi Mikrobiyoloji Anabilim Dalı, Konya.
