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    Analyses of the relationships among biofilm activity, antibiotic resistance and expressions of SHV, TEM, CTXand IntI in Klebsiella pneumoniae
    (2021) Güçkan, Rıdvan; Kılınç, Çetin; Başkan, Ceren; Yazgan, Burak; Mesci, Seda; Yıldırım, Tuba
    Aim: Klebsiella pneumoniae as an opportunistic pathogen is responsible for nosocomial, urinary tract infections, pneumonia, bacteremia, liver abscesses, and respiratory and blood infections in patients. The aim of our study is to examine the antibiotic sensitivity, expression levels of IntI, TEM, SHV and CTX genes, which play a role in multidrug resistance, biofilm formation and even the relationships among them. Materials and Methods: Identification was implemented by carrying out the VITEK2 system and phenotypic confirmation of the ESBL producing isolates by using a combined disc test. Antibiotic sensitivity was implemented by disc diffusion method and microdilution methods toward various antibiotics. Furthermore, biofilm formation was examined through microtitration plate method. Results: The expressions of IntI, TEM, SHV and CTX were implemented in qRT-PCR. 19 were susceptible to all antibiotics, 17 were ESBL (+) and 16 were carbapenem-resistant among 52. The expression of these genes was upregulated in ESBL (+) strains and produced biofilm and the expression of these genes was upregulated, too. Conclusion: The results of the study revealed the potential role of the mentioned genes in biofilm formation and antibiotic resistance, enabling the development of new drugs. Further studies will be essential so as to determine when or how these systems are included in antibiotic resistance and biofilm formation.
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    Öğe
    Downregulation of HSP27 by isoindole-derived pyrrolidines suppressing multidrug resistance (MDR) and inducing apoptosis in MCF-7 and DLD-1 cell lines
    (NATL INST SCIENCE COMMUNICATION-NISCAIR, 2024) Mesci, Seda; Yazgan, Burak; Gül, Melek; Yıldırım, Tuba
    In most cancer treatments, major problem arises from the prevention of cell death (apoptosis suppression) with the development of drug resistance. Anticancer agents that ensure elimination of drug resistance and drug-resistant cells to apoptosis, are among the main targets. Here, we evaluated a series of synthesized N-phenyl maleimide substituents in tetracyclic compounds as anticancer drug candidate. We selected compounds may lead to death and eliminate drug resistance in breast and colon cells. In MCF-7 and DLD-1 cell lines; multidrug resistance genes (ABCB1, ABCC3, ABCC10, ABCC11 and ABCG2), apoptosis mechanism genes (BAX, BCL-2, p53, PARP and CASP3), heat shock genes (HSP27, HSP40, HSP60, HSP70 and HSP90?) and endoplasmic reticulum (ER) chaperone genes (GRP78 and GRP94) mRNA levels were determined by qPCR method. Amounts of proteins of apoptosis and signalling pathways were measured by human apoptosis antibody array. The compounds have been shown to have downregulation on multidrug resistance genes other than ABCC3. It was found that all compounds in MCF-7 and DLD-1 cells showed significant increase in p53, BAX and CASP3 gene expressions. Also, the compounds have the potential to reduce gene expression of heat shock genes (HSPs). While the compounds have been determined to increase protein expression in BAD, BAX, BID, BIM, Caspase-3, Caspase-7, Caspase-8, Cytochrome-C, Fas, TNF, TRAIL, p27, p38 and p53; decrease protein expression in AKT, BCL-2, ERK1/2, HSP27, HSP60, IGFs, JNK, NFKB, PARP, TAK1, Survivin in MCF-7 and DLD-1 cells. The compounds stand out with their inhibition of HSP27 in DLD-1 cells and their inhibition with HSP27 and NFkB in MCF-7 cells. Overall, it has been shown that these compounds increase intrinsic and extrinsic proapoptotic proteins, decrease antiapoptotic proteins, decrease HSPs and some growth factors, and they may serve as potential anticarcinogenic molecules.