scholarly journals Interaction between Mutations and Regulation of Gene Expression during Development ofDe NovoAntibiotic Resistance

2014 ◽  
Vol 58 (8) ◽  
pp. 4371-4379 ◽  
Author(s):  
Nadine Händel ◽  
Jasper M. Schuurmans ◽  
Yanfang Feng ◽  
Stanley Brul ◽  
Benno H. ter Kuile

ABSTRACTBacteria can become resistant not only by horizontal gene transfer or other forms of exchange of genetic information but also byde novoby adaptation at the gene expression level and through DNA mutations. The interrelationship between changes in gene expression and DNA mutations during acquisition of resistance is not well documented. In addition, it is not known whether the DNA mutations leading to resistance always occur in the same order and whether the final result is always identical. The expression of >4,000 genes inEscherichia coliwas compared upon adaptation to amoxicillin, tetracycline, and enrofloxacin. During adaptation, known resistance genes were sequenced for mutations that cause resistance. The order of mutations varied within two sets of strains adapted in parallel to amoxicillin and enrofloxacin, respectively, whereas the buildup of resistance was very similar. No specific mutations were related to the rather modest increase in tetracycline resistance. Ribosome-sensed induction and efflux pump activation initially protected the cell through induction of expression and allowed it to survive low levels of antibiotics. Subsequently, mutations were promoted by the stress-induced SOS response that stimulated modulation of genetic instability, and these mutations resulted in resistance to even higher antibiotic concentrations. The initial adaptation at the expression level enabled a subsequent trial and error search for the optimal mutations. The quantitative adjustment of cellular processes at different levels accelerated the acquisition of antibiotic resistance.

Genetics ◽  
1984 ◽  
Vol 108 (3) ◽  
pp. 651-667
Author(s):  
Douglas P Dickinson ◽  
Kenneth W Gross ◽  
Nina Piccini ◽  
Carol M Wilson

ABSTRACT Inbred strains of mice carry Ren-1, a gene encoding the thermostable Renin-1 isozyme. Ren-1 is expressed at relatively low levels in mouse submandibular gland and kidney. Some strains also carry Ren-2, a gene encoding the thermolabile Renin-2 isozyme. Ren-2 is expressed at high levels in the mouse submandibular gland and at very low levels, if at all, in the kidney. Ren-1 and Ren-2 are closely linked on mouse chromosome 1, show extensive homology in coding and noncoding regions and provide a model for studying the regulation of gene expression. An investigation of renin genes and enzymatic activity in wild-derived mice identified several restriction site polymorphisms as well as putative variants in renin gene expression and protein structure. The number of renin genes carried by different subpopulations of wild-derived mice is consistent with the occurrence of a gene duplication event prior to the divergence of M. spretus (2.75-5.5 million yr ago). This conclusion is in agreement with a prior estimate based upon comparative sequence analysis of Ren-1 and Ren-2 from inbred laboratory mice.


Author(s):  
Zahra Meshkat ◽  
Himen Salimizand ◽  
Yousef Amini ◽  
Davood Mansury ◽  
Abolfazl Rafati Zomorodi ◽  
...  

AbstractAcinetobacter baumannii, as a nosocomial pathogen has become a worldwide concern in recent years. In the current study, the resistance to tetracyclines and colistin were assessed in the isolates from different provinces of Iran.During the timeline of this study, a number of 270 isolates of A. baumannii were collected from tracheal aspirates, wounds, urine and blood cultures. The minimum inhibitory concentration (MIC) for tetracycline, doxycycline, minocycline, tigecycline and colistin were evaluated. Tetracycline resistance genes were assessed by PCR. The mean expression level of adeB, adeJ and adeG were assessed using semi quantitative Real-Time PCR. The clonal relationship of the isolates was evaluated by the repetitive extragenic palindromic PCR (REP-PCR), International Clonal (IC) Lineage Multiplex PCR and multilocus sequence typing (MLST) (Pasteur scheme) methods.The MIC by microdilution method showed that 87.5, 51.4, 28, 0.74 and 0% of the isolates were resistant to tetracycline, doxycycline, minocycline, tigecycline and colistin respectively. The prevalence of tetracycline resistance genes was 99.2, 99.2, 98, 86.7, 10, 3.33, 0.37, 0% for adeB, adeJ, adeG, tetB, tetA(39), tetA, tetM and tetH in tetracycline-resistant isolates. Moreover, the expression level of adeB, adeJ, adeG genes in tigecycline-nonsusceptible A. baumannii (TNAB) strain was higher compared to the tigecycline-susceptible A. baumannii (TSAB). A broad genomic diversity was revealed, but ST2 was the most prevalent ST. Our results indicated that tetracycline resistance in Iran is mediated by resistance-nodulation-cell division (RND) and tetB efflux pumps.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4677-4677
Author(s):  
Bing Xu ◽  
Xiaoyan Song ◽  
Pengcheng Shi ◽  
Pengnan Xiao ◽  
Zhengshan Yu ◽  
...  

Abstract Abstract 4677 Introdution The expression of CD56 antigen and over-expression of the multidrug resistance gene 1 (MDR1) seems to confer the poor therapeutic outcome to AML. The aim of this study is to investigate the relationship between CD56 antigen expression and MDR1 gene expression in patients with de novo AML and explore the indicating effect of these two factors on clinical drug resistance. Patients and methods A real-time quantitative reverse transcriptase polymerase chain reaction method was established for detecting MDR1 expression levels and a three-color flow cytometry analysis with CD45/SSC gating was used to examine CD56 antigen expression in 79 patients with de novo AML. Results CD56 antigen was recorded in 19 out of 79 cases (24.1%) and particularly in those with M5 subtype and t(8;21) AML. Moreover, CD56 expression was significantly associated with unfavorable cytogenetic abnormalities (P< 0.05). Significantly higher percentage (57.1%, 4/7) of patients with t(8;21) demonstrated CD56 expression than those with favorable cytogenetic abnormalities (P< 0.05). CD56+ AML patients had higher incidence of splenohepatomegalia and level of lactate dehydrogenase than CD56- patients (P< 0.05). The median expression level of MDR1 was statistically higher in CD56+ AML patients than that in CD56- cases (P< 0.001) and 89.5% (17/19) CD56+ AML patients were found with high MDR1 expression. The CR rate in high MDR1 / CD56+ AML patients was significantly lower than that in low MDR1/ CD56- cases. (58.8% vs 89.2%, P< 0.01). Conclusions There is a linear correlation between MDR1 and CD56 expression in AML. This relationship may explain why CD56 expression is related to a poor prognosis in AML. Therefore both with high MDR1 expression level and CD56 antigen expression can identify AML patients with unfavorable outcome. Disclosures: No relevant conflicts of interest to declare.


2016 ◽  
Vol 82 (15) ◽  
pp. 4456-4469 ◽  
Author(s):  
Claudia Guldimann ◽  
Kathryn J. Boor ◽  
Martin Wiedmann ◽  
Veronica Guariglia-Oropeza

ABSTRACTGram-positive bacteria are ubiquitous and diverse microorganisms that can survive and sometimes even thrive in continuously changing environments. The key to such resilience is the ability of members of a population to respond and adjust to dynamic conditions in the environment. In bacteria, such responses and adjustments are mediated, at least in part, through appropriate changes in the bacterial transcriptome in response to the conditions encountered. Resilience is important for bacterial survival in diverse, complex, and rapidly changing environments and requires coordinated networks that integrate individual, mechanistic responses to environmental cues to enable overall metabolic homeostasis. In many Gram-positive bacteria, a key transcriptional regulator of the response to changing environmental conditions is the alternative sigma factor σB. σBhas been characterized in a subset of Gram-positive bacteria, including the generaBacillus,Listeria, andStaphylococcus. Recent insight from next-generation-sequencing results indicates that σB-dependent regulation of gene expression contributes to resilience, i.e., the coordination of complex networks responsive to environmental changes. This review explores contributions of σBto resilience inBacillus,Listeria, andStaphylococcusand illustrates recently described regulatory functions of σB.


2015 ◽  
Vol 103 (1) ◽  
pp. 40-43 ◽  
Author(s):  
Mina Kazemzadeh ◽  
Reza Safaralizadeh ◽  
Mohammad Ali HosseinPour feizi ◽  
Mohammad Hossein Somi ◽  
Behrooz Shokoohi

Background Long non-coding RNAs (lncRNAs), a class of regulatory RNAs, play a major role in various cellular processes. Long intergenic non-coding RNAs (lincRNAs), a subclass of lncRNAs, are involved in the trans- and cis-regulation of gene expression. In the case of cis-regulation, by recruiting chromatin-modifying complexes, lincRNAs influence adjacent gene expression. Methods We used quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to evaluate the coexpression of LOC100287225, a lincRNA, and DCC, one of its adjacent genes that is often decreased in colorectal cancer, in pairs of tumor and adjacent tumor-free tissues of 30 colorectal cancer patients. Results The qRT-PCR results revealed the misregulation of these genes during tumorigenesis. Their relative expression levels were significantly lower in tumor tissues than adjacent tumor-free tissues. However, the analysis found no significant correlation between reduced expression of these genes. Conclusions Our study demonstrated the concurrent misregulation of DCC and LOC100287225 in colorectal cancer.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Guangbing Li ◽  
Haohai Zhang ◽  
Xueshuai Wan ◽  
Xiaobo Yang ◽  
Chengpei Zhu ◽  
...  

Long noncoding RNAs (lncRNAs) have been attracting immense research interests. However, only a handful of lncRNAs had been thoroughly characterized. They were involved in fundamental cellular processes including regulation of gene expression at epigenetics as well as tumorogenesis. In this paper, we give a systematic and comprehensive review of existing literature about lncRNA involvement in hepatocellular carcinoma. This review exhibited that lncRNAs played important roles in tumorigenesis and subsequent prognosis and metastasis of hepatocellular carcinoma and elucidated the role of some specific lncRNAs such as MALAT1 and HOTAIR in the pathophysiology of hepatocellular carcinoma and their potential of being therapeutic targets.


2012 ◽  
Vol 78 (16) ◽  
pp. 5699-5707 ◽  
Author(s):  
James Matsunaga ◽  
Mariana L. Coutinho

ABSTRACTLeptospirosis is a potentially deadly zoonotic disease that afflicts humans and animals.Leptospira interrogans, the predominant agent of leptospirosis, encounters diverse conditions as it proceeds through its life cycle, which includes stages inside and outside the host. Unfortunately, the number of genetic tools available for examining the regulation of gene expression inL. interrogansis limited. Consequently, little is known about the genetic circuits that control gene expression inLeptospira. To better understand the regulation of leptospiral gene expression, theL. interrogans kdplocus, encoding homologs of the P-type ATPase KdpABC potassium transporter with their KdpD sensors and KdpE response regulators, was selected for analysis. We showed that akdpEmutation inL. interrogansprevented the increase inkdpABCmRNA levels observed in the wild-typeL. interrogansstrain when external potassium levels were low. To confirm that KdpE was a positive regulator ofkdpABCtranscription, we developed a novel approach for constructing chromosomal genetic fusions to the endogenousbgaL(β-galactosidase) gene of the nonpathogenLeptospira biflexa. We demonstrated positive regulation of akdpA′-bgaLfusion inL. biflexaby theL. interrogansKdpE response regulator. A controllipL32′-bgaLfusion was not regulated by KdpE. These results demonstrate the utility of genetic fusions to thebgaLgene ofL. biflexafor examining leptospiral gene regulation.


2021 ◽  
Vol 12 ◽  
Author(s):  
Suresh Kumar ◽  
Trilochan Mohapatra

Epigenetic modifications in DNA bases and histone proteins play important roles in the regulation of gene expression and genome stability. Chemical modification of DNA base (e.g., addition of a methyl group at the fifth carbon of cytosine residue) switches on/off the gene expression during developmental process and environmental stresses. The dynamics of DNA base methylation depends mainly on the activities of the writer/eraser guided by non-coding RNA (ncRNA) and regulated by the developmental/environmental cues. De novo DNA methylation and active demethylation activities control the methylation level and regulate the gene expression. Identification of ncRNA involved in de novo DNA methylation, increased DNA methylation proteins guiding DNA demethylase, and methylation monitoring sequence that helps maintaining a balance between DNA methylation and demethylation is the recent developments that may resolve some of the enigmas. Such discoveries provide a better understanding of the dynamics/functions of DNA base methylation and epigenetic regulation of growth, development, and stress tolerance in crop plants. Identification of epigenetic pathways in animals, their existence/orthologs in plants, and functional validation might improve future strategies for epigenome editing toward climate-resilient, sustainable agriculture in this era of global climate change. The present review discusses the dynamics of DNA methylation (cytosine/adenine) in plants, its functions in regulating gene expression under abiotic/biotic stresses, developmental processes, and genome stability.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5316-5316
Author(s):  
Bing Xu ◽  
Huijuan Dong ◽  
Feili Chen ◽  
Yong Zhou ◽  
Jiabao Liang ◽  
...  

Abstract Background: I-mfa has been identified as an inhibitor of MyoD and other related myogenic basic helix-loop-helix proteins. I-mfa contains a cysteine-rich C-terminal domain, and has been reported to function as transcriptional regulator of different pathways including Wnt signaling, c-jun N-terminal kinase signaling, and the regulatory properties of I-mfa depend on the C-terminal domain. Furthermore, recent studies have found that the I-mfa domain may have a close correlation with the development of myeloid neoplasms, however the role of I-mfa in adult patients with de novo acute myeloid leukemia still remain unclear. Aims: The aim of this study was to determine I-mfa expression in adult patients with de novo acute myeloid leukemia and its clinical significance. Methods: BM samples form 110 adult patients with de novo AML were analyzed. Of the 110 AML patients, 66 were males and 44 were females, with a mean age of 32 years( range from 12 to 77 years). Among them, 1 out of 110 patients was M1, 49 were M2, 14 were M4, 28 were M5, 1was M6 and 17 were acute unclassified leukemia. All patients received 1 to 2 cycles of induction of standard-dose cytarabine continuous infusion×7 days with idarubicin or daunorubicin×3days, fellowed by consolidation therapy with HiDAC and then stem cell transplantation according to patient’s condition. Real-time reverse transcription-polymerase chain reaction(RT-PCR) was used to detect the expression of I-mfa gene in 110 de novo adult AML patients, and the patients were divided into high and low I-mfa expression groups accordint to the median expression of I-mfa mRNA. Comparisons were performed using Mann-Whitney U test, Chi-square test and Kaplan-Meier method. Results:Distribution of I-mfa gene expression in different FAB subtypes was with no significant differences (P=0.169). The median age of AML pateints in low and high I-mfa gene epxression groups were 35 and 40 years old(P=0.162), and the median expression of I-mfa in 44 female patients and 66 male patients was 0.018 and 0.013 separately(P=0.728). What’s more, there was no significant difference of WBC, Hb level, PLT, bone marrow blast counts between the two groups (P>0.05), and the I-mfa expression level was also not correlated with chromosome risk stratification and the expression of CD34 (P>0.05). High I-mfa expression group had a lower complete remission rate than that in the low expression group (81.8% vs 63.6%, P=0.032), However, the overall survival rate was with no significant difference in the low and hign I-mfa gene expression groups(76.4% vs 76.4%, P=0.471). Conclusions: Our results showed high I-mfa expression correlates with a poor treatment response, the OS rate was with no significant difference in the two groups. There is somewhat correlation between the expression level of I-mfa gene and prognosis and the expression of I-mfa may be a prognostic factor for adult patients with de novo acute myeloid leukemia. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yoshihisa Ikeda ◽  
David Zalabák ◽  
Ivona Kubalová ◽  
Michaela Králová ◽  
Wolfram G. Brenner ◽  
...  

Among the major phytohormones, the cytokinin exhibits unique features for its ability to positively affect the developmental status of plastids. Even early on in its research, cytokinins were known to promote plastid differentiation and to reduce the loss of chlorophyll in detached leaves. Since the discovery of the components of cytokinin perception and primary signaling, the genes involved in photosynthesis and plastid differentiation have been identified as those directly targeted by type-B response regulators. Furthermore, cytokinins are known to modulate versatile cellular processes such as promoting the division and differentiation of cells and, in concert with auxin, initiating the de novo formation of shoot apical meristem (SAM) in tissue cultures. Yet how cytokinins precisely participate in such diverse cellular phenomena, and how the associated cellular processes are coordinated as a whole, remains unclear. A plausible presumption that would account for the coordinated gene expression is the tight and reciprocal communication between the nucleus and plastid. The fact that cytokinins affect plastid developmental status via gene expression in both the nucleus and plastid is interpreted here to suggest that cytokinin functions as an initiator of anterograde (nucleus-to-plastid) signaling. Based on this viewpoint, we first summarize the physiological relevance of cytokinins to the coordination of plastid differentiation with de novo shoot organogenesis in tissue culture systems. Next, the role of endogenous cytokinins in influencing plastid differentiation within the SAM of intact plants is discussed. Finally, a presumed plastid-derived signal in response to cytokinins for coupled nuclear gene expression is proposed.


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