The molecular biology of moenomycins: towards novel antibiotics based on inhibition of bacterial peptidoglycan glycosyltransferases

2010 ◽  
Vol 391 (5) ◽  
pp. 499-504 ◽  
Author(s):  
Bohdan Ostash ◽  
Emma Doud ◽  
Victor Fedorenko
Keyword(s):  
Molecular Biology ◽  
Natural Product ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Initial Characterization ◽  
Genetic Mechanisms ◽  
Bacterial Peptidoglycan ◽  
Peptidoglycan Glycosyltransferases ◽  
Novel Antibiotics

AbstractMoenomycins are phosphoglycolipid antibiotics and the only known natural product inhibitors of peptidoglycan glycosytransferases (PGTs). Techniques that would allow facile diversification of the moenomycin structure would facilitate the development of novel antibiotics, which are urgently needed in the wake of multidrug resistant bacterial infections. The cloning and initial characterization of the moenomycin biosynthetic genes has already redefined the minimal moenomycin pharmacophore and now opens the door for the biocombinatorial generation of bioactive moenomycin fragments. Here, we highlight the importance of research on the genetic mechanisms that regulate moenomycin biosynthesis and that confer moenomycin resistance to bacteria in the development of novel anti-infectives based on PGT inhibition.

scholarly journals Recent Progress in the Development of Small-Molecule FtsZ Inhibitors as Chemical Tools for the Development of Novel Antibiotics

Antibiotics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 217 ◽  
Author(s):  
Laura Carro
Keyword(s):  
Small Molecule ◽  
Bacterial Infections ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Bacterial Cell Division ◽  
Promising Target ◽  
Ftsz Inhibitors ◽  
Novel Antibiotics ◽  
Urgent Action

Antibiotics are potent pharmacological weapons against bacterial pathogens, nevertheless their efficacy is becoming compromised due to the worldwide emergence and spread of multidrug-resistant bacteria or “superbugs”. Antibiotic resistance is rising to such dangerous levels that the treatment of bacterial infections is becoming a clinical challenge. Therefore, urgent action is needed to develop new generations of antibiotics that will help tackle this increasing and serious public health problem. Due to its essential role in bacterial cell division, the tubulin-like protein FtsZ has emerged as a promising target for the development of novel antibiotics with new mechanisms of action. This review highlights the medicinal chemistry efforts towards the identification of small-molecule FtsZ inhibitors with antibacterial activity in the last three years.

scholarly journals Molecular Characterization of Multiple Antibiotic-Resistant Acinetobacter baumannii Isolated from Egyptian Patients

2020 ◽  
Vol 14 (4) ◽  
pp. 2399-2405
Author(s):  
Aya A. Khodier ◽  
Amal Saafan ◽  
Walid Bakeer ◽  
Ahmed S. Khairalla
Keyword(s):  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Class I ◽  
Pcr Analysis ◽  
Antibiotic Resistant ◽  
Egyptian Patients ◽  
Class I Integrons ◽  
Genetic Mechanisms ◽  
Hospital Acquired

Acinetobacter baumannii is an opportunistic microorganism commonly found in intensive care units (ICUs), and it is responsible for a broad span of hospital-acquired infections. Persistence of nosocomial infection caused by multidrug-resistant (MDR) A. baumannii is an alarming health care issue in Egypt, and at present, colistin remains the treatment of choice for the management of MDR A. baumannii infections. A. baumannii possesses great capacity to develop and acquire resistance to a broad range of antibiotics. The acquisition and dissemination of antibiotic-resistant determinants in A. baumannii strains are mediated by integrons, especially class I integrons. This study focuses on the characterization of some genetic mechanisms underlying the multidrug-resistant phenotypes of A. baumannii isolates in Egypt. Forty-eight A. baumannii specimens were isolated from different hospitalized patients; least resistance was observed against amikacin and tigecycline, with 60% and 58.5% of the isolates resistant, respectively, whereas 62.5% of the isolates were resistant to imipenem and meropenem. The highest sensitivity was found for colistin. Genetic analysis revealed that blaoxa-51 was detected in all isolates, the blaoxa-23-like gene was detected in 80% of the isolates, and blaoxa-24 and blaoxs-58 were not detected in any isolate. Finally, PCR analysis revealed that 6.6% of isolates carried the class I integron gene.

scholarly journals Characterization of Three Porcine Acinetobacter towneri Strains Co-Harboring tet(X3) and blaOXA-58

2020 ◽  
Vol 10 ◽  
Author(s):  
Jiangang Ma ◽  
Juan Wang ◽  
Jie Feng ◽  
Yingqiu Liu ◽  
Baowei Yang ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Multidrug Resistant ◽  
S1 Nuclease ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Nuclease Digestion ◽  
Insertion Elements ◽  
Backbone Structure ◽  
Multiple Antibiotics

Tigecycline is the antibiotic of last resort for the treatment of extensively drug-resistant bacterial infections, mainly those of multidrug-resistant Gram-negative bacteria. The plasmid-mediated tet(X3) gene has recently been described in various pathogens that are resistant to tigecycline. We report three tigecycline-resistant Acinetobacter towneri strains isolated from porcine faeces in China, which all contained the tet(X3)-harboring plasmids. A broth microdilution method was used to examine the antimicrobial susceptibility of the isolates, and S1-Nuclease digestion pulsed-field gel electrophoresis (S1-PFGE) was used to characterize their plasmid profiles. The whole-genome sequences of the isolates were determined with the Nanopore PromethION platform. The sequence analysis indicated that the strains were A. towneri. They showed resistance to multiple antibiotics, and all the resistance genes were located on plasmids. The three tet(X3)-harboring plasmids had a similar backbone structure, and all contained blaOXA-58 with various insertion elements (IS). ISCR2 is considered an important factor in tet(X3) mobilization. In addition to ISCR2, we demonstrate that IS26 generates a circular intermediate containing the tet(X3) gene, which could increase the dissemination risk. To our knowledge, this is the first report of tet(X3)- and blaOXA-58-harboring plasmids in A. towneri. Because the IS26 is frequently found in front of tet(X3), research should be directed toward the action of IS26 in the spread of tet(X3).

scholarly journals Clinically relevant infections in hematology and oncology: bacterial infections and the role of novel antibiotics in times of multidrug resistance

2021 ◽  
Author(s):  
Gernot Fritsche
Keyword(s):  
Multidrug Resistance ◽  
Antibiotic Therapy ◽  
Bacterial Infections ◽  
Empirical Therapy ◽  
Multidrug Resistant ◽  
Infectious Complications ◽  
Novel Drugs ◽  
New Antibiotics ◽  
Conventional Antibiotics ◽  
Novel Antibiotics

SummaryMultidrug resistance of bacterial pathogens is an increasing problem wordwide, especially treatment of multidrug resistant (MDR) gramnegative bacteria is challenging. In the recent past, several new antibiotics as well as new betalactamase inhibitors have been introduced. These novel drugs are valuable new tools for the therapy of infectious complications in cancer patients once there is a high risk for infections due to multidrug-resistant pathogens. While it is necessary to start empirical antibiotic therapy immediately, novel antibiotics only provide benefits in certain situations, depending on the underlying pathogens. Thus, these new antibiotics are best used guided by microbiological testing, since the exact mechanism of resistance determines susceptibility or resistance to certain antibiotics. For empirical therapy, previous culture results and/or colonization with MDR pathogens can help to choose from conventional antibiotics or novel drugs. In clinical practice, optimal antibiotic therapy can be achieved by close collaboration of specialists in hematooncology, infectious diseases and microbiology.

scholarly journals Characterization of antibiotic resistance in Listeria spp. isolated from slaughterhouse environments, pork and human infections

2014 ◽  
Vol 8 (04) ◽  
pp. 416-423 ◽  
Author(s):  
Luisa Z Moreno ◽  
Renata Paixão ◽  
Débora D. S. Gobbi ◽  
Daniele C. Raimundo ◽  
Thais P. Ferreira ◽  
...  
Keyword(s):  
Public Health ◽  
Antibiotic Resistance ◽  
Multidrug Resistant ◽  
Intrinsic Resistance ◽  
Health Concerns ◽  
Minimal Inhibitory Concentrations ◽  
Intermediate Resistance ◽  
Genetic Mechanisms ◽  
Human Infections

Introduction: Listeria species are susceptible to most antibiotics. However, over the last decade, increasing reports of multidrug-resistant Listeria spp. from various sources have prompted public health concerns. The objective of this study was to characterize the antibiotic susceptibility of Listeria spp. and the genetic mechanisms that confer resistance. Methodology: Forty-six Listeria spp. isolates were studied, and their minimal inhibitory concentrations of antibiotics were determined by microdilution using Sensititre standard susceptibility MIC plates. The isolates were screened for the presence of gyrA, parC, lde, lsa(A), lnu(A), and mprF by PCR, and the amplified genes were sequenced. Results: All isolates were susceptible to penicillin, ampicillin, tetracycline, erythromycin, and carbapenems. Resistance to clindamycin, daptomycin, and oxacillin was found among L. monocytogenes and L. innocua, and all species possessed at least intermediate resistance to fluoroquinolones. GyrA, parC, and mprF were detected in all isolates; however, mutations were found only in gyrA sequences. A high daptomycin MIC, as reported previously, was observed, suggesting an intrinsic resistance of Listeria spp. to daptomycin. Conclusions: These results are consistent with reports of emerging resistance in Listeria spp. and emphasize the need for further genotypic characterization of antibiotic resistance in this genus.

scholarly journals The Mechanism of Action of Ginkgolic Acid (15:1) against Gram-Positive Bacteria Involves Cross Talk with Iron Homeostasis

2022 ◽  
Author(s):  
Zewen Wen ◽  
Yuxi Zhao ◽  
Zhengyang Gong ◽  
Yuanyuan Tang ◽  
Yanpeng Xiong ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Natural Product ◽  
Iron Homeostasis ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Ginkgolic Acid ◽  
Wide Range ◽  
Novel Antibiotics

The increasing emergence of infectious diseases associated with multidrug-resistant Gram-positive pathogens has raised the urgent need to develop novel antibiotics. GA (15:1) is a natural product derived from Ginkgo biloba and possesses a wide range of bioactivities, including antimicrobial activity.

scholarly journals Efficacy of Phage-Antibiotic Combinations Against Multidrug-Resistant Klebsiella pneumoniae Clinical Isolates

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hafiza Qurat-ul-Ain ◽  
Muhammad Ijaz ◽  
Abu Baker Siddique ◽  
Saima Muzammil ◽  
Muhammad Shafique ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Therapeutic Effects ◽  
Transmission Electron ◽  
Hospital Sewage ◽  
Therapeutic Alternatives ◽  
Overlay Assay

Background: Increasing antibiotic resistance warrants therapeutic alternatives to eradicate resistant bacteria. Combined phage-antibiotic therapy is a promising approach for eliminating bacterial infections and limiting the evolution of therapy-resistant diseases. Objectives: In the present study, we evaluated the effects of combinations of bacteriophages and antibiotics against multidrug-resistant (MDR) Klebsiella pneumoniae. Methods: Two MDR strains (GenBank no. MF953600 & MF953599) of K. pneumoniae were used. Bacteriophages were isolated from hospital sewage samples by employing a double agar overlay assay and identified by transmission electron microscopy. For further characterization of bacteriophages, the killing assay and host range test were performed. To assess therapeutic efficacy, phages (7.5 × 104 PFU/mL) were used in combination with various antibiotics. Results: The phage-cefepime & tetracycline combinations displayed promising therapeutic effects, restricting the growth of K. pneumoniae isolates, as evidenced by recording OD650nm values. Conclusions: The results of the current study showed that phage-antibiotic combination was a potential therapeutic approach to treat the infections caused by MDR K. pneumoniae.

MALAT1 as a Versatile Regulator of Cancer: Overview of the updates from Predatory role as Competitive Endogenous RNA to Mechanistic In-sights

2020 ◽  
Vol 20 ◽  
Author(s):  
Ammad Ahmad Farooqi ◽  
Evangelia Legaki ◽  
Maria Gazouli ◽  
Silvia Rinaldi ◽  
Rossana Berardi
Keyword(s):  
Molecular Biology ◽  
Detailed Analysis ◽  
Signaling Pathways ◽  
Individualized Medicine ◽  
Signaling Cascades ◽  
Oncogenic Signaling ◽  
Non Coding Rnas ◽  
Oncogenic Signaling Pathways ◽  
Competitive Endogenous Rna

: Central dogma of molecular biology has remained cornerstone of classical molecular biology but serendipitous discovery of microRNAs (miRNAs) in nematodes paradigmatically shifted our current understanding of the intricate mech-anisms which occur during transitions from transcription to translation. Discovery of miRNA captured tremendous attention and appreciation and we had witnessed an explosion in the field of non-coding RNAs. Ground-breaking discoveries in the field of non-coding RNAs have helped in better characterization of microRNAs and long non-coding RNAs (LncRNAs). There is an ever-increasing list of miRNA targets which are regulated by MALAT1 to stimulate or repress expression of tar-get genes. However, in this review our main focus is to summarize mechanistic insights related to MALAT1-mediated regu-lation of oncogenic signaling pathways. We have discussed how MALAT1 modulated TGF/SMAD and Hippo pathways in various cancers. We have also comprehensively summarized how JAK/STAT and Wnt/β-catenin pathways stimulated MALAT1 expression and consequentially how MALAT1 potentiated these signaling cascades to promote cancer. MALAT1 research has undergone substantial broadening however, there is still a need to identify additional mechanisms. MALAT1 is involved in multi-layered regulation of multiple transduction cascades and detailed analysis of different pathways will be helpful in getting a step closer to individualized medicine.

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