scholarly journals Staphylococcus aureus TargetArray: Comprehensive Differential Essential Gene Expression as a Mechanistic Tool To Profile Antibacterials

2010 ◽  
Vol 54 (9) ◽  
pp. 3659-3670 ◽  
Author(s):  
H. Howard Xu ◽  
John D. Trawick ◽  
Robert J. Haselbeck ◽  
R. Allyn Forsyth ◽  
Robert T. Yamamoto ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Essential Gene ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Cellular Targets ◽  
Comprehensive Method ◽  
Antibiotic Drug ◽  
Fitness Tests ◽  
Regulatable Promoters ◽  
Antibiotic Discovery

ABSTRACT The widespread emergence of antibiotic-resistant bacteria and a lack of new pharmaceutical development have catalyzed a need for new and innovative approaches for antibiotic drug discovery. One bottleneck in antibiotic discovery is the lack of a rapid and comprehensive method to identify compound mode of action (MOA). Since a hallmark of antibiotic action is as an inhibitor of essential cellular targets and processes, we identify a set of 308 essential genes in the clinically important pathogen Staphylococcus aureus. A total of 446 strains differentially expressing these genes were constructed in a comprehensive platform of sensitized and resistant strains. A subset of strains allows either target underexpression or target overexpression by heterologous promoter replacements with a suite of tetracycline-regulatable promoters. A further subset of 236 antisense RNA-expressing clones allows knockdown expression of cognate targets. Knockdown expression confers selective antibiotic hypersensitivity, while target overexpression confers resistance. The antisense strains were configured into a TargetArray in which pools of sensitized strains were challenged in fitness tests. A rapid detection method measures strain responses toward antibiotics. The TargetArray antibiotic fitness test results show mechanistically informative biological fingerprints that allow MOA elucidation.

scholarly journals Review on the Antibacterial Mechanism of Plant-Derived Compounds against Multidrug-Resistant Bacteria (MDR)

2021 ◽  
Vol 2021 ◽  
pp. 1-30
Author(s):  
Najwan Jubair ◽  
Mogana Rajagopal ◽  
Sasikala Chinnappan ◽  
Norhayati Binti Abdullah ◽  
Ayesha Fatima
Keyword(s):  
Secondary Metabolites ◽  
Plant Secondary Metabolites ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Resistance Strategies ◽  
Microbial Infections ◽  
Ancient Times ◽  
Antibiotic Discovery

Microbial resistance has progressed rapidly and is becoming the leading cause of death globally. The spread of antibiotic-resistant microorganisms has been a significant threat to the successful therapy against microbial infections. Scientists have become more concerned about the possibility of a return to the pre-antibiotic era. Thus, searching for alternatives to fight microorganisms has become a necessity. Some bacteria are naturally resistant to antibiotics, while others acquire resistance mainly by the misuse of antibiotics and the emergence of new resistant variants through mutation. Since ancient times, plants represent the leading source of drugs and alternative medicine for fighting against diseases. Plants are rich sources of valuable secondary metabolites, such as alkaloids, quinones, tannins, terpenoids, flavonoids, and polyphenols. Many studies focus on plant secondary metabolites as a potential source for antibiotic discovery. They have the required structural properties and can act by different mechanisms. This review analyses the antibiotic resistance strategies produced by multidrug-resistant bacteria and explores the phytochemicals from different classes with documented antimicrobial action against resistant bacteria, either alone or in combination with traditional antibiotics.

scholarly journals Hypochlorite-Activated Fluorescence Emission and Antibacterial Activities of Imidazole Derivatives for Biological Applications

2021 ◽  
Vol 9 ◽  
Author(s):  
Thanh Chung Pham ◽  
Van-Nghia Nguyen ◽  
Yeonghwan Choi ◽  
Dongwon Kim ◽  
Ok-Sang Jung ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Stokes Shift ◽  
Fluorescence Emission ◽  
Antibacterial Activities ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Fluorogenic Probe ◽  
High Fluorescence

The ability to detect hypochlorite (HOCl/ClO−) in vivo is of great importance to identify and visualize infection. Here, we report the use of imidazoline-2-thione (R1SR2) probes, which act to both sense ClO− and kill bacteria. The N2C=S moieties can recognize ClO− among various typical reactive oxygen species (ROS) and turn into imidazolium moieties (R1IR2) via desulfurization. This was observed through UV–vis absorption and fluorescence emission spectroscopy, with a high fluorescence emission quantum yield (ՓF = 43–99%) and large Stokes shift (∆v∼115 nm). Furthermore, the DIM probe, which was prepared by treating the DSM probe with ClO−, also displayed antibacterial efficacy toward not only Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) but also methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum ß-lactamase–producing Escherichia coli (ESBL-EC), that is, antibiotic-resistant bacteria. These results suggest that the DSM probe has great potential to carry out the dual roles of a fluorogenic probe and killer of bacteria.

scholarly journals Thinking Outside the Bug: Molecular Targets and Strategies to Overcome Antibiotic Resistance

2019 ◽  
Vol 20 (6) ◽  
pp. 1255 ◽  
Author(s):  
Ana Monserrat-Martinez ◽  
Yann Gambin ◽  
Emma Sierecki
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Rational Design ◽  
Disease Onset ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
New Antibiotics ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Antibiotic Discovery

Since their discovery in the early 20th century, antibiotics have been used as the primary weapon against bacterial infections. Due to their prophylactic effect, they are also used as part of the cocktail of drugs given to treat complex diseases such as cancer or during surgery, in order to prevent infection. This has resulted in a decrease of mortality from infectious diseases and an increase in life expectancy in the last 100 years. However, as a consequence of administering antibiotics broadly to the population and sometimes misusing them, antibiotic-resistant bacteria have appeared. The emergence of resistant strains is a global health threat to humanity. Highly-resistant bacteria like Staphylococcus aureus (methicillin-resistant) or Enterococcus faecium (vancomycin-resistant) have led to complications in intensive care units, increasing medical costs and putting patient lives at risk. The appearance of these resistant strains together with the difficulty in finding new antimicrobials has alarmed the scientific community. Most of the strategies currently employed to develop new antibiotics point towards novel approaches for drug design based on prodrugs or rational design of new molecules. However, targeting crucial bacterial processes by these means will keep creating evolutionary pressure towards drug resistance. In this review, we discuss antibiotic resistance and new options for antibiotic discovery, focusing in particular on new alternatives aiming to disarm the bacteria or empower the host to avoid disease onset.

Something old, something new: revisiting natural products in antibiotic drug discovery

2014 ◽  
Vol 60 (3) ◽  
pp. 147-154 ◽  
Author(s):  
Gerard D. Wright
Keyword(s):  
Natural Products ◽  
New Drugs ◽  
Clinical Use ◽  
Antibiotic Resistant ◽  
Antibiotic Drug ◽  
New Antibiotics ◽  
Bacteria And Fungi ◽  
Antibiotic Discovery ◽  
Novel Drug ◽  
New Strategies

Antibiotic discovery is in crisis. Despite a growing need for new drugs resulting from the increasing number of multi-antibiotic-resistant pathogens, there have been only a handful of new antibiotics approved for clinical use in the past 2 decades. Faced with scientific, economic, and regulatory challenges, the pharmaceutical sector seems unable to respond to what has been called an “apocalyptic” threat. Natural products produced by bacteria and fungi are genetically encoded products of natural selection that have been the mainstay sources of the antibiotics in current clinical use. The pharmaceutical industry has largely abandoned these compounds in favor of large libraries of synthetic molecules because of difficulties in identifying new natural product antibiotics scaffolds. Advances in next-generation genome sequencing, bioinformatics, and analytical chemistry are combining to overcome barriers to natural products. Coupled with new strategies in antibiotic discovery, including inhibition of resistance, novel drug combinations, and new targets, natural products are poised for a renaissance to address what is a pressing health care crisis.

scholarly journals Development of a Novel Chimeric Endolysin, Lys109 With Enhanced Lytic Activity Against Staphylococcus aureus

2021 ◽  
Vol 11 ◽  
Author(s):  
Bokyung Son ◽  
Minsuk Kong ◽  
Yoona Lee ◽  
Sangryeol Ryu
Keyword(s):  
Staphylococcus Aureus ◽  
Stainless Steel ◽  
Lytic Activity ◽  
Domain Swapping ◽  
Soluble Form ◽  
Resistant Bacteria ◽  
The Novel ◽  
Planktonic Cells ◽  
Antibiotic Resistant ◽  
Modular Structures

As the incidence of antibiotic-resistant bacteria has become increased, phage endolysins are believed as one of the promising alternatives to antibiotics. However, the discovery of potent endolysin is still challenging because it is labor intensive and difficult to obtain a soluble form with high lytic activity. In this respect, the modular structures of Gram-positive endolysins can provide an opportunity to develop novel endolysins by domain rearrangement. In this study, a random domain swapping library of four different endolysins from phages infecting Staphylococcus aureus was constructed and screened to obtain engineered endolysins. The novel chimeric endolysin, Lys109 was selected and characterized for its staphylolytic activity. Lys109 exhibited greater bacterial cell lytic activity than its parental endolysins against staphylococcal planktonic cells and biofilms, showing highly improved activity in eliminating S. aureus from milk and on the surface of stainless steel. These results demonstrate that a novel chimeric endolysin with higher activity and solubility can be developed by random domain swapping and that this chimeric endolysin has a great potential as an antimicrobial agent.

scholarly journals Identification and characterization of vancomycin-resistant Staphylococcus aureus in hospital wastewaters: evidence of horizontal spread of antimicrobial resistance

2021 ◽  
Author(s):  
Sneha Kalasseril Girijan ◽  
Devika Pillai
Keyword(s):  
Staphylococcus Aureus ◽  
Aquatic Environment ◽  
Water Bodies ◽  
Resistant Bacteria ◽  
Hospital Discharges ◽  
Antibiotic Resistant ◽  
Vana Gene ◽  
Vancomycin Resistant ◽  
Horizontal Spread ◽  
Hospital Wastewaters

Abstract Antibiotic resistance has become a major threat to human health around the world, but its spread through the aquatic environment has been often overlooked. This study aimed to determine the occurrence of vancomycin-resistant Staphylococcus aureus in hospital wastewaters and their transmission into public water bodies in Kerala, India. A total of 113 S. aureus were isolated from three hospital effluents in Kerala, India. Standard disc diffusion and the strip method were used for antibiotic susceptibility testing and minimum inhibitory concentration detection. Plasmid-mediated vancomycin resistance was confirmed by plasmid curing and conjugation; resistant genes were detected by the polymerase chain reaction (PCR). Nearly 76% of S. aureus isolates were resistant to β-lactams, chloramphenicol, macrolides, aminoglycosides, and glycopeptide class of antibiotics. Among the vancomycin-resistant Staphylococcus aureus (VRSA) isolates, the prevalence rates of vanA and vanB resistance-encoding genes were 46.5 and 59.3%, respectively. Through the broth mating method, vanA gene was successfully transferred from VRSA donor to vancomycin-sensitive S. aureus. The study strongly indicates the contamination of water bodies with antibiotic-resistant bacteria from hospital discharges, their dissemination and possible transfer to microbes in the aquatic environment, posing a serious threat for public health.

scholarly journals Drug-resistant Staphylococcus aureus bacteria detection by combining surface-enhanced Raman spectroscopy (SERS) and deep learning techniques

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fatma Uysal Ciloglu ◽  
Abdullah Caliskan ◽  
Ayse Mine Saridag ◽  
Ibrahim Halil Kilic ◽  
Mahmut Tokmakci ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Raman Spectroscopy ◽  
Deep Learning ◽  
Surface Enhanced Raman Spectroscopy ◽  
Resistant Bacteria ◽  
High Signal ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Surface Enhanced ◽  
Surface Enhanced Raman

AbstractOver the past year, the world's attention has focused on combating COVID-19 disease, but the other threat waiting at the door—antimicrobial resistance should not be forgotten. Although making the diagnosis rapidly and accurately is crucial in preventing antibiotic resistance development, bacterial identification techniques include some challenging processes. To address this challenge, we proposed a deep neural network (DNN) that can discriminate antibiotic-resistant bacteria using surface-enhanced Raman spectroscopy (SERS). Stacked autoencoder (SAE)-based DNN was used for the rapid identification of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) bacteria using a label-free SERS technique. The performance of the DNN was compared with traditional classifiers. Since the SERS technique provides high signal-to-noise ratio (SNR) data, some subtle differences were found between MRSA and MSSA in relative band intensities. SAE-based DNN can learn features from raw data and classify them with an accuracy of 97.66%. Moreover, the model discriminates bacteria with an area under curve (AUC) of 0.99. Compared to traditional classifiers, SAE-based DNN was found superior in accuracy and AUC values. The obtained results are also supported by statistical analysis. These results demonstrate that deep learning has great potential to characterize and detect antibiotic-resistant bacteria by using SERS spectral data.

scholarly journals Design, Overproduction and Purification of the Chimeric Phage Lysin MLTphg Fighting against Staphylococcus aureus

Processes ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 1587
Author(s):  
Feng Wang ◽  
Xiaohang Liu ◽  
Zhengyu Deng ◽  
Yao Zhang ◽  
Xinyu Ji ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Conventional Antibiotics ◽  
Phage Lysin ◽  
Shed Light

With the increasing spread of multidrug-resistant bacterial pathogens, it is of great importance to develop alternatives to conventional antibiotics. Here, we report the generation of a chimeric phage lysin, MLTphg, which was assembled by joining the lysins derived from Meiothermus bacteriophage MMP7 and Thermus bacteriophage TSP4 with a flexible linker via chimeolysin engineering. As a potential antimicrobial agent, MLTphg can be obtained by overproduction in Escherichia coli BL21(DE3) cells and the following Ni-affinity chromatography. Finally, we recovered about 40 ± 1.9 mg of MLTphg from 1 L of the host E. coli BL21(DE3) culture. The purified MLTphg showed peak activity against Staphylococcus aureus ATCC6538 between 35 and 40 °C, and maintained approximately 44.5 ± 2.1% activity at room temperature (25 °C). Moreover, as a produced chimera, it exhibited considerably improved bactericidal activity against Staphylococcus aureus (2.9 ± 0.1 log10 reduction was observed upon 40 nM MLTphg treatment at 37 °C for 30 min) and also a group of antibiotic-resistant bacteria compared to its parental lysins, TSPphg and MMPphg. In the current age of growing antibiotic resistance, our results provide an engineering basis for developing phage lysins as novel antimicrobial agents and shed light on bacteriophage-based strategies to tackle bacterial infections.

Sign in / Sign up

Export Citation Format

Share Document