scholarly journals Structures of the CRISPR/Cas System in the Genome of the Staphylococcus aureus ST228 Strain and Phage Races Detected by Bioinformatics

2020 ◽  
Vol 31 ◽  
pp. 3-18
Author(s):  
A. Yu. Borisenko ◽  
◽  
Yu. P. Dzhioev ◽  
L. A. Stepanenko ◽  
Yu. M. Zemlyanskaya ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Strain ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Multidrug Resistant ◽  
Aureus Strain ◽  
Modern World ◽  
Bacterial Genomes ◽  
Alternative Antibiotic

In the modern world, infections caused by multidrug-resistant (MDR) bacteria have become carriers of global threats to human health. Today these pathogenic bacteria have come to be referred to as "superbugs" and their number and aggressiveness is growing. This group of "superbugs" also includes Staphylococcus aureus. It is capable of infecting almost any tissue in the human body. Therefore, it became necessary to find alternative antibiotic methods of treating bacterial infections. The use of bacteriophages is again among them. We propose a new approach in the search for strain-specific (target) phages through the structures of the CRISPR/Cas-systems of bacteria. As is known, CRISPR/Cas systems are the most ancient system of "adaptive immunity" in bacteria. This system makes bacteria resistant to phages and plasmids. This approach is based on the use of methods of structural genomics and software bioinformatics modeling. Using them, an algorithm was developed to search for the structures of CRISPR/Cas systems in bacterial genomes presented in the NCBI databases and screening through their CRISPR cassettes of phages with which a particular strain could meet. The design of the developed algorithm was tested on the genome of methicillin-resistant S. aureus strain (ST228-MRSA-I) from the GenBank database. The results of the search for loci and structures of the CRISPR/Cas system in the genome of this strain showed that the identified system belongs to type III-A. It was found that the cas genes and the CRISPR cassette are located at a distance from each other and between them are located several genes that perform other functions in the genome of the S. aureus strain. It was shown that the structures of spacers in the detected CRISPR cassette are identical to protospacers of phages, the hosts of which are bacteria of the following genera – Staphylococcus, Mycobacterium, Streptococcus, Bacillus, Gordonia, Arthrobacter, Streptomyces. Thus, it can be stated that the developed algorithm of software methods for searching for loci of CRISPR/Cas systems and screening for phages makes it possible to type both the system itself and through its spacers to detect and identify phage races with which a particular bacterial strain could meet. The degree of resistance of a particular bacterial strain to specific phages is also determined, which in the long term should ensure the effectiveness of targeted phage therapy for infections caused by pathogenic bacteria, including "superbugs".

scholarly journals Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria

2017 ◽  
Vol 63 (11) ◽  
pp. 865-879 ◽  
Author(s):  
Ayman El-Shibiny ◽  
Salma El-Sahhar
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Clinical Applications ◽  
Western World ◽  
Resistant Bacteria ◽  
Vaccine Production ◽  
Bacterial Populations ◽  
Antibiotic Resistant

Since their discovery in 1915, bacteriophages have been used to treat bacterial infections in animals and humans because of their unique ability to infect their specific bacterial hosts without affecting other bacterial populations. The research carried out in this field throughout the 20th century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulfonamide antibiotics in the Western World during the 1930s was a setback in the advancement of phage therapy. The misuse of antibiotics has reduced their efficacy in controlling pathogens and has led to an increase in the number of antibiotic-resistant bacteria. As an alternative to antibiotics, bacteriophages have become a topic of interest with the emergence of multidrug-resistant bacteria, which are a threat to public health. Recent studies have indicated that bacteriophages can be used indirectly to detect pathogenic bacteria or directly as biocontrol agents. Moreover, they can be used to develop new molecules for clinical applications, vaccine production, drug design, and in the nanomedicine field via phage display.

Intravenous Antibiotics Used in the Treatment of Methicillin-Resistant Staphylococcus Aureus

2015 ◽  
Vol 26 (3) ◽  
pp. 233-243
Author(s):  
Kristine Anne Scordo
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Medical Procedures ◽  
Term Care ◽  
Methicillin Resistant ◽  
Intravenous Antibiotics ◽  
Resistant Strains ◽  
Hospital Acquired

Methicillin-resistant Staphylococcus aureus (MRSA) continues to cause significant morbidity and mortality. Despite advances in medical care, the prevalence of both community-acquired and hospital-acquired MRSA has progressively increased. Community-acquired MRSA typically occurs in patients without recent illness or hospitalization, presents as acute skin and soft tissue infections, and is usually not multidrug resistant. Hospital-acquired MRSA, however, presents in patients recently hospitalized or treated in long-term care settings and in those who have had medical procedures and is usually associated with multidrug-resistant strains. Both types of infections, if not properly treated, have the potential to become invasive. This article discusses current intravenous antibiotics that are available for the empiric treatment of MRSA infections along with a newer phenomenon known as the “seesaw effect.”

scholarly journals Antimicrobial Resistance in Bacterial Pathogens and Detection of Carbapenemases in Klebsiella pneumoniae Isolates from Hospital Wastewater

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 85 ◽  
Author(s):  
Hercules Sakkas ◽  
Petros Bozidis ◽  
Afrodite Ilia ◽  
George Mpekoulis ◽  
Chrissanthy Papadopoulou
Keyword(s):  
Staphylococcus Aureus ◽  
Klebsiella Pneumoniae ◽  
Pathogenic Bacteria ◽  
Multidrug Resistant ◽  
Rapid Identification ◽  
Diffusion Method ◽  
Resistant Bacteria ◽  
Screening Methods ◽  
Extended Spectrum Beta Lactamase ◽  
Vancomycin Resistant

During a six-month period (October 2017–March 2018), the prevalence and susceptibility of important pathogenic bacteria isolated from 12 hospital raw sewage samples in North Western Greece was investigated. The samples were analyzed for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum beta-lactamase (ESBL) producing Escherichia coli, carbapenemase-producing Klebsiella pneumoniae (CKP), and multidrug-resistant Pseudomonas aeruginosa. Antimicrobial susceptibility testing was performed using the agar diffusion method according to the recommendations of the Clinical and Laboratory Standards Institute. The diversity of carbapenemases harboring K. pneumoniae was examined by two phenotyping screening methods (modified Hodge test and combined disk test), a new immunochromatographic rapid assay (RESIST-4 O.K.N.V.) and a polymerase chain reaction (PCR). The results demonstrated the prevalence of MRSA, vancomycin-resistant Staphylococcus aureus (VRSA), VRE, and CKP in the examined hospital raw sewage samples. In addition, the aforementioned methods which are currently used in clinical laboratories for the rapid identification and detection of resistant bacteria and genes, performed sufficiently to provide reliable results in terms of accuracy and efficiency.

scholarly journals Antimicrobial and Antifungal Activities of Terpene-Derived Palladium Complexes

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 277 ◽  
Author(s):  
Olga Zalevskaya ◽  
Yana Gur’eva ◽  
Aleksandr Kutchin ◽  
Karl A. Hansford
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Palladium Complexes ◽  
Antifungal Drugs ◽  
Antifungal Activities ◽  
Highly Active ◽  
Development Pipeline ◽  
Antimicrobial And Antifungal Activities ◽  
Global Health Problem

In an era of multidrug-resistant bacterial infections overshadowed by a lack of innovation in the antimicrobial drug development pipeline, there has been a resurgence in multidisciplinary approaches aimed at tackling this global health problem. One such approach is to use metal complexes as a framework for new antimicrobials. Indeed, in this context, bismuth-, silver- and gold-derived compounds in particular have displayed demonstrable antimicrobial activity. In this work, we discuss the antimicrobial and antifungal activities of terpene-derived chiral palladium complexes against Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Candida albicans, and Cryptococcus neoformans. It was established that all studied coordination compounds of palladium were highly active antifungal drugs. In contrast, the subset of palladacycles possessing a palladium–carbon bond were only active against the Gram-positive bacterium Staphylococcus aureus. All compounds were inactive against the Gram-negative bacteria tested.

scholarly journals α-Toxin is a mediator of Staphylococcus aureus–induced cell death and activates caspases via the intrinsic death pathway independently of death receptor signaling

2001 ◽  
Vol 155 (4) ◽  
pp. 637-648 ◽  
Author(s):  
Heike Bantel ◽  
Bhanu Sinha ◽  
Wolfram Domschke ◽  
Georg Peters ◽  
Klaus Schulze-Osthoff ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Death ◽  
Bacterial Infections ◽  
Death Receptor ◽  
Therapeutic Interventions ◽  
Aureus Strain ◽  
Death Domain ◽  
Caspase Activation ◽  
Cytochrome C Release ◽  
Intact Cells

Infections with Staphylococcus aureus, a common inducer of septic and toxic shock, often result in tissue damage and death of various cell types. Although S. aureus was suggested to induce apoptosis, the underlying signal transduction pathways remained elusive. We show that caspase activation and DNA fragmentation were induced not only when Jurkat T cells were infected with intact bacteria, but also after treatment with supernatants of various S. aureus strains. We also demonstrate that S. aureus–induced cell death and caspase activation were mediated by α-toxin, a major cytotoxin of S. aureus, since both events were abrogated by two different anti–α-toxin antibodies and could not be induced with supernatants of an α-toxin–deficient S. aureus strain. Furthermore, α-toxin–induced caspase activation in CD95-resistant Jurkat sublines lacking CD95, Fas-activated death domain, or caspase-8 but not in cells stably expressing the antiapoptotic protein Bcl-2. Together with our finding that α-toxin induces cytochrome c release in intact cells and, interestingly, also from isolated mitochondria in a Bcl-2-controlled manner, our results demonstrate that S. aureus α-toxin triggers caspase activation via the intrinsic death pathway independently of death receptors. Hence, our findings clearly define a signaling pathway used in S. aureus–induced cytotoxicity and may provide a molecular rationale for future therapeutic interventions in bacterial infections.

scholarly journals Effects of four antibiotics on the diversity of the intestinal microbiota

2021 ◽  
Author(s):  
Ce Huang ◽  
Shengyu Feng ◽  
Fengjiao Huo ◽  
Hailiang Liu
Keyword(s):  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Rrna Gene ◽  
Oral Antibiotics ◽  
Negative Effects ◽  
Pathogenic Potential ◽  
Intestinal Pathogens

ABSTRACTOral antibiotics remain the therapy of choice for severe bacterial infections; however, antibiotic use disrupts the intestinal microbiota, which increases the risk of colonization with intestinal pathogens. Currently, our understanding of antibiotic-mediated disturbances of the microbiota remains at the level of bacterial families or specific species, and little is known about the effect of antibiotics on potentially beneficial and potentially pathogenic bacteria under conditions of gut microbiota dysbiosis. Additionally, it is controversial whether the effects of antibiotics on the gut microbiota are temporary or permanent. In this study, we used 16S rRNA gene sequencing to evaluate the short-term and long-term effects of ampicillin, vancomycin, metronidazole, and neomycin on the murine intestinal microbiota by analyzing changes in the relative numbers of potentially beneficial and potentially pathogenic bacteria. We found that the changes in the intestinal microbiota reflected the antibiotics’ mechanisms of action and that dysbiosis of the intestinal microbiota led to competition between the different bacterial communities. Thus, destruction of bacteria with beneficial potential increased the abundance of bacteria with pathogenic potential. In addition, we found that these oral antibiotics had long-term negative effects on the intestinal microbiota and promoted the development of antibiotic-resistant bacterial strains. These results indicate that ampicillin, vancomycin, metronidazole, and neomycin have long-term negative effects and can cause irreversible changes in the diversity of the intestinal microbiota and the relative proportions of bacteria with beneficial potential and bacteria with pathogenic potential, thereby increasing the risk of host disease.

scholarly journals Methicillin-Resistant Staphylococcus aureus Clonal Types in the Czech Republic

1999 ◽  
Vol 37 (9) ◽  
pp. 2798-2803 ◽  
Author(s):  
O. Melter ◽  
I. Santos Sanches ◽  
J. Schindler ◽  
M. Aires de Sousa ◽  
R. Mato ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Czech Republic ◽  
Pathogenic Bacteria ◽  
Multidrug Resistant ◽  
Pfge Pattern ◽  
Type I ◽  
The Czech Republic ◽  
Methicillin Resistant ◽  
Almost All ◽  
Genotypic Characteristics

Molecular surveillance studies have documented the extensive spread of methicillin-resistant Staphylococcus aureus (MRSA) clones. Studies carried out by Centro de Epidemiologia Molecular-Network for Tracking Gram-Positive Pathogenic Bacteria (CEM/NET) led to the identification of two international multidrug-resistant strains, which were designated as the Iberian and Brazilian MRSA clones and which were defined by multiple genomic typing methods; these included ClaI restriction digests hybridized with mecA- and Tn554-specific DNA probes and pulsed-field gel electrophoresis (PFGE). The genotypic characteristics of these clones are distinct: the Iberian clone is defined asmecA type I, Tn554 type E (or its variants), and PFGE pattern A (I:E:A), whereas the Brazilian clone is defined asmecA type XI (or its variants), Tn554 type B, and PFGE pattern B (XI:B:B). In this study, we characterized 59 single-patient isolates of MRSA collected during 1996 and 1997 at seven hospitals located in Prague and five other cities in the Czech Republic by using the methodologies mentioned above and by using ribotyping ofEcoRI and HindIII digests hybridized with a 16S-23S DNA probe. The Brazilian MRSA clone (XI:B:B) was the major clone (80%) spread in two hospitals located in Prague and one located in Brno; the Iberian MRSA clone (I:E:A or its variant I:DD:A), although less representative (12%), was detected in two hospitals, one in Prague and the other in Plzen. Almost all the strains belonging to clone XI:B:B (45 of 47) corresponded to a unique ribotype, E1H1, whereas most strains of the I:E:A and I:DD:A clonal types (6 of 7) corresponded to ribotype E2H2.

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.

scholarly journals Resistance Evolution against Phage Combinations Depends on the Timing and Order of Exposure

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Rosanna C. T. Wright ◽  
Ville-Petri Friman ◽  
Margaret C. M. Smith ◽  
Michael A. Brockhurst
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Fitness Costs ◽  
Evolutionary Trajectory ◽  
Promising Alternative ◽  
Content Type ◽  
Resistance Evolution

ABSTRACTPhage therapy is a promising alternative to chemotherapeutic antibiotics for the treatment of bacterial infections. However, despite recent clinical uses of combinations of phages to treat multidrug-resistant infections, a mechanistic understanding of how bacteria evolve resistance against multiple phages is lacking, limiting our ability to deploy phage combinations optimally. Here, we show, usingPseudomonas aeruginosaand pairs of phages targeting shared or distinct surface receptors, that the timing and order of phage exposure determine the strength, cost, and mutational basis of resistance. Whereas sequential exposure allowed bacteria to acquire multiple resistance mutations effective against both phages, this evolutionary trajectory was prevented by simultaneous exposure, resulting in quantitatively weaker resistance. The order of phage exposure determined the fitness costs of sequential resistance, such that certain sequential orders imposed much higher fitness costs than the same phage pair in the reverse order. Together, these data suggest that phage combinations can be optimized to limit the strength of evolved resistances while maximizing their associated fitness costs to promote the long-term efficacy of phage therapy.IMPORTANCEGlobally rising rates of antibiotic resistance have renewed interest in phage therapy where combinations of phages have been successfully used to treat multidrug-resistant infections. To optimize phage therapy, we first need to understand how bacteria evolve resistance against combinations of multiple phages. Here, we use simple laboratory experiments and genome sequencing to show that the timing and order of phage exposure determine the strength, cost, and mutational basis of resistance evolution in the opportunistic pathogenPseudomonas aeruginosa. These findings suggest that phage combinations can be optimized to limit the emergence and persistence of resistance, thereby promoting the long-term usefulness of phage therapy.

scholarly journals Harnessing the Intriguing Properties of Magnetic Nanoparticles to Detect and Treat Bacterial Infections

2021 ◽  
Vol 7 (8) ◽  
pp. 112
Author(s):  
Lingchao Xiang ◽  
Ozioma Udochukwu Akakuru ◽  
Chen Xu ◽  
Aiguo Wu
Keyword(s):  
Public Health ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Bacterial Detection ◽  
Prevention And Treatment ◽  
Further Development

Infections caused by pathogenic bacteria, especially multidrug-resistant bacteria, have become a serious worldwide public health problem. Early diagnosis and treatment can effectively prevent the adverse effects of such infections. Therefore, there is an urgent need to develop effective methods for the early detection, prevention, and treatment of diseases that are caused by bacterial infections. So far, magnetic material nanoparticles (MNPs) have been widely used in the detection and treatment of bacterial infections as detection agents and therapeutics. Therefore, this review describes the recent research on MNPs in bacterial detection and treatment. Finally, a brief discussion of challenges and perspectives in this field is provided, which is expected to guide the further development of MNPs for bacterial detection and treatment.

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