scholarly journals Characterization of Salmonella Isolates from Various Geographical Regions of the Caucasus and Their Susceptibility to Bacteriophages

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1418
Author(s):  
Khatuna Makalatia ◽  
Elene Kakabadze ◽  
Jeroen Wagemans ◽  
Nino Grdzelishvili ◽  
Nata Bakuradze ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Therapeutic Potential ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Additional Tool ◽  
Food Borne ◽  
Microbiological Methods ◽  
Geographical Regions ◽  
Susceptibility Profiles

Non-typhoidal Salmonella present a major threat to animal and human health as food-borne infectious agents. We characterized 91 bacterial isolates from Armenia and Georgia in detail, using a suite of assays including conventional microbiological methods, determining antimicrobial susceptibility profiles, matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry, serotyping (using the White-Kauffmann-Le Minor scheme) and genotyping (repetitive element sequence-based PCR (rep-PCR)). No less than 61.5% of the isolates were shown to be multidrug-resistant. A new antimicrobial treatment strategy is urgently needed. Phage therapy, the therapeutic use of (bacterio-) phages, the bacterial viruses, to treat bacterial infections, is increasingly put forward as an additional tool for combatting antibiotic resistant infections. Therefore, we used this representative set of well-characterized Salmonella isolates to analyze the therapeutic potential of eleven single phages and selected phage cocktails from the bacteriophage collection of the Eliava Institute (Georgia). All isolates were shown to be susceptible to at least one of the tested phage clones or their combinations. In addition, genome sequencing of these phages revealed them as members of existing phage genera (Felixounavirus, Seunavirus, Viunavirus and Tequintavirus) and did not show genome-based counter indications towards their applicability against non-typhoidal Salmonella in a phage therapy or in an agro-food setting.

scholarly journals Isolation and Study of Bacteriophages Specific Against Multidrug Resistant Salmonella spp. and Assessment of their Therapeutic Potential

2021 ◽  
Author(s):  
Khatuna Makalatia ◽  
Elene Kakabadze ◽  
Nino Grdzelishvili ◽  
Nata Bakuradze ◽  
Nino Chanishvili
Keyword(s):  
Therapeutic Potential ◽  
Multidrug Resistant ◽  
In Vitro Tests ◽  
Salmonella Spp ◽  
Clinical Strains ◽  
Additional Tool ◽  
Salmonella Infections ◽  
Microbiological Methods ◽  
Genetic Features

Within the scope of the study, clinical non-typhoidal Salmonella were isolated in Armenia and Georgia and identified based on conventional microbiological methods and MALDI-TOF MS. These isolates were further analysed by serotyping (White-Kauffmann-Le Minor scheme) and their antimicrobial susceptibility profiles were defined. A total of 40 antibiotic resistance profiles were identified, of which 35 were characteristic of clinical strains. Out of a total of 345 isolates, 238 strains from Georgia, Armenia and Ireland were eventually selected for our study.Using the strains of this collection, 13 new bacteriophages were isolated, characterized by biological and genetic features. Based on the data obtained, phages were classified and the peculiarities of their life cycle were determined (virulent-lytic, moderate-lysogenic).Analysis of the sequencing results showed that only one of the 12 phages identified as temperate phage (vB_GEC_ TR), it belongs to the family Podoviridae, genus-Laderbergvirus. While the other 11 phages are virulent, they are related to well-known and characterized phages, which are used in various phage preparations. Analysis of their genomes did not show any lysogeny associated genes. Among the virulent phages, 6 are members of Myoviridae family (vB_GEC_B1, vB_GEC_B3, vB_GEC_MG, vB_GEC_BS, vB_GEC_NS7, vB_GEC_7A) and 5 of the Syphoviridae family (vB_GEC_N5, vB_GEC_N8, vB_GEC_M4, vB_GEC_M5, vB_GEC_Hi). In vitro tests revealed that the phages - vB_GEC_B1, vB_GEC_BS, vB_GEC_B3, vB_GEC_NS7, vB-GEC-N8 showed high activity (60% to 80%) against the examined strains. The phages have been shown to be more effective against clinical strains (≈90%) than against veterinary strains (≈70%). The strains susceptible to these phages were mainly S.typhimurium and S. Enteritidis serovars and are largely of clinical origin. Based on our research we can conclude that the application of phages as an additional tool for the treatment of MDR Salmonella infections seems to be plausible. Phages are natural and specific antibacterial agents, which can lyse bacteria.irrespective of their AMR status, whilst leaving the commensal microflora unharmed. This is one of the main advantages of phages in comparison to antibiotics. The phages tested in this study showed potential for application in phage therapy against MDR Salmonella infections.

scholarly journals Low Immunogenicity of Intravesical Phage Therapy for Urogenitary Tract Infections

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 627
Author(s):  
Sławomir Letkiewicz ◽  
Marzanna Łusiak-Szelachowska ◽  
Ryszard Międzybrodzki ◽  
Maciej Żaczek ◽  
Beata Weber-Dąbrowska ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Serum Antibody ◽  
Multidrug Resistant ◽  
Antibody Responses ◽  
Urogenital Infections ◽  
Reliable Model ◽  
Tract Infections ◽  
Antibody Levels

Patients with chronic urinary and urogenital multidrug resistant bacterial infections received phage therapy (PT) using intravesical or intravesical and intravaginal phage administration. A single course of PT did not induce significant serum antibody responses against administered phage. Whilst the second cycle of PT caused a significant increase in antibody levels, they nevertheless remained quite low. These data combined with good therapy results achieved in some patients suggest that this mode of PT may be an efficient means of therapy for urogenital infections and a reliable model for a clinical trial of PT.

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.

scholarly journals Engineered Lysins With Customized Lytic Activities Against Enterococci and Staphylococci

2020 ◽  
Vol 11 ◽  
Author(s):  
Hana Sakina Binte Muhammad Jai ◽  
Linh Chi Dam ◽  
Lowella Servito Tay ◽  
Jodi Jia Wei Koh ◽  
Hooi Linn Loo ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Catalytic Domain ◽  
Therapeutic Potential ◽  
Multidrug Resistant ◽  
Species Specificity ◽  
Resistant Bacteria ◽  
Modular Architecture ◽  
Narrow Spectrum ◽  
Cell Wall Binding ◽  
Peptidoglycan Hydrolysis

The emergence of multidrug-resistant bacteria has made minor bacterial infections incurable with many existing antibiotics. Lysins are phage-encoded peptidoglycan hydrolases that have demonstrated therapeutic potential as a novel class of antimicrobials. The modular architecture of lysins enables the functional domains – catalytic domain (CD) and cell wall binding domain (CBD) – to be shuffled to create novel lysins. The CD is classically thought to be only involved in peptidoglycan hydrolysis whereas the CBD dictates the lytic spectrum of a lysin. While there are many studies that extended the lytic spectrum of a lysin by domain swapping, few have managed to introduce species specificity in a chimeric lysin. In this work, we constructed two chimeric lysins by swapping the CBDs of two parent lysins with different lytic spectra against enterococci and staphylococci. We showed that these chimeric lysins exhibited customized lytic spectra distinct from the parent lysins. Notably, the chimeric lysin P10N-V12C, which comprises a narrow-spectrum CD fused with a broad-spectrum CBD, displayed species specificity not lysing Enterococcus faecium while targeting Enterococcus faecalis and staphylococci. Such species specificity can be attributed to the narrow-spectrum CD of the chimeric lysin. Using flow cytometry and confocal microscopy, we found that the E. faecium cells that were treated with P10N-V12C are less viable with compromised membranes yet remained morphologically intact. Our results suggest that while the CBD is a major determinant of the lytic spectrum of a lysin, the CD is also responsible in the composition of the final lytic spectrum, especially when it pertains to species-specificity.

scholarly journals The Burden of the Serious and Difficult-to-Treat Infections and a New Antibiotic Available: Cefiderocol

2021 ◽  
Vol 11 ◽  
Author(s):  
Yasaman Taheri ◽  
Nataša Joković ◽  
Jelena Vitorović ◽  
Oliver Grundmann ◽  
Alfred Maroyi ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Antimicrobial Treatment ◽  
Bacterial Cells ◽  
Gram Negative ◽  
Pubmed Database ◽  
Severe Infections ◽  
Unique Cell

Background: Infection is a disease that can occur due to the entrance of a virus, bacteria, and other infectious agents. Cefiderocol is innovative cephalosporin drug that belongs to a special class of antibiotics, sideromycins, which are taken up by bacterial cells through active transport. The unique cell entry and stability to β-lactamases allow cefiderocol to overcome the most common resistance mechanisms in Gram-negative bacteria.Objective: This article aims to highlight the therapeutic efficacy, safety and tolerability of cefiderocol, with a focus on the FDA label.Methods: The pharmacological properties of cefiderocol are also summarized. In this review, we conducted literature research on the PubMed database using the following keywords: “antimicrobial treatment”, “new antibiotic”, “cefiderocol”, “siderophore cephalosporin”; “multidrug-resistant”, “Gram-negative bacilli”, “critically ill patients”; “severe bacterial infections”.Results: There were identified the most relevant data about the pathophysiology of serious bacterial infections, antibacterial mechanism of action, microbiology, mechanisms of resistance, pharmacokinetic and pharmacodynamic properties of cefiderocol.Conclusion: The results highlighted there appeared to be clinical benefit from cefiderocol in the treatment of infections caused by Gram-negative aerobic microorganisms in adult patients with severe infections and limited treatment options.

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 Antimicrobial Susceptibility Profiles and Molecular Typing of Campylobacter jejuni and Campylobacter coli Isolates from Ducks in South Korea

2014 ◽  
Vol 80 (24) ◽  
pp. 7604-7610 ◽  
Author(s):  
Bai Wei ◽  
Se-Yeoun Cha ◽  
Min Kang ◽  
Jae-Hee Roh ◽  
Hye-Suk Seo ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Multidrug Resistant ◽  
Human Infection ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Campylobacter Coli ◽  
Content Type ◽  
Food Borne ◽  
Production Animals ◽  
Susceptibility Profiles

ABSTRACTCampylobacteris a food-borne zoonotic pathogen that causes human gastroenteritis worldwide.Campylobacterbacteria are commensal in the intestines of many food production animals, including ducks and chickens. The objective of the study was to determine the prevalence ofCampylobacterspecies in domestic ducks, and the agar dilution method was used to determine resistance of the isolates to eight antibiotics. In addition, multilocus sequence typing (MLST) was performed to determine the sequence types (STs) of selectedCampylobacterisolates. Between May and September 2012, 58 duck farms were analyzed, and 56 (96.6%) were positive forCampylobacter. Among the isolates, 82.1% wereCampylobacter jejuni, 16.1% wereC. coli, and one was unidentified by PCR. Of the 46C. jejuniisolates, 87.0%, 10.9%, and 21.7% were resistant to ciprofloxacin, erythromycin, and azithromycin, respectively. Among theC. coliisolates, all 9 strains were resistant to ampicillin, and 77.8% and 33.3% were resistant to ciprofloxacin and azithromycin, respectively. The majority of theCampylobacterisolates were classified as multidrug resistant. Twenty-eight STs were identified, including 20 STs forC. jejuniand 8 STs forC. coli. The most common clonal complexes inC. jejuniwere the ST-21 complex and the ST-45 complex, while the ST-828 complex predominated inC. coli. The majority of isolates were of STs noted in ducks and humans from earlier studies, along with seven STs previously associated only with human disease. These STs overlapped between duck and human isolates, indicating thatCampylobacterisolates from ducks should be considered potential sources of human infection.

scholarly journals Molecular characterization of a multidrug-resistant/pandrug-resistant nosocomial polymicrobial infection with Klebsiella pneumoniae, Providencia rettgeri, and Acinetobacter baumannii from Rural Maharashtra, India

2020 ◽  
Author(s):  
Dilip D Karad ◽  
Yogesh Somani ◽  
Hemant Khande ◽  
Bipin Yadav ◽  
Arun S Kharat
Keyword(s):  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Molecular Characterization ◽  
Bacterial Infections ◽  
Rapid Development ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Polymicrobial Infection ◽  
Multiple Drug ◽  
Providencia Rettgeri

The emergence of resistance against commonly used antibiotics has become a serious global concern. The rapid development of antibiotic resistance exhibited by Enterobacteriaceae has caused an increasing concern regarding untreatable bacterial infections. Here, we isolated four pathogens from a geriatric female patient who was hospitalized for a month with ventilator-associated pneumonia (VAP) and fever. The organisms isolated from the tracheal aspirates and urine included Klebsiella pneumoniae, pandrug-resistant Providencia rettgeri, and Acinetobacter baumannii. Resistome analysis indicated that the bacterial isolates from the polymicrobial infection were multiple-drug resitnat and pandrug resistant clones. Molecular characterization revealed presence of blaTEM-1 in K. pneumonaie, P. rettgeri and A. baumannii. The blaTEM-1 and blaNDM-1 genes were present in P. rettgeri and A. baumannii, whereas the blaTEM-1, blaNDM-1 and blaOXA-23 traits were present in A. baumannii isolates. The patient has died due to the unavailability of effective antimicrobial treatment for this drug-resistant polymicrobial infection.  

scholarly journals Study of rapport of the milk pollution by multidrug-resistant bacteria (‘superbugs’), cows morbidity and calves lethality in holdings of eastern Ukraine

2019 ◽  
Vol 5 (1) ◽  
pp. 13-16
Author(s):  
O. V. Kolchyk ◽  
O. M. Korneikov ◽  
I. A. Bobrovytska
Keyword(s):  
Clostridium Perfringens ◽  
Bacterial Infections ◽  
Pasteurella Multocida ◽  
Clinical Signs ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Mycoplasma Bovis ◽  
Human Pathogens ◽  
Microbiological Methods

Pasteurella multocida (46.0%), Neisseria spp. (44.0%), Aspergillus fumigatus (10.0%) were isolated in stable consortia form from milk samples (n = 60) from cows in 6 herds (n = 627 heads) with clinical signs of immunodeficiency status. The bacteria of these consortia is strong resistant to lots of antibiotics from synthetic penicillin group (ampiox, amoxiclav, ampicillinum), cephalosporins (cefalexin, cefixime), and macrolides (macropene, tylosin). The etiological structure of bacterial infections in cattle and their calves (n = 57) in mentioned farm holdings of eastern Ukraine was determined (6 farms in 3 regions). In the majority of these livestock, respiratory syndrome has been recorded for a long time in 56.0% of calves from 20 days to 5 months old. The signs of diarrhea were revealed in 12.0% of lactating and dry cows of these livestock, 18.0% of these animals showed the clinical manifestation of mastitis and 9.0% of them had the diarrhea syndrome. Pasteurella multocida (48.0%), Mycoplasma bovis (32.0%), Neisseria spp. (12.0%), Clostridium perfringens (8.0%) were identified using microbiological methods from nasal and rectal swabs from calves of different age groups, from cows with clinical signs of mastitis were isolated Mycoplasma bovis (50.0%), Pasteurella multocida (34.0%), Neisseria spp. (16.0%). Pasteurella multocida, Neisseria spp. and Clostridium perfringens isolates showed strong resistance to ampiox, amoxiclav, ampicillinum, cefalexin, cefixime, macropene, and tylosin. It was concluded that mentioned multidrug-resistant animal infectious agents in human food chain could be a sources of antibiotic resistance genes for human pathogens.

scholarly journals Haemolysin and Shigella Toxin Production in Multidrug Resistant Escherichia Coli Pathotypes from Clinical Specimens

2021 ◽  
Vol 6 (1) ◽  
pp. 1-9
Author(s):  
Iliyasu MY
Keyword(s):  
Drug Resistance ◽  
Bacterial Infections ◽  
Virulence Genes ◽  
Strong Relationship ◽  
Toxin Production ◽  
Multidrug Resistant ◽  
Luria Bertani ◽  
Antimicrobial Treatment ◽  
Diffusion Method ◽  
E Coli

The acquisition and dissemination of virulent traits represent a survival advantage to bacterial pathogens. Drug resistance is on the rise among E. coli strains that cause human infections. Proper selection of antimicrobial treatment depends on the susceptibility test outcomes. A total of 178 bacterial isolates were phenotypically screened for Haemolysin and Shigatoxin production, then to obtain Multidrug Resistant (MDR) E. coli . Twelve isolates were identified and selected based on the ability to grow on Luria-Bertani (LB) agar medium containing 100μg/ml Ampicillin. The isolates, coded as; U01, U02, U03, U04, U08, U10 and U11 were from urine specimens, S05, S06, S07 and S12 from stool, while B09 was from blood. The isolates were screened for multidrug resistant pattern according to Kirby-Bauer disc diffusion method. Genes hlyA and stx1 encoding the virulence factors; Haemolysin A and Shigatoxin1 was PCR amplified and sequenced. All the isolates were resistant to Ampicillin, Cephalothin, Erythromycin, Fusidic acid, Novobiocin and Oxacillin, but sensitive to Colistin sulphate and Imipenem. Nine isolates (75%) are sensitive to Augmentin. All the virulence genes ( hlyA and stx1 ) are present in isolates S07 and U08. The isolates (75%) produced 2 to 4 of each of the genes indicating a strong relationship in determining multidrug resistance. Haemolysin ( hlyA ) was the most common (66.7%) gene in urine, stool and blood isolates. Most of the virulence genes sequence (61.8%) in this study had significant alignment (95 to 100% homology) with E.coli genome in the NCBI database. This study revealed the interplay of drug resistance and virulence at genetic levels, so advocate for further identification of the mechanisms regulating the expression of these traits, to improve the management of bacterial infections.

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