Bacteriophage infection drives loss of β-lactam resistance in methicillin-resistant Staphylococcus aureus DOI Open Access

My Tran,

Angel J Hernandez Viera, Patricia Q. Tran

et al.

Published: Oct. 25, 2024

Bacteriophage (phage) therapy has been proposed as a means to combat drug-resistant bacterial pathogens. Infection by phage can select for mutations in populations that confer resistance against infection. However, yield evolutionary trade-offs of biomedical use. Here we report the discovery staphylococcal phages cause different strains methicillin-resistant Staphylococcus aureus (MRSA) become sensitized β-lactams, class antibiotics which MRSA is typically highly resistant. cells survive infection these display significant reductions minimal inhibitory concentration β-lactams compared uninfected bacteria. Phage-treated further exhibited attenuated virulence phenotypes form reduced hemolysis and clumping. Sequencing analysis revealed evolved unique genetic profiles during These results suggest complex trajectories predation open up new possibilities reduce drug infections.

Language: Английский

Characterization of Twelve Erwinia amylovora Bacteriophages DOI Creative Commons
Natalya V. Besarab,

Andrei V. Letarov,

Ilya S. Belalov

et al.

Microbiology, Journal Year: 2024, Volume and Issue: 93(5), P. 666 - 685

Published: Sept. 30, 2024

Language: Английский

Citations

3
Structure and host specificity of Staphylococcus epidermidis bacteriophage Andhra DOI Creative Commons

N’Toia C. Hawkins,

James L. Kizziah, Asma Hatoum-Aslan

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(48)

Published: Nov. 30, 2022

Staphylococcus epidermidis is an opportunistic pathogen of the human skin, often associated with infections implanted medical devices. Staphylococcal picoviruses are a group strictly lytic, short-tailed bacteriophages compact genomes that attractive candidates for therapeutic use. Here, we report structure complete virion S. –infecting phage Andhra, determined using high-resolution cryo–electron microscopy, allowing atomic modeling 11 capsid and tail proteins. The T = 4 icosahedron containing unique stabilizing lining protein. includes 12 trimers receptor binding protein (RBP), lytic also serves to anchor RBPs stem, hexameric knob acts as gatekeeper DNA ejection. Using prediction AlphaFold, identified two proteins comprise tip heterooctamer. Our findings elucidate critical features assembly, host recognition, penetration.

Language: Английский

Citations

16
Wild-type Lactococcus lactis producing bacteriocin-like prophage lysins DOI Creative Commons
Timo M. Takala, Samira Mokhtari,

Susanna L. Ahonen

et al.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: July 14, 2023

Lactococcus is a genus of lactic acid bacteria used in the dairy industry as starter. Lactococci have been found to produce altogether more than 40 different bacteriocins, ribosomally synthesized antimicrobial proteins. All known spp. bacteriocins belong classes I and II, which are mainly heat-resistant peptides. No class III bigger heat-sensitive proteins, including phage tail-like from Unlike prophage lysins not regarded possibly because contribute autolysis, degrading host's own cell wall.Wild-type lactis strain LAC460, isolated spontaneously fermented idli batter, was examined for its activity. We sequenced genome, searched culture supernatant, created knock-out mutants find out source activity.The LAC460 shown kill other strains with protease- lytic Three were identified supernatant. The genes encoding three localized regions chromosome. By mutants, two lysins, namely LysL LysP, demonstrated be responsible resistant action consequence, could behave like targeting killing closely related bacteria. Hence, similar lysin-like novel type bacteriocins.

Language: Английский

Citations

8
Isolation and in vitro characterization of novel S. epidermidis phages for therapeutic applications DOI Creative Commons

Vida Štrancar,

Monika Marušić,

Jasmina Tušar

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: May 24, 2023

S. epidermidis is an important opportunistic pathogen causing chronic prosthetic joint infections associated with biofilm growth. Increased tolerance to antibiotic therapy often requires prolonged treatment or revision surgery. Phage currently used as compassionate use and continues be evaluated for its viability adjunctive alternative caused by prevent relapses. In the present study, we report isolation in vitro characterization of three novel lytic phages. Their genome content analysis indicated absence resistance genes virulence factors. Detailed investigation phage preparation any prophage-related contamination demonstrated importance selecting appropriate hosts development from outset. The isolated phages infect a high proportion clinically relevant strains several other coagulase-negative species growing both planktonic culture biofilm. Clinical differing their phenotype profile were selected further identify possible mechanisms behind increased

Language: Английский

Citations

7
The effect of phage-antibiotic combination strategy on multidrug-resistant Acinetobacter baumannii biofilms DOI
Hilal Başak Erol, Banu Kaşkatepe,

Sulhiye Yıldız

et al.

Journal of Microbiological Methods, Journal Year: 2023, Volume and Issue: 210, P. 106752 - 106752

Published: June 1, 2023

Language: Английский

Citations

7
Prevalence of virulence- and antibiotic resistance-associated genotypes and phenotypes in Staphylococcus aureus strains from the food sector compared to clinical and cow mastitis isolates DOI Creative Commons
Andrea Jurado, Lucía Fernández, Ana Rodrı́guez

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 29, 2024

Background Infections by the pathogen Staphylococcus aureus currently represent one of most serious threats to human health worldwide, especially due production enterotoxins and ability form biofilms. These structures acquisition antibiotic resistance limit action antibiotics disinfectants used combat this microorganism in industry clinic. Methods This work reports a comparative phenotypic genotypic study 18 S. strains from different origins: clinical samples, milk mastitic cows food surfaces, which were isolated Northern Spain. Results Genetically, very diverse but, cases, closer proximity was observed for those same source. Notably, average number virulence genes not significantly sector. Of strains, 10 coded at least enterotoxin, four them carried 6 or 7 enterotoxin genes. The latter all veterinary isolates. Most prophages, plasmids and/or pathogenicity islands. Regarding resistance, although phenotypically showed antibiotic, only identified 44.5% being mastitis isolates with lowest prevalence. Virulence-related properties such as haemolytic activity, staphyloxanthin production, biofilm-forming capacity spreading widely distributed amongst Conclusions Our results indicate that factors, biofilm formation can be found environments, including industry, some these traits are more prevalent infections humans. emphasizes on importance monitoring spread determinants samples environment, but also along chain, strategy falls under prism one-health approach.

Language: Английский

Citations

2
A mechanism-based pathway toward administering highly active N-phage cocktails DOI Creative Commons
Nicholas M. Smith, Thomas D. Nguyen, Wai Hoe Chin

et al.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 15, 2023

Bacteriophage (phage) therapy is being explored as a possible response to the antimicrobial resistance public health emergency. Administering mixture of different phage types cocktail one proposed strategy for therapeutic applications, but optimal method formulating cocktails remains major challenge. Each strain has complex pharmacokinetic/pharmacodynamic (PK/PD) properties which depend on nano-scale size, target-mediated, self-dosing nature each strain, and rapid selection resistant subpopulations. The objective this study was explore pharmacodynamics (PD) three unique clinically relevant anti- Pseudomonas phages after simulation dynamic dosing strategies. Hollow Fiber Infection Model (HFIM) an in vitro system that mimics vivo pharmacokinetics (PK) with high fidelity, providing opportunity quantify bacteria concentration profiles over clinical time scales rich sampling. Exogenous monotherapy-bolus (producing max concentrations C = 7 log 10 PFU/mL) regimens LUZ19, PYO2, E215 produced aeruginosa nadirs 0, 2.14, or 2.99 CFU/mL 6 h treatment, respectively. combination bolus (LUZ19 + PYO2 LUZ19 E215) resulted bacterial reduction <2 CFU/mL. In contrast, monotherapy continuous infusion steady-state ss,avg 2 less effective at reducing densities. Specifically, failed reduce density. Next, mechanism-based mathematical model developed describe pharmacodynamics, phage–phage competition, phage-dependent adaptive resistance. Monte Carlo simulations supported dose regimens, predicting lower counts compared prolonged infusions. Together, silico evaluation course will better guide patterns administration individual cocktail.

Language: Английский

Citations

6
Characterization and genomic analysis of novel bacteriophage NK20 to revert colistin resistance and combat pandrug-resistant Klebsiella pneumoniae in a rat respiratory infection model DOI
Lamiaa A. Al-Madboly, Ahmed Abdelaziz,

Amal M. Abo-Kamer

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 322, P. 121639 - 121639

Published: March 30, 2023

Language: Английский

Citations

5
Gut microbiome associated dysbiosis: Limited regimens and expanding horizons of phage therapy DOI Creative Commons
Biplab Singha, Bhupendra Singh Rawat,

Ramya Venkataraman

et al.

Aspects of Molecular Medicine, Journal Year: 2023, Volume and Issue: 2, P. 100029 - 100029

Published: Nov. 21, 2023

Human gut microbiota plays an important role in health, broadly influencing metabolism to the immune system and drug resistance pathogenic colonization. Since antibiotic is on rise, wide-spectrum antibiotics are known have deleterious effects microbial biodiversity targeted therapeutic interventions must be made. Bacteriophages viruses that commonly recognized a high level of specificity, targeting only intended bacterial species without disrupting overall community. Advancements genomics, bioinformatics, synthetic biology led us identification design phages, capable precisely specific pathogens. In this review article, we aim discuss both challenges opportunities integrating phage therapies into clinical practice, discussing limitations traditional therapy as it pertains manipulation microbiome.

Language: Английский

Citations

5
Using Genomic Tools to Predict Antimicrobial Resistance and Markers in Clinical Bacterial Samples DOI Open Access
Tony H. Chang, Julie D. Pourtois, Naomi L. Haddock

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 3, 2024

Abstract Antimicrobial resistance (AMR) poses a critical threat to hospital infections particularly in the context of hospital-acquired (HAIs). This study leverages genomic tools predict AMR and identify markers clinical bacterial samples associated with HAIs. Using comprehensive phenotypic analyses, we evaluated genetic profiles Pseudomonas aeruginosa Staphylococcus aureus uncover mechanisms. Our results demonstrate that tools, such as CARD-RGI Solu platform, can accurately genes phenotypes nosocomial pathogens. These findings underscore potential integrating approaches into practice enhance management resistant settings inform development novel antimicrobial strategies. Importance investigates impact prophages on antibiotic two clinically significant bacteria, aureus. Understanding how influence mechanisms these pathogens is crucial, known for its role chronic cystic fibrosis patients, while aureus, including MRSA strains, leading cause infections. By exploring relationship between prophage presence resistance, this research provides insights could more effective treatment strategies our ability combat antibiotic-resistant infections, ultimately improving patient outcomes public health.

Language: Английский

Citations

1