Completing the BASEL phage collection to unlock hidden diversity for systematic exploration of phage–host interactions DOI Creative Commons
Dorentina Humolli,

Damien Piel,

Enea Maffei

et al.

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(4), P. e3003063 - e3003063

Published: April 7, 2025

Research on bacteriophages, the viruses infecting bacteria, has fueled development of modern molecular biology and inspired their therapeutic application to combat bacterial multidrug resistance. However, most work so far focused a few model phages which impedes direct applications these findings in clinics suggests that vast potential powerful remained untapped. We have therefore recently composed BASEL collection Escherichia coli (BActeriophage SElection for your Laboratory), made relevant diversity E. K-12 laboratory strain accessible community. These are widely used, but assorted limited by host. now genetically overcome two major limitations K-12, its lack O-antigen glycans presence resident immunity. Restoring expression resulted isolation diverse additional viral groups like Kagunavirus , Nonanavirus Gordonclarkvirinae Gamaleyavirus while eliminating all known antiviral defenses additionally enabled us isolate Wifcevirus genus. Even though some appear be common nature, no from any them had previously been isolated using strains, they thus largely understudied. Overall, 37 new phage isolates added complete collection. were deeply characterized genomically phenotypically with regard host receptors, sensitivity defense systems, range. results highlighted dominant roles barrier recognition restriction-modification systems anticipate completed will propel research phage–host interactions mechanisms, deepening our understanding ecology fostering innovations biotechnology antimicrobial therapy.

Language: Английский

Prevention and Control of Human Salmonella enterica Infections: An Implication in Food Safety DOI Creative Commons
Mwanaisha Mkangara

International Journal of Food Science, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 26

Published: Sept. 11, 2023

Salmonella is a foodborne zoonotic pathogen causing diarrhoeal disease to humans after consuming contaminated water, animal, and plant products. The bacterium the third leading cause of human death among diseases worldwide. Therefore, salmonellosis public health concern demanding integrated interventions against causative agent, enterica. prevention in intricate due several factors, including an immune-stable individual infected with S. enterica continuing shed live bacteria without showing any clinical signs. Similarly, asymptomatic animals are source food Furthermore, products animal origin menace industries biofilms, which enhance colonization, persistence, survival on equipment. resulting from equipment offset economic competition partner institutions international business. most worldwide prevalent broad-range serovars affecting Typhimurium Enteritidis, poultry products, others, primary infection. broader range creates over multiple strategies for preventing controlling contamination foods safety humans. Among spread include biosecurity measures, isolation quarantine, epidemiological surveillance, farming systems, herbs spices, vaccination. Other measures application phages, probiotics, prebiotics, nanoparticles reduced capped antimicrobial agents. Salmonella-free such as beef, pork, meat, eggs, milk, foods, vegetables fruits, will prevent This review explains infection caused by quality

Language: Английский

Citations

60
CRISPR-Cas-Based Antimicrobials: Design, Challenges, and Bacterial Mechanisms of Resistance DOI Creative Commons
Arianna Mayorga-Ramos, Johana Zúñiga-Miranda, Saskya E. Carrera-Pacheco

et al.

ACS Infectious Diseases, Journal Year: 2023, Volume and Issue: 9(7), P. 1283 - 1302

Published: June 22, 2023

The emergence of antibiotic-resistant bacterial strains is a source public health concern across the globe. As discovery new conventional antibiotics has stalled significantly over past decade, there an urgency to develop novel approaches address drug resistance in infectious diseases. use CRISPR-Cas-based system for precise elimination targeted populations holds promise as innovative approach antimicrobial agent design. CRISPR-Cas targeting celebrated its high versatility and specificity, offering excellent opportunity fight antibiotic pathogens by selectively inactivating genes involved resistance, biofilm formation, pathogenicity, virulence, or viability. strategy can enact effects two approaches: inactivation chromosomal curing plasmids encoding resistance. In this Review, we provide overview main systems utilized creation these antimicrobials, well highlighting promising studies field. We also offer detailed discussion about most commonly used mechanisms delivery: bacteriophages, nanoparticles, conjugative plasmids. Lastly, possible interference that should be considered during intelligent design approaches.

Language: Английский

Citations

57
New Frontiers in CRISPR: Addressing Antimicrobial Resistance with Cas9, Cas12, Cas13, and Cas14 DOI Creative Commons
Ahmed S.A. Ali Agha, Ali Al‐Samydai, Talal Aburjaı

et al.

Heliyon, Journal Year: 2025, Volume and Issue: 11(2), P. e42013 - e42013

Published: Jan. 1, 2025

The issue of antimicrobial resistance (AMR) poses a major challenge to global health, evidenced by alarming mortality predictions and the diminishing efficiency conventional drugs. CRISPR-Cas system has proven be powerful tool in addressing this challenge. It originated from bacterial adaptive immune mechanisms gained significant recognition scientific community. This review aims explore applications technologies combating AMR, evaluating their effectiveness, challenges, potential for integration into current strategies. We conducted comprehensive recent literature databases such as PubMed Web Science, focusing on studies that employ against AMR. offer transformative approach combat with extend beyond traditional Integrating these existing methods could significantly enhance our ability manage potentially reverse growing problem resistance. Future research should address technical ethical barriers facilitate safe effective clinical environmental applications. underscores necessity interdisciplinary collaboration international cooperation harness full fight superbugs.

Language: Английский

Citations

2
Enhancing bacteriophage therapeutics through in situ production and release of heterologous antimicrobial effectors DOI Creative Commons
Jiemin Du, Susanne Meile,

Jasmin Baggenstos

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 20, 2023

Bacteriophages operate via pathogen-specific mechanisms of action distinct from conventional, broad-spectrum antibiotics and are emerging as promising alternative antimicrobials. However, phage-mediated killing is often limited by bacterial resistance development. Here, we engineer phages for target-specific effector gene delivery host-dependent production colicin-like bacteriocins cell wall hydrolases. Using urinary tract infection (UTI) a model, show how heterologous phage therapeutics (HEPTs) suppress improve uropathogen dual phage- effector-mediated targeting. Moreover, designed HEPTs to control polymicrobial communities through effectors with cross-genus activity. phage-based companion diagnostics, identified potential HEPT responder patients treated their urine ex vivo. Compared wildtype phage, colicin E7-producing demonstrated superior patient E. coli bacteriuria. Arming paves the way successful UTI treatment represents versatile tool enhance adapt precision

Language: Английский

Citations

41
Synthetic biology-inspired cell engineering in diagnosis, treatment, and drug development DOI Creative Commons

Ninglin Zhao,

Yingjie Song,

Xiangqian Xie

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 11, 2023

Abstract The fast-developing synthetic biology (SB) has provided many genetic tools to reprogram and engineer cells for improved performance, novel functions, diverse applications. Such cell engineering resources can play a critical role in the research development of therapeutics. However, there are certain limitations challenges applying genetically engineered clinical practice. This literature review updates recent advances biomedical applications, including diagnosis, treatment, drug development, SB-inspired engineering. It describes technologies relevant examples experimental setup that may significantly impact biomedicine field. At last, this concludes results with future directions optimize performances gene circuits regulate therapeutic activities cell-based specific diseases.

Language: Английский

Citations

40
Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine DOI Creative Commons
Susanne Meile, Jiemin Du, Samuel Staubli

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 20, 2023

Abstract The rapid detection and species-level differentiation of bacterial pathogens facilitates antibiotic stewardship improves disease management. Here, we develop a bacteriophage-based diagnostic assay to detect the most prevalent causing urinary tract infections: Escherichia coli, Enterococcus spp., Klebsiella spp. For each uropathogen, two virulent phages were genetically engineered express nanoluciferase reporter gene upon host infection. Using 206 patient urine samples, phage-induced bioluminescence was quantified identify bacteriuria benchmarked against conventional urinalysis. Overall, E. coli , detected with high sensitivity (68%, 78%, 87%), specificity (99%, 99%, 99%), accuracy (90%, 94%, 98%) at resolution ≥10 3 CFU/ml within 5 h. We further demonstrate how in can be used predict phage antibacterial activity, demonstrating future potential as companion diagnostics that guide patient-phage matching prior therapeutic application.

Language: Английский

Citations

38
L-form conversion in Gram-positive bacteria enables escape from phage infection DOI Creative Commons
Jan C. Wohlfarth,

Miki Feldmüller,

Alissa Schneller

et al.

Nature Microbiology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 30, 2023

Abstract At the end of a lytic bacteriophage replication cycle in Gram-positive bacteria, peptidoglycan-degrading endolysins that cause explosive cell lysis host can also attack non-infected bystander cells. Here we show osmotically stabilized environments, Listeria monocytogenes evade phage predation by transient conversion to wall-deficient L-form state. This escape is triggered disintegrating wall from without, leading turgor-driven extrusion wall-deficient, yet viable Remarkably, absence predation, L-forms quickly revert walled These findings suggest represents population-level persistence mechanism complete eradication attack. Importantly, demonstrate phage-mediated switching urinary tract pathogen Enterococcus faecalis human urine, which underscores this route may be widespread and has important implications for phage- endolysin-based therapeutic interventions.

Language: Английский

Citations

30
The Biotechnological Application of Bacteriophages: What to Do and Where to Go in the Middle of the Post-Antibiotic Era DOI Creative Commons
Su Jin Jo, Jun Kwon, Sang Guen Kim

et al.

Microorganisms, Journal Year: 2023, Volume and Issue: 11(9), P. 2311 - 2311

Published: Sept. 13, 2023

Amid the escalating challenges of antibiotic resistance, bacterial infections have emerged as a global threat. Bacteriophages (phages), viral entities capable selectively infecting bacteria, are gaining momentum promising alternatives to traditional antibiotics. Their distinctive attributes, including host specificity, inherent self-amplification, and potential synergy with antibiotics, render them compelling candidates. Phage engineering, burgeoning discipline, involves strategic modification bacteriophages enhance their therapeutic broaden applications. The integration CRISPR-Cas systems facilitates precise genetic modifications, enabling phages serve carriers functional genes/proteins, thereby enhancing diagnostics, drug delivery, therapy. engineering holds promise in transforming precision medicine, addressing advancing diverse Emphasizing profound phages, this review underscores pivotal role combatting diseases highlights significance post-antibiotic era.

Language: Английский

Citations

25
Bacteriophages as nanocarriers for targeted drug delivery and enhanced therapeutic effects DOI Creative Commons
Stephen Chijioke Emencheta, Adaeze Linda Onugwu, Chisom F. Kalu

et al.

Materials Advances, Journal Year: 2024, Volume and Issue: 5(3), P. 986 - 1016

Published: Jan. 1, 2024

The bioengineering of phages to display ligands leads specific targeting, reduced toxicity, enhanced cellular uptake an incorporated drug/gene and, ultimately, increased therapeutic efficacy.

Language: Английский

Citations

12
Engineering bacteriophages for targeted superbug eradication DOI
Ghazal Ghaznavi,

Parisa Vosough,

Abdolmajid Ghasemian

et al.

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: Feb. 11, 2025

Language: Английский

Citations

1