«The LAMP-CRISPR-Cas13a technique for detecting CBASS-mechanism of phage resistance in bacteria» DOI Creative Commons
Concha Ortiz-Cartagena,

Patricia Fernández-Grela,

Lucía Armán

et al.

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

Published: Dec. 20, 2024

ABSTRACT Antimicrobial resistance (AMR) is an important threat to public health that has led the development of innovative alternative treatments for bacterial infections, such as phage therapy. However, one greatest disadvantages therapy generation phage-resistant mutants via defence mechanisms, which are mainly contained in genomic islands (GIs) and controlled by quorum sensing (QS) network. In this study, 309 pathogenic (PAIs) harbouring a total 22.1 % proteins related anti-phage (APD) were detected genome 48 K. pneumoniae strains. Several type I II CBASS systems also strains, but only 2 located PAIs. We constructed knockout strain, not expressing cyclase gene from system present PAIs, study regulatory role QS gene. As abortive infection (Abi) system, regulating cell viability was assessed. The strain confirmed targeting LAMP-CRISPR-Cas13a technique specifically gene, same protocol used detect main these systems, i.e. APECO1. findings demonstrate network systems. Finally, first work biotechnological application rapid-technique (<2 hours) optimizing detecting predicting potential inefficacy therapeutic thus improving patient prognosis.

Language: Английский

Oral bacteriophages and their potential as adjunctive treatments for periodontitis: a narrative review DOI Creative Commons
Mwila Kabwe, Joseph Tucci, Ivan Darby

et al.

Journal of Oral Microbiology, Journal Year: 2025, Volume and Issue: 17(1)

Published: Feb. 25, 2025

Background There is no specific cure for periodontitis and treatment symptomatic, primarily by physical removal of the subgingival plaque biofilm. Current non-surgical periodontal therapy becomes less effective as pocket depth increases such new adjunctive treatments are required. The development antibiotic resistance has driven a recent resurgence interest in bacteriophage therapy.

Language: Английский

Citations

1

Going viral: The role of mobile genetic elements in bacterial immunity DOI
Beatriz Beamud, Fabienne Benz,

David Bikard

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(6), P. 804 - 819

Published: June 1, 2024

Language: Английский

Citations

8

A Klebsiella-phage cocktail to broaden the host range and delay bacteriophage resistance both in vitro and in vivo DOI Creative Commons

Huanchang Chen,

Haifeng Liu, Yanchun Gong

et al.

npj Biofilms and Microbiomes, Journal Year: 2024, Volume and Issue: 10(1)

Published: Nov. 14, 2024

Bacteriophages (phages), viruses capable of infecting and lysing bacteria, are a promising alternative for treating infections from hypervirulent, antibiotic-resistant pathogens like Klebsiella pneumoniae, though narrow host range phage resistance remain challenges. In this study, the hypervirulent K. pneumoniae NTUH-K2044 was used to purify ΦK2044, while two ΦK2044-resistant strains were further phages: ΦKR1, ΦKR8 hospital sewage. A detailed characterization showed that ΦK2044 specifically killed KL1 capsule-type ΦKR1 targeted 13 different capsular serotypes. The cocktail (ΦK2044 + ΦKR8) effectively in biofilms, pre-treatment biofilm formation, delayed phage-resistance. improved 7-day survival Galleria mellonella mouse models therapeutic potential catheter model. summary, proof-of-principle has broad range, including highly drug-resistant serves as starting point optimizing therapy.

Language: Английский

Citations

7

Regulation of anti-phage defense mechanisms by using cinnamaldehyde as a quorum sensing inhibitor DOI Creative Commons
Antonio Barrio-Pujante, Inés Bleriot, Lucía Blasco

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: June 26, 2024

Multidrug-resistant bacteria and the shortage of new antibiotics constitute a serious health problem. This problem has led to increased interest in use bacteriophages, which have great potential as antimicrobial agents but also carry risk inducing resistance. The objective present study was minimize development phage resistance Klebsiella pneumoniae strains by inhibiting quorum sensing (QS) thus demonstrate role QS regulating defense mechanisms. Cinnamaldehyde (CAD) added K. cultures inhibit signaling system anti-phage mechanism. inhibitory activity CAD confirmed reduction quantitative expression lsrB gene (AI-2 pathway) proteomic analysis. infection assays showed that able infect previously resistant strain added. results were using Thus, defense-related proteins from different systems, such cyclic oligonucleotide-based bacterial systems (CBASS), restriction-modification (R-M) clustered regularly interspaced short palindromic repeat-Cas (CRISPR-Cas) system, bacteriophage control (BCI), with not CAD. When inhibited combined treatment, related proliferation, tail fiber protein, cell division protein DamX, outer membrane channel TolC, detected. Inhibition reduces pneumoniae, resulting phage, significant increase proliferation growth. inhibitors could be considered for therapeutic application including them cocktails or phage-antibiotic combinations enhance synergistic effects reduce emergence

Language: Английский

Citations

4

Phage-encoded depolymerases as a strategy for combating multidrug-resistant Acinetobacter baumannii DOI Creative Commons
Md Minarul Islam,

Nasir Uddin Mahbub,

Woo Shik Shin

et al.

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

Published: Oct. 24, 2024

, a predominant nosocomial pathogen, represents grave threat to public health due its multiple antimicrobial resistance. Managing patients afflicted with severe infections caused by drug-resistant

Language: Английский

Citations

4

Study of the probability of resistance to phage infection in a collection of clinical isolates of P s eudomonas aeruginosa in relation to the presence of Pf phages DOI Creative Commons
Lucía Blasco, Clara Ibarguren-Quiles, Carla López-Causapé

et al.

Microbiology Spectrum, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

ABSTRACT Pseudomonas aeruginosa is a bacterial pathogen that major cause of lung infections in cystic fibrosis (CF) and other patients. Isolates P. from CF patients commonly carry filamentous phages (Pf phages), which constitute family temperate known to be related biofilm production antibiotic sequestration. In this study, we identified 12 new Pf phage genomes collection clinical isolates Study the anti-phage defense systems revealed presence 89 such systems, eight were encoded genomes. Finally, although weak relation between resistance infection number was detected, it observed these phages. IMPORTANCE Bacteria harbor wide range mechanisms avoid hamper application therapy because they can lead rapid acquisition resistance. found genome presents 56% . The high prevalence underlines importance our findings about newly discovered role infections. Thus, knowledge anti-defense system could useful assessing possible treat an infectious disease.

Language: Английский

Citations

0

Phage treatment of multidrug-resistant bacterial infections in humans, animals, and plants: The current status and future prospects DOI Creative Commons

Omor Faruk,

Zilhas Ahmed Jewel,

Sanjoy Bairagi

et al.

Infectious Medicine, Journal Year: 2025, Volume and Issue: 4(1), P. 100168 - 100168

Published: Feb. 6, 2025

Phages, including the viruses that lyse bacterial pathogens, offer unique therapeutic advantages, their capacity to antibiotic-resistant bacteria and disrupt biofilms without harming host microbiota. The lack of new effective antibiotics growing limitations existing have refocused attention on phage therapy as an option in complex clinical cases such burn wounds, cystic fibrosis, pneumonia. This review describes preclinical studies which has been both human veterinary medicine, agricultural context. In addition, critical challenges, narrow range bacteriophages, possibility resistance, regulatory constraints widespread use therapy, are addressed. Future directions include optimizing through strategies ranging from cocktails broadening genetic modification, using phages vaccines or biocontrol agents. future, if can be efficiently delivered, maintained a stable state, phage-antibiotic synergy achieved, will much needed treatment options. However, successful implementation within current standards practice also require considerable development infrastructure greater public acceptance. closing, this highlights promise backup substitute for antibiotics. It proposes role significant adjunct to, even replacement for, treating multidrug-resistant infections.

Language: Английский

Citations

0

Chemical inhibition of a bacterial immune system DOI Creative Commons
Zhiyu Zang,

Olivia K. Duncan,

Dziugas Sabonis

et al.

Published: Feb. 21, 2025

Abstract The rise of antibiotic resistance motivates a revived interest in phage therapy. However, bacteria possess dozens anti-bacteriophage immune systems that confer to therapeutic phages. Chemical inhibitors these anti-phage could be employed as adjuvants overcome phage-based therapies. Here, we report can selectively inhibited by small molecules, thereby sensitizing phage-resistant We discovered class chemical inhibit the type II Thoeris system. These block biosynthesis histidine-ADPR intracellular ‘alarm’ signal ThsB and prevent ThsA from arresting replication. promiscuously diverse bacteria—including antibiotic-resistant pathogens. inhibition defense improved efficacy model therapy against strain P. aeruginosa mouse infection, suggesting potential. Furthermore, may tools dissect importance system for natural microbial communities.

Language: Английский

Citations

0

Reviving the past for a healthier future: ancient molecules and remedies as a solution to the antibiotic crisis DOI Creative Commons
Miguel Díaz‐Guerrero, Israel Castillo‐Juárez, Rimma Zurabián

et al.

Future Microbiology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13

Published: March 18, 2025

Options to combat bacterial infections are becoming scarce. We require innovative approaches enhance the discovery of effective antimicrobials capable combating bacteria resistant multiple or all antibiotics. These methods should either directly eliminate indirectly influence their viability by inhibiting virulence reducing resistance One interesting approach is analyze ancient remedies used treat infections, formulate them, and test them against modern microbes. This field has recently been named "ancientbiotics." allows us leverage centuries empirical knowledge accumulated, from traditional medicines across various cultures worldwide. The strategy already yielded promising formulations ESKAPE group nosocomial pathogens. Additionally, molecular de-extinction, which involves genome analysis extinct species search for useful antimicrobials, such as peptides, offers another avenue. In this review, we compile antimicrobial effects de-extinct molecules known science discuss possible new strategies further harness potential past fight rise superbugs.

Language: Английский

Citations

0

The LAMP-CRISPR-Cas13a technique for detecting the CBASS mechanism of phage resistance in bacteria DOI Creative Commons
Concha Ortiz-Cartagena,

Patricia Fernández-Grela,

Lucía Armán

et al.

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: March 24, 2025

Introduction Antimicrobial resistance (AMR) is a major public health threat, driving the need for alternative treatments such as phage therapy. However, bacterial defense mechanisms, often regulated by quorum sensing (QS) network and encoded in genomic islands (GIs), can generate phage-resistant mutants. Understanding these mechanisms essential optimizing Methods This study analyzed 48 Klebsiella pneumoniae strains to identify pathogenicity (PAIs) containing anti-phage (APD) proteins. We constructed knockout strain lacking cyclase gene from type II CBASS systems present PAIs investigate QS regulation its role cell viability. The LAMP-CRISPR-Cas13a technique was used confirm detect main I systems, i.e., APECO1. Results A total of 309 (PAIs), 22.1% proteins, were identified. Type APD also detected genome 48, K. strains, only two located PAIs. Alluding revealed be involved contained Finally, technology successfully cyclases habored respectively. Discussion findings highlight regulatory systems. Notably, this first develop an innovative biotechnological application rapid-technique (&lt;2 h), thereby helping optimize therapy detecting predicting potential inefficacy therapeutic phages thus improving patient prognosis.

Language: Английский

Citations

0