Unlocking data in Klebsiella lysogens to predict capsular type-specificity of phage depolymerases DOI Creative Commons
Robby Concha-Eloko, Rafael Sanjuán, Beatriz Beamud

et al.

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

Published: July 25, 2024

Viral entry is a critical step in the infection process. Klebsiella spp. and other clinically relevant bacteria often express complex polysaccharide capsule that acts as barrier to phage entry. In turn, most phages encode depolymerases for removal. This virus-host arms race has led extensive genetic diversity both capsules depolymerases, complicating our ability understand their interaction. study exploits information encoded prophages model interplay between bacteria, prophages, using graph neural network sequence clustering-based method. Both approaches showed significant predictive capsular tropism and, importantly, were transferrable lytic phages. addition creating comprehensive database linking depolymerase sequences specific targets, this demonstrates predictability of phage-host interactions at subspecies level, providing new insights improving therapeutic industrial applicability

Language: Английский

Factors mediating Acinetobacter baumannii biofilm formation: Opportunities for developing therapeutics DOI Creative Commons
Kirti Upmanyu, Qazi Mohd. Rizwanul Haq, Ruchi Singh

et al.

Current Research in Microbial Sciences, Journal Year: 2022, Volume and Issue: 3, P. 100131 - 100131

Published: Jan. 1, 2022

has notably become a superbug due to its mounting risk of infection and escalating rates antimicrobial resistance, including colistin, the last-resort antibiotic. Its propensity form biofilm on biotic abiotic surfaces contributed majority nosocomial infections. Bacterial cells in biofilms are resistant antibiotics host immune response, pose challenges treatment. Therefore current scenario urgently requires development novel therapeutic strategies for successful treatment outcomes. This article provides holistic understanding sequential events regulatory mechanisms directing

Language: Английский

Citations

51

Combination of genetically diverse Pseudomonas phages enhances the cocktail efficiency against bacteria DOI Creative Commons
Ampapan Naknaen,

Thanadon Samernate,

Wichanan Wannasrichan

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: June 1, 2023

Phage treatment has been used as an alternative to antibiotics since the early 1900s. However, bacteria may acquire phage resistance quickly, limiting use of treatment. The combination genetically diverse phages displaying distinct replication machinery in cocktails therefore become a novel strategy improve therapeutic outcomes. Here, we isolated and studied lytic (SPA01 SPA05) that infect wide range clinical Pseudomonas aeruginosa isolates. These relatively small myophages have around 93 kbp genomes with no undesirable genes, 30-min latent period, reproduce high number progenies, ranging from 218 240 PFU per infected cell. Even though both lyse their hosts within 4 h, phage-resistant emerge during Considering SPA01-resistant cross-resist SPA05 vice versa, combining SPA01 for cocktail would be ineffective. According decreased adsorption rate resistant isolates, one anti-phage mechanisms occur through modification receptors on target cells. All however, are susceptible nucleus-forming jumbophages (PhiKZ PhiPA3), which SPA05, suggesting recognize different receptor entry. these jumbophage PhiKZ outperforms other tested combinations terms bactericidal activity effectively suppresses emergence resistance. This finding reveals effectiveness phage-composed reducing bacterial growth prolonging evolution

Language: Английский

Citations

30

Acinetobacter Baumannii Phages: Past, Present and Future DOI Creative Commons

Qihang Tu,

Mingfang Pu,

Yahao Li

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(3), P. 673 - 673

Published: March 3, 2023

Acinetobacter baumannii (A. baumannii) is one of the most common clinical pathogens and a typical multi-drug resistant (MDR) bacterium. With increase drug-resistant A. infections, it urgent to find some new treatment strategies, such as phage therapy. In this paper, we described different drug resistances basic properties phages, analyzed interaction between phages their hosts, focused on therapies. Finally, discussed chance challenge This paper aims provide more comprehensive understanding theoretical support for application phages.

Language: Английский

Citations

26

Alginate microbeads and hydrogels delivering meropenem and bacteriophages to treat Pseudomonas aeruginosa fracture-related infections DOI
Baixing Chen,

Luis Ponce Benavente,

Marco Chittò

et al.

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 364, P. 159 - 173

Published: Oct. 31, 2023

Language: Английский

Citations

21

Improving phage therapy by evasion of phage resistance mechanisms DOI Creative Commons
Inés Bleriot, Olga Pacios, Lucía Blasco

et al.

JAC-Antimicrobial Resistance, Journal Year: 2023, Volume and Issue: 6(1)

Published: Dec. 28, 2023

Abstract Antibiotic failure is one of the most worrisome threats to global health. Among new therapeutic efforts that are being explored, use bacteriophages (viruses kill bacteria), also known as ‘phages’, extensively studied a strategy target bacterial pathogens. However, main drawbacks phage therapy plethora defence mechanisms bacteria defend themselves against phages. This review aims summarize approaches evaluated overcome systems, including innovative applied: circumvention receptor mutations; modification prophages; targeting CRISPR-Cas systems and biofilm matrix; engineering safer more efficacious phages; inhibition anti-persister strategies used by bacteria.

Language: Английский

Citations

19

Synergistic Antimicrobial Effects of Phage vB_AbaSi_W9 and Antibiotics against Acinetobacter baumannii Infection DOI Creative Commons
Yoon-Jung Choi, Shukho Kim, Minsang Shin

et al.

Antibiotics, Journal Year: 2024, Volume and Issue: 13(7), P. 680 - 680

Published: July 22, 2024

Acinetobacter baumannii is a challenging multidrug-resistant pathogen in healthcare. Phage vB_AbaSi_W9 (GenBank: PP146379.1), identified our previous study, shows lytic activity against 26 (89.66%) of 29 carbapenem-resistant (CRAB) strains with various sequence types (STs). It promising candidate for CRAB treatment; however, its efficiency insufficient complete bacterial lysis. Therefore, this study aimed to investigate the clinical utility phage by identifying antimicrobial agents that show synergistic effects when combined it. The A. ATCC17978 strain was used as host vB_AbaSi_W9. Adsorption and one-step growth assays were performed at MOIs 0.001 0.01, respectively. Four belonging different types, KBN10P04948 (ST191), LIS2013230 (ST208), KBN10P05982 (ST369), KBN10P05231 (ST451), phage-antibiotic synergy. Five antibiotics tested following concentration: meropenem (0.25-512 µg/mL); colistin, tigecycline, rifampicin (0.25-256 ampicillin/sulbactam (0.25/0.125-512/256 µg/mL). vitro effect verified through an vivo mouse infection model. demonstrated 90% adsorption cells 1 min, 20 min latent period, burst size 114 PFU/cell. Experiments combining pronounced tigecycline rifampicin. In model infected group treated (100 μg/mL) (MOI 1) achieved 100% survival rate-a significant improvement over phage-only treatment (8.3% rate) or antibiotic-only (25% groups. bacteriophage excellent synergy rifampicin, suggesting potential candidates combination therapy treating infections.

Language: Английский

Citations

7

Biological Properties of 12 Newly Isolated Acinetobacter baumannii-Specific Bacteriophages DOI Creative Commons
Natalia Bagińska, Marek Harhala, Martyna Cieślik

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(1), P. 231 - 231

Published: Jan. 13, 2023

Infections with the opportunistic Gram-negative bacterium Acinetobacter baumannii pose a serious threat today, which is aggravated by growing problem of multi-drug resistance among bacteria, caused overuse antibiotics. Treatment infections antibiotic-resistant A. strains use phage therapy not only promising alternative, but sometimes option. Therefore, phages specific for clinical resistant were searched in environmental, municipal, and hospital wastewater samples collected from different locations Poland. The conducted research allowed us to determine biological properties morphology tested phages. As result our research, 12 baumannii, 11 turned out be temperate one lytic, isolated. Their lytic spectra ranged 75%. plaques formed most small transparent, while them relatively large clearly marked ‘halo’ effect. Based on Transmission Electron Microscopy (TEM), have been classified as siphoviruses (only was podovirus). All icosahedral capsid symmetry, long tail. Optimal multiplicity (MOIs) adsorption rate also determined. MOI values varied depending phage—from 0.001 10. similarities known bacteriophages, baumannii-specific proposed belong Beijerinckvirinae Junivirinae subfamilies. This study provides an additional tool fight against this important pathogen may boost interest alternative supplement current

Language: Английский

Citations

14

Loss of a Branch Sugar in the Acinetobacter baumannii K3-Type Capsular Polysaccharide Due To Frameshifts in the gtr6 Glycosyltransferase Gene Leads To Susceptibility To Phage APK37.1 DOI Creative Commons
Olga Y. Timoshina, Anastasiya A. Kasimova, Mikhail M. Shneider

et al.

Microbiology Spectrum, Journal Year: 2023, Volume and Issue: 11(1)

Published: Jan. 18, 2023

The type of capsular polysaccharide (CPS) on the cell surface Acinetobacter baumannii can determine specificity lytic bacteriophage under consideration for therapeutic use. Here, we report isolation a phage an extensively antibiotic resistant ST2 A. isolate AB5001 that carries KL3 CPS biosynthesis gene cluster predicting K3-type CPS. As did not infect isolates carrying or KL22 and known to produce K3 CPS, structure isolated from was determined. produced variant form, K3-v1, lacks β-d-GlсpNAc side chain attached d-Galp residue in structure. Inspection sequence genomes other phage-susceptible with locus revealed single-base deletions gtr6, causing loss Gtr6 glycosyltransferase adds missing d-GlсpNAc Hence, presence this sugar profoundly restricts ability digest 41-kb linear double-stranded DNA (dsDNA) genome identical K37-producing thus named APK37.1. APK37.1 also infected KL116. Consistent this, K3-v1 resembles K37 K116 structures. is Friunavirus belonging Autographiviridae family. phage-encoded tail spike depolymerase DpoAPK37.1 closely related Dpo encoded by sequenced Friunaviruses, including APK37 APK116. IMPORTANCE Lytic have potential treatment otherwise untreatable antibiotic-resistant bacteria. For baumannii, most exhibit surface. However, resistance arise via mutations genes abolish receptor. show result alteration final rather than deletion capsule layer hence affect newly reported podophage strains producing

Language: Английский

Citations

14

Understanding the biofilm development of Acinetobacter baumannii and novel strategies to combat infection DOI
Naji Naseef Pathoor,

Akshaya Viswanathan,

Gulshan Wadhwa

et al.

Apmis, Journal Year: 2024, Volume and Issue: 132(5), P. 317 - 335

Published: March 5, 2024

Acinetobacter baumannii ( A. ) is a Gram‐negative, nonmotile, and aerobic bacillus emerged as superbug, due to increasing the possibility of infection accelerating rates antimicrobial agents. It recognized nosocomial pathogen its ability form biofilms. These biofilms serve defensive barrier, increase antibiotic resistance, make treatment more difficult. As result, current situation necessitates rapid emergence novel therapeutic approaches ensure successful outcomes. This review explores intricate relationship between biofilm formation resistance in , emphasizing role key virulence factors quorum sensing (QS) mechanisms that will lead infections facilitate insight into developing innovative method control infections. Furthermore, article looks promising for preventing on medically important surfaces potential methods eliminating preformed biofilms, which can address biofilm‐associated Modern advances emerging options such peptide (AMPs), nanoparticles (NPs), bacteriophage therapy, photodynamic therapy (PDT), other inhibitors assist readers understand landscape future prospects effectively treating

Language: Английский

Citations

5

Synergistic effects of bacteriophage cocktail and antibiotics combinations against extensively drug-resistant Acinetobacter baumannii DOI Creative Commons
Sanaz Rastegar, Mikael Skurnik, Omid Tadjrobehkar

et al.

BMC Infectious Diseases, Journal Year: 2024, Volume and Issue: 24(1)

Published: Oct. 26, 2024

The extensively drug-resistant (XDR) strains of Acinetobacter baumannii have become a major cause nosocomial infections, increasing morbidity and mortality worldwide. Many different treatments, including phage therapy, are attractive ways to overcome the challenges antibiotic resistance. This study investigates biofilm formation ability 30 XDR A. isolates efficacy cocktail four tempetate bacteriophages (SA1, Eve, Ftm, Gln) antibiotics (ampicillin/sulbactam, meropenem, colistin) in inhibiting degrading biofilms these strains. majority (83.3%) exhibited strong formation. bacteriophage showed varying degrees effectiveness against biofilms, with higher concentrations generally leading more significant inhibition degradation rates. antibiotics-bacteriophage combinations also enhanced biofilms. findings suggested that is an effective tool combating its depending on concentration. Combining improved removal indicating promising strategy for managing infections. These results contribute our understanding dynamics potential cocktails as novel therapeutic approach combat antibiotic-resistant bacteria.

Language: Английский

Citations

5