Phage Resistance Evolution Induces the Sensitivity of Specific Antibiotics in Pseudomonas aeruginosa PAO1

Xuan, Guanhua; Lin, Hong; Kong, Jiuna; Wang, Jingxue

doi:10.1128/spectrum.01356-22

Cited by 11 publications

(6 citation statements)

References 46 publications

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“…Cai et al revealed that ompC of Klebsiella pneumoniae was an independent receptor for the phage GH-K3 ( 45 ). Some outer membrane proteins of phage receptors had specific functions, such as antibiotic efflux pumps, etc ( 46 ). Burmeister et al reported that phage resistance in E. coli via tolC mutations, leading to a reduction in tetracycline and colistin resistance, revealing the trade-off between efflux pumps and phage resistance ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Design combinations of evolved phage and antibiotic for antibacterial guided by analyzing the phage resistance of poorly antimicrobial phage

Xu,

Ding,

Shi

et al. 2023

Microbiol Spectr

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Although antibiotics are the primary method against bacterial infections, the rapid emergence of antibiotic resistance has forced interest in alternative antimicrobial strategies. Phage has been considered a new biological antimicrobial agent due to its high effectiveness in treating bacterial infections. However, the applications of phage therapy have been limited by the quick development of phage-resistant bacteria. Therefore, more effective phage treatment strategies need to be explored guided by characterizing phage-resistant mutants. In this study, Pseudomonas plecoglossicida phage vB_PpS_SYP was isolated from the sewage but exhibited weak antibacterial activity caused by phage-resistant bacteria. Phage-resistant mutants were isolated and their whole genomes were analyzed for differences. The results showed that mutations in glycosyltransferase family 1 ( GT-1 ) and hypothetical outer membrane protein ( homP ) led to bacterial phage resistance. The GT-1 mutants had lower biofilm biomass and higher antibiotic sensitivity than wild-type strain. Phage SYP evolved a broader host range and improved antimicrobial efficacy to infect homP mutants. Therefore, we designed a strategy for combined antibiotic and evolved phage inhibition driven by the two phage-resistant mutants. The results showed that the combination was more effective against bacteria than either antibiotics or phage alone. Our findings presented a novel approach to utilizing poorly antimicrobial phages by characterizing their phage-resistant mutants, with the potential to be expanded to include phage therapy for a variety of pathogens. IMPORTANCE The rapid emergence of antibiotic resistance renews interest in phage therapy. However, the lack of efficient phages against bacteria and the emergence of phage resistance impaired the efficiency of phage therapy. In this study, the isolated Pseudomonas plecoglossicida phage exhibited poor antibacterial capacity and was not available for phage therapy. Analysis of phage-resistant mutants guided the design of antibacterial strategies for the combination of antibiotics with evolved phages. The combination has a good antibacterial effect compared to the original phage. Our findings facilitate ideas for the development of antimicrobial-incapable phage, which have the potential to be applied to the phage treatment of other pathogens.

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Section: Discussionmentioning

confidence: 99%

Design combinations of evolved phage and antibiotic for antibacterial guided by analyzing the phage resistance of poorly antimicrobial phage

Xu,

Ding,

Shi

et al. 2023

Microbiol Spectr

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“…In vitro treatment with bacteriophages and antibiotics has been able to significantly increase susceptibility and re-sensitization of MDR P. aeruginosa strains to antibiotics [20][21][22][23][24][25][26][27][28][29][30][31]. All these studies were performed by conducting assays to determine the minimum inhibitory concentration (MIC) for antibiotics and bacteriophages according to the Clinical and Laboratory Standards Institute (CLSI) broth microdilution protocol and the fractional inhibitory concentrations (FIC) of antibiotics in the presence of phages using the checkerboard method [32].…”

Section: In Vitro Modelsmentioning

confidence: 99%

Bacteriophage–Antibiotic Combination Therapy against Pseudomonas aeruginosa

et al. 2023

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Phage therapy is an alternative therapy that is being used as the last resource against infections caused by multidrug-resistant bacteria after the failure of standard treatments. Pseudomonas aeruginosa can cause pneumonia, septicemia, urinary tract, and surgery site infections mainly in immunocompromised people, although it can cause infections in many different patient profiles. Cystic fibrosis patients are particularly vulnerable. In vitro and in vivo studies of phage therapy against P. aeruginosa include both bacteriophages alone and combined with antibiotics. However, the former is the most promising strategy utilized in clinical infections. This review summarizes the recent studies of phage-antibiotic combinations, highlighting the synergistic effects of in vitro and in vivo experiments and successful treatments in patients.

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“…This adsorption inhibition via spontaneous mutations in genes involved with the status of the cell surface has been best characterized at the genomic level in the model phage-host system of Escherichia coli and its phage T4 12 , 13 . Several other studies have addressed this process in Gram-negative bacteria and their associated viruses 14 , 15 . Still, the knowledge about the relationship between the ecological costs of accumulating random mutations in the host genomes to achieve phage resistance, such as survival in adverse conditions, and/or the ability to remain virulent, is limited.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous mutations in hlyD and tuf genes result in resistance of Dickeya solani IPO 2222 to phage ϕD5 but cause decreased bacterial fitness and virulence in planta

Sokolova

Smolarska

Bartnik

et al. 2023

Sci Rep

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Lytic bacteriophages able to infect and kill Dickeya spp. can be readily isolated from virtually all Dickeya spp. containing environments, yet little is known about the selective pressure those viruses exert on their hosts. Two spontaneous D. solani IPO 2222 mutants (0.8% of all obtained mutants), DsR34 and DsR207, resistant to infection caused by lytic phage vB_Dsol_D5 (ΦD5) were identified in this study that expressed a reduced ability to macerate potato tuber tissues compared to the wild-type, phage-susceptible D. solani IPO 2222 strain. Genome sequencing revealed that genes encoding: secretion protein HlyD (in mutant DsR34) and elongation factor Tu (EF-Tu) (in mutant DsR207) were altered in these strains. These mutations impacted the DsR34 and DsR207 proteomes. Features essential for the ecological success of these mutants in a plant environment, including their ability to use various carbon and nitrogen sources, production of plant cell wall degrading enzymes, ability to form biofilms, siderophore production, swimming and swarming motility and virulence in planta were assessed. Compared to the wild-type strain, D. solani IPO 2222, mutants DsR34 and DsR207 had a reduced ability to macerate chicory leaves and to colonize and cause symptoms in growing potato plants.

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Phage Resistance Evolution Induces the Sensitivity of Specific Antibiotics in Pseudomonas aeruginosa PAO1

Abstract: Bacteria frequently encounter the selection pressure from both antibiotics and lytic phages. Little is known about the evolutionary interactions between antibiotics and phages.

Cited by 11 publications

References 46 publications

Design combinations of evolved phage and antibiotic for antibacterial guided by analyzing the phage resistance of poorly antimicrobial phage

Design combinations of evolved phage and antibiotic for antibacterial guided by analyzing the phage resistance of poorly antimicrobial phage

Bacteriophage–Antibiotic Combination Therapy against Pseudomonas aeruginosa

Spontaneous mutations in hlyD and tuf genes result in resistance of Dickeya solani IPO 2222 to phage ϕD5 but cause decreased bacterial fitness and virulence in planta

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