Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa

ABSTRACT The emergence and spread of antibiotic resistance pose serious environmental and health challenges. Attention has been drawn to phage therapy as an alternative approach to combat antibiotic resistance with immense potential. However, one of the obstacles to phage therapy is phage resistance, and it can be acquired through genetic mutations, followed by consequences of phenotypic variations. Therefore, understanding the mechanisms underlying phage-host interactions will provide us with greater detail on how to optimize phage therapy. In this study, three lytic phages (phipa2, phipa4, and phipa10) were isolated to investigate phage resistance and the potential fitness trade-offs in Pseudomonas aeruginosa. Specifically, in phage-resistant mutants phipa2-R and phipa4-R, mutations in conferring resistance occurred in genes pilT and pilB, both essential for type IV pili (T4P) biosynthesis. In the phage-resistant mutant phipa10-R, a large chromosomal deletion of ~294 kb, including the hmgA (homogentisate 1,2-dioxygenase) and galU (UTP–glucose-1-phosphate uridylyltransferase) genes, was observed and conferred phage phipa10 resistance. Further, we show examples of associated trade-offs in these phage-resistant mutations, e.g., impaired motility, reduced biofilm formation, and increased antibiotic susceptibility. Collectively, our study sheds light on resistance-mediated genetic mutations and their pleiotropic phenotypes, further emphasizing the impressive complexity and diversity of phage-host interactions and the challenges they pose when controlling bacterial diseases in this important pathogen. IMPORTANCE Battling phage resistance is one of the main challenges faced by phage therapy. To overcome this challenge, detailed information about the mechanisms of phage-host interactions is required to understand the bacterial evolutionary processes. In this study, we identified mutations in key steps of type IV pili (T4P) and O-antigen biosynthesis leading to phage resistance and provided new evidence on how phage predation contributed toward host phenotypes and fitness variations. Together, our results add further fundamental knowledge on phage-host interactions and how they regulate different aspects of Pseudomonas cell behaviors. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Na Li [verfasserIn] Yigang Zeng [verfasserIn] Mengran Wang [verfasserIn] Rong Bao [verfasserIn] Yu Chen [verfasserIn] Xiaoyu Li [verfasserIn] Jue Pan [verfasserIn] Tongyu Zhu [verfasserIn] Bijie Hu [verfasserIn] Demeng Tan [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	phage resistance phage-host interactions Pseudomonas aeruginosa phage therapy

Übergeordnetes Werk:	In: Microbiology Spectrum - American Society for Microbiology, 2022, 10(2022), 5
Übergeordnetes Werk:	volume:10 ; year:2022 ; number:5

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1128/spectrum.02072-22

Katalog-ID:	DOAJ003260062

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allfields	10.1128/spectrum.02072-22 doi (DE-627)DOAJ003260062 (DE-599)DOAJ016624a1683e41c1a98724a121bd782a DE-627 ger DE-627 rakwb eng QR1-502 Na Li verfasserin aut Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT The emergence and spread of antibiotic resistance pose serious environmental and health challenges. Attention has been drawn to phage therapy as an alternative approach to combat antibiotic resistance with immense potential. However, one of the obstacles to phage therapy is phage resistance, and it can be acquired through genetic mutations, followed by consequences of phenotypic variations. Therefore, understanding the mechanisms underlying phage-host interactions will provide us with greater detail on how to optimize phage therapy. In this study, three lytic phages (phipa2, phipa4, and phipa10) were isolated to investigate phage resistance and the potential fitness trade-offs in Pseudomonas aeruginosa. Specifically, in phage-resistant mutants phipa2-R and phipa4-R, mutations in conferring resistance occurred in genes pilT and pilB, both essential for type IV pili (T4P) biosynthesis. In the phage-resistant mutant phipa10-R, a large chromosomal deletion of ~294 kb, including the hmgA (homogentisate 1,2-dioxygenase) and galU (UTP–glucose-1-phosphate uridylyltransferase) genes, was observed and conferred phage phipa10 resistance. Further, we show examples of associated trade-offs in these phage-resistant mutations, e.g., impaired motility, reduced biofilm formation, and increased antibiotic susceptibility. Collectively, our study sheds light on resistance-mediated genetic mutations and their pleiotropic phenotypes, further emphasizing the impressive complexity and diversity of phage-host interactions and the challenges they pose when controlling bacterial diseases in this important pathogen. IMPORTANCE Battling phage resistance is one of the main challenges faced by phage therapy. To overcome this challenge, detailed information about the mechanisms of phage-host interactions is required to understand the bacterial evolutionary processes. In this study, we identified mutations in key steps of type IV pili (T4P) and O-antigen biosynthesis leading to phage resistance and provided new evidence on how phage predation contributed toward host phenotypes and fitness variations. Together, our results add further fundamental knowledge on phage-host interactions and how they regulate different aspects of Pseudomonas cell behaviors. phage resistance phage-host interactions Pseudomonas aeruginosa phage therapy Microbiology Yigang Zeng verfasserin aut Mengran Wang verfasserin aut Rong Bao verfasserin aut Yu Chen verfasserin aut Xiaoyu Li verfasserin aut Jue Pan verfasserin aut Tongyu Zhu verfasserin aut Bijie Hu verfasserin aut Demeng Tan verfasserin aut In Microbiology Spectrum American Society for Microbiology, 2022 10(2022), 5 (DE-627)816693293 (DE-600)2807133-5 21650497 nnns volume:10 year:2022 number:5 https://doi.org/10.1128/spectrum.02072-22 kostenfrei https://doaj.org/article/016624a1683e41c1a98724a121bd782a kostenfrei https://journals.asm.org/doi/10.1128/spectrum.02072-22 kostenfrei https://doaj.org/toc/2165-0497 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 5
spelling	10.1128/spectrum.02072-22 doi (DE-627)DOAJ003260062 (DE-599)DOAJ016624a1683e41c1a98724a121bd782a DE-627 ger DE-627 rakwb eng QR1-502 Na Li verfasserin aut Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT The emergence and spread of antibiotic resistance pose serious environmental and health challenges. Attention has been drawn to phage therapy as an alternative approach to combat antibiotic resistance with immense potential. However, one of the obstacles to phage therapy is phage resistance, and it can be acquired through genetic mutations, followed by consequences of phenotypic variations. Therefore, understanding the mechanisms underlying phage-host interactions will provide us with greater detail on how to optimize phage therapy. In this study, three lytic phages (phipa2, phipa4, and phipa10) were isolated to investigate phage resistance and the potential fitness trade-offs in Pseudomonas aeruginosa. Specifically, in phage-resistant mutants phipa2-R and phipa4-R, mutations in conferring resistance occurred in genes pilT and pilB, both essential for type IV pili (T4P) biosynthesis. In the phage-resistant mutant phipa10-R, a large chromosomal deletion of ~294 kb, including the hmgA (homogentisate 1,2-dioxygenase) and galU (UTP–glucose-1-phosphate uridylyltransferase) genes, was observed and conferred phage phipa10 resistance. Further, we show examples of associated trade-offs in these phage-resistant mutations, e.g., impaired motility, reduced biofilm formation, and increased antibiotic susceptibility. Collectively, our study sheds light on resistance-mediated genetic mutations and their pleiotropic phenotypes, further emphasizing the impressive complexity and diversity of phage-host interactions and the challenges they pose when controlling bacterial diseases in this important pathogen. IMPORTANCE Battling phage resistance is one of the main challenges faced by phage therapy. To overcome this challenge, detailed information about the mechanisms of phage-host interactions is required to understand the bacterial evolutionary processes. In this study, we identified mutations in key steps of type IV pili (T4P) and O-antigen biosynthesis leading to phage resistance and provided new evidence on how phage predation contributed toward host phenotypes and fitness variations. Together, our results add further fundamental knowledge on phage-host interactions and how they regulate different aspects of Pseudomonas cell behaviors. phage resistance phage-host interactions Pseudomonas aeruginosa phage therapy Microbiology Yigang Zeng verfasserin aut Mengran Wang verfasserin aut Rong Bao verfasserin aut Yu Chen verfasserin aut Xiaoyu Li verfasserin aut Jue Pan verfasserin aut Tongyu Zhu verfasserin aut Bijie Hu verfasserin aut Demeng Tan verfasserin aut In Microbiology Spectrum American Society for Microbiology, 2022 10(2022), 5 (DE-627)816693293 (DE-600)2807133-5 21650497 nnns volume:10 year:2022 number:5 https://doi.org/10.1128/spectrum.02072-22 kostenfrei https://doaj.org/article/016624a1683e41c1a98724a121bd782a kostenfrei https://journals.asm.org/doi/10.1128/spectrum.02072-22 kostenfrei https://doaj.org/toc/2165-0497 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 5
allfields_unstemmed	10.1128/spectrum.02072-22 doi (DE-627)DOAJ003260062 (DE-599)DOAJ016624a1683e41c1a98724a121bd782a DE-627 ger DE-627 rakwb eng QR1-502 Na Li verfasserin aut Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT The emergence and spread of antibiotic resistance pose serious environmental and health challenges. Attention has been drawn to phage therapy as an alternative approach to combat antibiotic resistance with immense potential. However, one of the obstacles to phage therapy is phage resistance, and it can be acquired through genetic mutations, followed by consequences of phenotypic variations. Therefore, understanding the mechanisms underlying phage-host interactions will provide us with greater detail on how to optimize phage therapy. In this study, three lytic phages (phipa2, phipa4, and phipa10) were isolated to investigate phage resistance and the potential fitness trade-offs in Pseudomonas aeruginosa. Specifically, in phage-resistant mutants phipa2-R and phipa4-R, mutations in conferring resistance occurred in genes pilT and pilB, both essential for type IV pili (T4P) biosynthesis. In the phage-resistant mutant phipa10-R, a large chromosomal deletion of ~294 kb, including the hmgA (homogentisate 1,2-dioxygenase) and galU (UTP–glucose-1-phosphate uridylyltransferase) genes, was observed and conferred phage phipa10 resistance. Further, we show examples of associated trade-offs in these phage-resistant mutations, e.g., impaired motility, reduced biofilm formation, and increased antibiotic susceptibility. Collectively, our study sheds light on resistance-mediated genetic mutations and their pleiotropic phenotypes, further emphasizing the impressive complexity and diversity of phage-host interactions and the challenges they pose when controlling bacterial diseases in this important pathogen. IMPORTANCE Battling phage resistance is one of the main challenges faced by phage therapy. To overcome this challenge, detailed information about the mechanisms of phage-host interactions is required to understand the bacterial evolutionary processes. In this study, we identified mutations in key steps of type IV pili (T4P) and O-antigen biosynthesis leading to phage resistance and provided new evidence on how phage predation contributed toward host phenotypes and fitness variations. Together, our results add further fundamental knowledge on phage-host interactions and how they regulate different aspects of Pseudomonas cell behaviors. phage resistance phage-host interactions Pseudomonas aeruginosa phage therapy Microbiology Yigang Zeng verfasserin aut Mengran Wang verfasserin aut Rong Bao verfasserin aut Yu Chen verfasserin aut Xiaoyu Li verfasserin aut Jue Pan verfasserin aut Tongyu Zhu verfasserin aut Bijie Hu verfasserin aut Demeng Tan verfasserin aut In Microbiology Spectrum American Society for Microbiology, 2022 10(2022), 5 (DE-627)816693293 (DE-600)2807133-5 21650497 nnns volume:10 year:2022 number:5 https://doi.org/10.1128/spectrum.02072-22 kostenfrei https://doaj.org/article/016624a1683e41c1a98724a121bd782a kostenfrei https://journals.asm.org/doi/10.1128/spectrum.02072-22 kostenfrei https://doaj.org/toc/2165-0497 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 5
allfieldsGer	10.1128/spectrum.02072-22 doi (DE-627)DOAJ003260062 (DE-599)DOAJ016624a1683e41c1a98724a121bd782a DE-627 ger DE-627 rakwb eng QR1-502 Na Li verfasserin aut Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT The emergence and spread of antibiotic resistance pose serious environmental and health challenges. Attention has been drawn to phage therapy as an alternative approach to combat antibiotic resistance with immense potential. However, one of the obstacles to phage therapy is phage resistance, and it can be acquired through genetic mutations, followed by consequences of phenotypic variations. Therefore, understanding the mechanisms underlying phage-host interactions will provide us with greater detail on how to optimize phage therapy. In this study, three lytic phages (phipa2, phipa4, and phipa10) were isolated to investigate phage resistance and the potential fitness trade-offs in Pseudomonas aeruginosa. Specifically, in phage-resistant mutants phipa2-R and phipa4-R, mutations in conferring resistance occurred in genes pilT and pilB, both essential for type IV pili (T4P) biosynthesis. In the phage-resistant mutant phipa10-R, a large chromosomal deletion of ~294 kb, including the hmgA (homogentisate 1,2-dioxygenase) and galU (UTP–glucose-1-phosphate uridylyltransferase) genes, was observed and conferred phage phipa10 resistance. Further, we show examples of associated trade-offs in these phage-resistant mutations, e.g., impaired motility, reduced biofilm formation, and increased antibiotic susceptibility. Collectively, our study sheds light on resistance-mediated genetic mutations and their pleiotropic phenotypes, further emphasizing the impressive complexity and diversity of phage-host interactions and the challenges they pose when controlling bacterial diseases in this important pathogen. IMPORTANCE Battling phage resistance is one of the main challenges faced by phage therapy. To overcome this challenge, detailed information about the mechanisms of phage-host interactions is required to understand the bacterial evolutionary processes. In this study, we identified mutations in key steps of type IV pili (T4P) and O-antigen biosynthesis leading to phage resistance and provided new evidence on how phage predation contributed toward host phenotypes and fitness variations. Together, our results add further fundamental knowledge on phage-host interactions and how they regulate different aspects of Pseudomonas cell behaviors. phage resistance phage-host interactions Pseudomonas aeruginosa phage therapy Microbiology Yigang Zeng verfasserin aut Mengran Wang verfasserin aut Rong Bao verfasserin aut Yu Chen verfasserin aut Xiaoyu Li verfasserin aut Jue Pan verfasserin aut Tongyu Zhu verfasserin aut Bijie Hu verfasserin aut Demeng Tan verfasserin aut In Microbiology Spectrum American Society for Microbiology, 2022 10(2022), 5 (DE-627)816693293 (DE-600)2807133-5 21650497 nnns volume:10 year:2022 number:5 https://doi.org/10.1128/spectrum.02072-22 kostenfrei https://doaj.org/article/016624a1683e41c1a98724a121bd782a kostenfrei https://journals.asm.org/doi/10.1128/spectrum.02072-22 kostenfrei https://doaj.org/toc/2165-0497 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 5
allfieldsSound	10.1128/spectrum.02072-22 doi (DE-627)DOAJ003260062 (DE-599)DOAJ016624a1683e41c1a98724a121bd782a DE-627 ger DE-627 rakwb eng QR1-502 Na Li verfasserin aut Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT The emergence and spread of antibiotic resistance pose serious environmental and health challenges. Attention has been drawn to phage therapy as an alternative approach to combat antibiotic resistance with immense potential. However, one of the obstacles to phage therapy is phage resistance, and it can be acquired through genetic mutations, followed by consequences of phenotypic variations. Therefore, understanding the mechanisms underlying phage-host interactions will provide us with greater detail on how to optimize phage therapy. In this study, three lytic phages (phipa2, phipa4, and phipa10) were isolated to investigate phage resistance and the potential fitness trade-offs in Pseudomonas aeruginosa. Specifically, in phage-resistant mutants phipa2-R and phipa4-R, mutations in conferring resistance occurred in genes pilT and pilB, both essential for type IV pili (T4P) biosynthesis. In the phage-resistant mutant phipa10-R, a large chromosomal deletion of ~294 kb, including the hmgA (homogentisate 1,2-dioxygenase) and galU (UTP–glucose-1-phosphate uridylyltransferase) genes, was observed and conferred phage phipa10 resistance. Further, we show examples of associated trade-offs in these phage-resistant mutations, e.g., impaired motility, reduced biofilm formation, and increased antibiotic susceptibility. Collectively, our study sheds light on resistance-mediated genetic mutations and their pleiotropic phenotypes, further emphasizing the impressive complexity and diversity of phage-host interactions and the challenges they pose when controlling bacterial diseases in this important pathogen. IMPORTANCE Battling phage resistance is one of the main challenges faced by phage therapy. To overcome this challenge, detailed information about the mechanisms of phage-host interactions is required to understand the bacterial evolutionary processes. In this study, we identified mutations in key steps of type IV pili (T4P) and O-antigen biosynthesis leading to phage resistance and provided new evidence on how phage predation contributed toward host phenotypes and fitness variations. Together, our results add further fundamental knowledge on phage-host interactions and how they regulate different aspects of Pseudomonas cell behaviors. phage resistance phage-host interactions Pseudomonas aeruginosa phage therapy Microbiology Yigang Zeng verfasserin aut Mengran Wang verfasserin aut Rong Bao verfasserin aut Yu Chen verfasserin aut Xiaoyu Li verfasserin aut Jue Pan verfasserin aut Tongyu Zhu verfasserin aut Bijie Hu verfasserin aut Demeng Tan verfasserin aut In Microbiology Spectrum American Society for Microbiology, 2022 10(2022), 5 (DE-627)816693293 (DE-600)2807133-5 21650497 nnns volume:10 year:2022 number:5 https://doi.org/10.1128/spectrum.02072-22 kostenfrei https://doaj.org/article/016624a1683e41c1a98724a121bd782a kostenfrei https://journals.asm.org/doi/10.1128/spectrum.02072-22 kostenfrei https://doaj.org/toc/2165-0497 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 5
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authorswithroles_txt_mv	Na Li @@aut@@ Yigang Zeng @@aut@@ Mengran Wang @@aut@@ Rong Bao @@aut@@ Yu Chen @@aut@@ Xiaoyu Li @@aut@@ Jue Pan @@aut@@ Tongyu Zhu @@aut@@ Bijie Hu @@aut@@ Demeng Tan @@aut@@
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spellingShingle	Na Li misc QR1-502 misc phage resistance misc phage-host interactions misc Pseudomonas aeruginosa misc phage therapy misc Microbiology Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa
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topic_title	QR1-502 Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa phage resistance phage-host interactions Pseudomonas aeruginosa phage therapy
topic	misc QR1-502 misc phage resistance misc phage-host interactions misc Pseudomonas aeruginosa misc phage therapy misc Microbiology
topic_unstemmed	misc QR1-502 misc phage resistance misc phage-host interactions misc Pseudomonas aeruginosa misc phage therapy misc Microbiology
topic_browse	misc QR1-502 misc phage resistance misc phage-host interactions misc Pseudomonas aeruginosa misc phage therapy misc Microbiology
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title	Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa
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title_full	Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa
author_sort	Na Li
journal	Microbiology Spectrum
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author_browse	Na Li Yigang Zeng Mengran Wang Rong Bao Yu Chen Xiaoyu Li Jue Pan Tongyu Zhu Bijie Hu Demeng Tan
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title_sort	characterization of phage resistance and their impacts on bacterial fitness in pseudomonas aeruginosa
callnumber	QR1-502
title_auth	Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa
abstract	ABSTRACT The emergence and spread of antibiotic resistance pose serious environmental and health challenges. Attention has been drawn to phage therapy as an alternative approach to combat antibiotic resistance with immense potential. However, one of the obstacles to phage therapy is phage resistance, and it can be acquired through genetic mutations, followed by consequences of phenotypic variations. Therefore, understanding the mechanisms underlying phage-host interactions will provide us with greater detail on how to optimize phage therapy. In this study, three lytic phages (phipa2, phipa4, and phipa10) were isolated to investigate phage resistance and the potential fitness trade-offs in Pseudomonas aeruginosa. Specifically, in phage-resistant mutants phipa2-R and phipa4-R, mutations in conferring resistance occurred in genes pilT and pilB, both essential for type IV pili (T4P) biosynthesis. In the phage-resistant mutant phipa10-R, a large chromosomal deletion of ~294 kb, including the hmgA (homogentisate 1,2-dioxygenase) and galU (UTP–glucose-1-phosphate uridylyltransferase) genes, was observed and conferred phage phipa10 resistance. Further, we show examples of associated trade-offs in these phage-resistant mutations, e.g., impaired motility, reduced biofilm formation, and increased antibiotic susceptibility. Collectively, our study sheds light on resistance-mediated genetic mutations and their pleiotropic phenotypes, further emphasizing the impressive complexity and diversity of phage-host interactions and the challenges they pose when controlling bacterial diseases in this important pathogen. IMPORTANCE Battling phage resistance is one of the main challenges faced by phage therapy. To overcome this challenge, detailed information about the mechanisms of phage-host interactions is required to understand the bacterial evolutionary processes. In this study, we identified mutations in key steps of type IV pili (T4P) and O-antigen biosynthesis leading to phage resistance and provided new evidence on how phage predation contributed toward host phenotypes and fitness variations. Together, our results add further fundamental knowledge on phage-host interactions and how they regulate different aspects of Pseudomonas cell behaviors.
abstractGer	ABSTRACT The emergence and spread of antibiotic resistance pose serious environmental and health challenges. Attention has been drawn to phage therapy as an alternative approach to combat antibiotic resistance with immense potential. However, one of the obstacles to phage therapy is phage resistance, and it can be acquired through genetic mutations, followed by consequences of phenotypic variations. Therefore, understanding the mechanisms underlying phage-host interactions will provide us with greater detail on how to optimize phage therapy. In this study, three lytic phages (phipa2, phipa4, and phipa10) were isolated to investigate phage resistance and the potential fitness trade-offs in Pseudomonas aeruginosa. Specifically, in phage-resistant mutants phipa2-R and phipa4-R, mutations in conferring resistance occurred in genes pilT and pilB, both essential for type IV pili (T4P) biosynthesis. In the phage-resistant mutant phipa10-R, a large chromosomal deletion of ~294 kb, including the hmgA (homogentisate 1,2-dioxygenase) and galU (UTP–glucose-1-phosphate uridylyltransferase) genes, was observed and conferred phage phipa10 resistance. Further, we show examples of associated trade-offs in these phage-resistant mutations, e.g., impaired motility, reduced biofilm formation, and increased antibiotic susceptibility. Collectively, our study sheds light on resistance-mediated genetic mutations and their pleiotropic phenotypes, further emphasizing the impressive complexity and diversity of phage-host interactions and the challenges they pose when controlling bacterial diseases in this important pathogen. IMPORTANCE Battling phage resistance is one of the main challenges faced by phage therapy. To overcome this challenge, detailed information about the mechanisms of phage-host interactions is required to understand the bacterial evolutionary processes. In this study, we identified mutations in key steps of type IV pili (T4P) and O-antigen biosynthesis leading to phage resistance and provided new evidence on how phage predation contributed toward host phenotypes and fitness variations. Together, our results add further fundamental knowledge on phage-host interactions and how they regulate different aspects of Pseudomonas cell behaviors.
abstract_unstemmed	ABSTRACT The emergence and spread of antibiotic resistance pose serious environmental and health challenges. Attention has been drawn to phage therapy as an alternative approach to combat antibiotic resistance with immense potential. However, one of the obstacles to phage therapy is phage resistance, and it can be acquired through genetic mutations, followed by consequences of phenotypic variations. Therefore, understanding the mechanisms underlying phage-host interactions will provide us with greater detail on how to optimize phage therapy. In this study, three lytic phages (phipa2, phipa4, and phipa10) were isolated to investigate phage resistance and the potential fitness trade-offs in Pseudomonas aeruginosa. Specifically, in phage-resistant mutants phipa2-R and phipa4-R, mutations in conferring resistance occurred in genes pilT and pilB, both essential for type IV pili (T4P) biosynthesis. In the phage-resistant mutant phipa10-R, a large chromosomal deletion of ~294 kb, including the hmgA (homogentisate 1,2-dioxygenase) and galU (UTP–glucose-1-phosphate uridylyltransferase) genes, was observed and conferred phage phipa10 resistance. Further, we show examples of associated trade-offs in these phage-resistant mutations, e.g., impaired motility, reduced biofilm formation, and increased antibiotic susceptibility. Collectively, our study sheds light on resistance-mediated genetic mutations and their pleiotropic phenotypes, further emphasizing the impressive complexity and diversity of phage-host interactions and the challenges they pose when controlling bacterial diseases in this important pathogen. IMPORTANCE Battling phage resistance is one of the main challenges faced by phage therapy. To overcome this challenge, detailed information about the mechanisms of phage-host interactions is required to understand the bacterial evolutionary processes. In this study, we identified mutations in key steps of type IV pili (T4P) and O-antigen biosynthesis leading to phage resistance and provided new evidence on how phage predation contributed toward host phenotypes and fitness variations. Together, our results add further fundamental knowledge on phage-host interactions and how they regulate different aspects of Pseudomonas cell behaviors.
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title_short	Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa
url	https://doi.org/10.1128/spectrum.02072-22 https://doaj.org/article/016624a1683e41c1a98724a121bd782a https://journals.asm.org/doi/10.1128/spectrum.02072-22 https://doaj.org/toc/2165-0497
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author2	Yigang Zeng Mengran Wang Rong Bao Yu Chen Xiaoyu Li Jue Pan Tongyu Zhu Bijie Hu Demeng Tan
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