Pseudomonas aeruginosa Resists Phage Infection via Eavesdropping on Indole Signaling

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

doi:10.1128/spectrum.03911-22

Cited by 6 publications

(4 citation statements)

References 49 publications

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“…Studies show that many P. aeruginosa phages utilize pili as the primary receptor to infect cells, and mutations or inhibition of T4P synthesis may reduce the adsorption [ 18 , 40 , 41 , 46 , 47 ]. Downregulation of pilA , pilB and pilQ genes reduced T4P-mediated phage adsorption to protect P. aeruginosa from phage infection [ 41 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Quorum sensing gene lasR promotes phage vB_Pae_PLY infection in Pseudomonas aeruginosa

Liu,

Yao,

Mao

et al. 2024

BMC Microbiol

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Background Quorum sensing (QS) is a cell density-based intercellular communication system that controls virulence gene expression and biofilm formation. In Pseudomonas aeruginosa (P. aeruginosa), the LasR system sits at the top of the QS hierarchy and coordinates the expression of a series of important traits. However, the role of lasR in phage infection remains unclear. This study aims to investigate the role of lasR QS in phage infection. Methods The P. aeruginosa phage was isolated from sewage, and its biological characteristics and whole genome were analyzed. The adsorption receptor was identified via a phage adsorption assay. Following lasR gene knockout, the adsorption rate and bactericidal activity of phage were analyzed. Finally, real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to explore how lasR promoting phage infection. Results The lytic phage vB_Pae_PLY was isolated and lipopolysaccharide (LPS) was identified as its adsorption receptor. The adsorption rate and bactericidal activity of vB_Pae_PLY were reduced after lasR knockout. RT-qPCR results showed that the expression of galU, a key gene involved in LPS synthesis, was down-regulated, and several genes related to type IV pili (T4P) were also down-regulated in the lasR mutant PaΔlasR. Conclusions The study showed that QS lasR may promote phage vB_Pae_PLY infection by involving in the synthesis of LPS and T4P. This study provides an example of QS in promoting phage infection and deepens the understanding of phage-bacteria interactions.

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Section: Discussionmentioning

confidence: 99%

Quorum sensing gene lasR promotes phage vB_Pae_PLY infection in Pseudomonas aeruginosa

Liu,

Yao,

Mao

et al. 2024

BMC Microbiol

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“…Phage adsorption was observed by TEM as described previously ( Xuan et al., 2023a ). Briefly, P. aeruginosa cells were cultivated until reaching an optical density at 600 nm (OD 600nm ) of 2.5.…”

Section: Methodsmentioning

confidence: 99%

PqsA mutation-mediated enhancement of phage-mediated combat against Pseudomonas aeruginosa

Su,

Lu,

Kong

et al. 2024

Front. Cell. Infect. Microbiol.

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Phage therapy is a potential approach in the biocontrol of foodborne pathogens. However, the emergence of phage resistance and the narrow host range of most phage isolates continue to limit the antimicrobial efficacy of phages. Here, we investigated the potential of the pqsA gene, encoding the anthranilate-CoA ligase enzyme, as an adjuvant for phage therapy. The knockout of the pqsA gene significantly enhanced the bactericidal effect of phages vB_Pae_QDWS and vB_Pae_S1 against Pseudomonas aeruginosa. Under phage infection pressure, the growth of the PaΔpqsA was significantly inhibited within 8 h compared to the wild-type PAO1. Furthermore, we found that altering phage adsorption is not how PaΔpqsA responds to phage infection. Although pqsA represents a promising target for enhancing phage killing, it may not be applicable to all phages, such as types vB_Pae_W3 and vB_Pae_TR. Our findings provide new material reserves for the future design of novel phage-based therapeutic strategies.

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“…On the other hand, the phage host range is primarily restricted by receptors present on the surface of the host bacteria. Various structures on bacterial surfaces, such as outer membrane proteins, polysaccharides, teichoic acids, pili, flagella, and transporters, can act as bacterial receptors [23][24][25][26][27][28]. Much of the acquisition of phage resistance is attributable to mutations or deletions in receptor genes.…”

Section: Virology Of Phagesmentioning

confidence: 99%

Fitness Trade-Offs between Phage and Antibiotic Sensitivity in Phage-Resistant Variants: Molecular Action and Insights into Clinical Applications for Phage Therapy

Fujiki,

Nakamura,

Nakamura

et al. 2023

IJMS

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In recent decades, phage therapy has been overshadowed by the widespread use of antibiotics in Western countries. However, it has been revitalized as a powerful approach due to the increasing prevalence of antimicrobial-resistant bacteria. Although bacterial resistance to phages has been reported in clinical cases, recent studies on the fitness trade-offs between phage and antibiotic resistance have revealed new avenues in the field of phage therapy. This strategy aims to restore the antibiotic susceptibility of antimicrobial-resistant bacteria, even if phage-resistant variants develop. Here, we summarize the basic virological properties of phages and their applications within the context of antimicrobial resistance. In addition, we review the occurrence of phage resistance in clinical cases, and examine fitness trade-offs between phage and antibiotic sensitivity, exploring the potential of an evolutionary fitness cost as a countermeasure against phage resistance in therapy. Finally, we discuss future strategies and directions for phage-based therapy from the aspect of fitness trade-offs. This approach is expected to provide robust options when combined with antibiotics in this era of phage ‘re’-discovery.

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Pseudomonas aeruginosa Resists Phage Infection via Eavesdropping on Indole Signaling

Abstract: Our finding is significant with respect to the study of the interactions between phage and host. Although the important roles of indole in bacterial physiology have been revealed, no direct examples of indole participating in phage-host interactions were reported.

Cited by 6 publications

References 49 publications

Quorum sensing gene lasR promotes phage vB_Pae_PLY infection in Pseudomonas aeruginosa

Quorum sensing gene lasR promotes phage vB_Pae_PLY infection in Pseudomonas aeruginosa

PqsA mutation-mediated enhancement of phage-mediated combat against Pseudomonas aeruginosa

Fitness Trade-Offs between Phage and Antibiotic Sensitivity in Phage-Resistant Variants: Molecular Action and Insights into Clinical Applications for Phage Therapy

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