Essential Fitness Repertoire of Staphylococcus aureus during Co-infection with Acinetobacter baumannii
            <i>In Vivo</i>

Li, Gang; Shen, Wei; Gong, Yali; Li, Ming; Rao, Xiaocai; Liu, Qian; Yu, Yang; Zhou, Jing; Zhu, Keting; Yuan, Ming; Shang, Wenjun; Yang, Yi; Lu, Shuguang; Wang, Jing; Zhao, Yan

doi:10.1128/msystems.00338-22

Cited by 7 publications

(11 citation statements)

References 55 publications

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“…S. aureus is a notorious pathogen involved in polymicrobial biofilm infections, and its co-infections with A. baumannii or P. aeruginosa have been frequently reported [ 13 ]. Mixed-species biofilms of S. aureus and A. baumannii in diverse inoculation ratios (1:1, 10:1, and 100:1) were generated in 96-well plates for 24 h. LysSYL demonstrated the ability to disrupt dual-species biofilms of S. aureus USA300 and A. baumannii ATCC 19606 (1:1) in a dose-dependent manner, whereas 64×MIC of VAN (against S. aureus USA300) and MEM (against A. baumannii ATCC 19606) did not exhibit biofilm elimination effect (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, LysSYL effectively disrupted mixed-species biofilms formed by S. aureus and A. baumannii (Fig. 7 ), which is a common co-infection encountered in clinical practice [ 13 ]. However, LysSYL did not exhibit any effect on the disruption of mono-species biofilms generated by A. baumannii ATCC 19606 and the CRAB strain AB2 (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Statistics of 80.9% of microbial biofilm cases in venous catheter infections are associated with Acinetobacter baumannii , Staphylococcus spp., E. coli , and K. pneumoniae [ 12 ]. In addition, the co-infections caused by S. aureus and A. baumannii predominate in 760 collected clinical samples during 2017 to 2019 [ 13 ]. The polymicrobial infections not only are more virulent than single-species infections but also lead to a chronic stage of infection [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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LysSYL: a broad-spectrum phage endolysin targeting Staphylococcus species and eradicating S. aureus biofilms

Liu,

Wei,

Wang

et al. 2024

Microb Cell Fact

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Background Staphylococcus aureus and its single or mixed biofilm infections seriously threaten global public health. Phage therapy, which uses active phage particles or phage-derived endolysins, has emerged as a promising alternative strategy to antibiotic treatment. However, high-efficient phage therapeutic regimens have yet to be established. Results In this study, we used an enrichment procedure to isolate phages against methicillin-resistant S. aureus (MRSA) XN108. We characterized phage SYL, a new member of the Kayvirus genus, Herelleviridae family. The phage endolysin LysSYL was expressed. LysSYL demonstrated stability under various conditions and exhibited a broader range of efficacy against staphylococcal strains than its parent phage (100% vs. 41.7%). Moreover, dynamic live/dead bacterial observation demonstrated that LysSYL could completely lyse MRSA USA300 within 10 min. Scan and transmission electron microscopy revealed evident bacterial cell perforation and deformation. In addition, LysSYL displayed strong eradication activity against single- and mixed-species biofilms associated with S. aureus. It also had the ability to kill bacterial persisters, and proved highly effective in eliminating persistent S. aureus when combined with vancomycin. Furthermore, LysSYL protected BALB/c mice from lethal S. aureus infections. A single-dose treatment with 50 mg/kg of LysSYL resulted in a dramatic reduction in bacterial loads in the blood, liver, spleen, lungs, and kidneys of a peritonitis mouse model, which resulted in rescuing 100% of mice challenged with 108 colony forming units of S. aureus USA300. Conclusions Overall, the data provided in this study highlight the strong therapeutic potential of endolysin LysSYL in combating staphylococcal infections, including mono- and mixed-species biofilms related to S. aureus.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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LysSYL: a broad-spectrum phage endolysin targeting Staphylococcus species and eradicating S. aureus biofilms

Liu,

Wei,

Wang

et al. 2024

Microb Cell Fact

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“…LysSYL eliminates mixed-species bio lms associated with S. aureus S. aureus is a notorious pathogen involved in polymicrobial bio lm infections, and its co-infections with A. baumannii or P. aeruginosa have been frequently reported 12 . Mixed-species bio lms of S. aureus and A. baumannii in diverse inoculation ratios (1:1, 10:1, and 100:1) were generated in 96-well plates for 24 h. LysSYL demonstrated the ability to disrupt dual-species bio lms of S. aureus USA300 and A. baumannii ATCC 19606 (1:1) in a dose-dependent manner, whereas 64×MIC of VAN (against S. aureus USA300) and MEM (against A. baumannii ATCC 19606) did not exhibit bio lm elimination effect (Fig.…”

Section: Lyssyl Rapidly Disrupts S Aureus Cellsmentioning

confidence: 99%

“…S. aureus forms mono-species bio lms to evade host immune responses, and bio lm-encased staphylococcal cells can be 10-1000 times more resistant to conventional antibiotics than their planktonic counterparts 8,11 . Moreover, S. aureus is notorious for its ability to generate mixed-species bio lms with other MDR pathogens, such as carbapenem-resistance Acinetobacter baumannii (CRAB) and P. aeruginosa 12 . Therefore, the development of novel antimicrobial alternatives to control drug-resistant S. aureus infections is urgently needed.…”

Section: Introductionmentioning

confidence: 99%

A novel phage endolysin inactivates a wide range of Staphylococcus aureus and eliminates mono- and mixed-species biofilms associated with S. aureus

Rao,

Liu,

Wei

et al. 2023

Preprint

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Staphylococcus aureus and its single or mixed biofilm infections seriously threaten global public health. Phage therapy, which uses active particles or phage-derived endolysins, has emerged as a promising alternative strategy to antibiotic treatment. However, high-efficient phage therapeutic regimens have yet to be established. In this study, we used a mixed-sample procedure to isolate phages against methicillin-resistant S. aureus (MRSA) XN108. We characterized a new phage, SYL, sequenced its genomes, and engineered its novel endolysin, LysSYL. LysSYL demonstrated stability under various conditions and exhibited a broader range of efficacy against staphylococcal strains than its parent phage (100% vs. 41.7%). Moreover, dynamic live/dead bacterial observation demonstrated that LysSYL could completely inactivate MRSA USA300 within 10 min. Scan and transmission electron microscopy revealed evident bacterial cell perforation and deformation. In addition, LysSYL displayed strong eradication activity against single- and mixed-species biofilms associated with S. aureus. It also had the ability to disrupt bacterial persisters, and it proved highly effective in eliminating persistent S. aureus when combined with vancomycin. Furthermore, LysSYL protected BALB/c mice from lethal S. aureus infections. A single-dose treatment with 50 mg/kg of LysSYL resulted in a dramatic reduction in bacterial loads in the blood, liver, spleen, lungs, and kidneys of a peritonitis mouse model, which resulted in rescuing 100% of mice challenged with 108 colony forming units of S. aureus USA300. Overall, the data provided in this study highlight the strong therapeutic potential of endolysin LysSYL in combating staphylococcal infections, including mono- and mixed-species biofilms related to S. aureus.

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SeqKit2: A Swiss army knife for sequence and alignment processing

Shen,

Sipos,

Zhao

2024

iMeta

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In the era of ubiquitous high‐throughput sequencing studies, there is a growing need for analysis tools that are not just performant but also comprehensive and user‐friendly enough to cater to both novice and advanced users. This article introduces SeqKit2, the next iteration of the widely used sequence analysis tool SeqKit, featuring expanded functionality, performance optimizations, and support for additional compression methods. Retaining a pragmatic subcommand architecture, SeqKit2 represents substantial enhancement through the inclusion of 19 additional subcommands, expanding its overall repertoire to a total of 38 in eight categories. The new subcommands add functionality such as amplicon processing and robust, error‐tolerant parsing of sequence records. In addition, three subcommands designed for real‐time analysis are added for periodic monitoring of properties of FASTQ and Binary Alignment/Map alignment records and real‐time streaming from multiple sequence files. The performance of SeqKit2 is benchmarked against the old version of SeqKit, Bioawk, Seqtk, and SeqFu tools. SeqKit2 consistently outperforms its predecessor, albeit with marginally higher memory usage, while maintaining competitive runtimes against other tools. With its broad functionality, proven usability, and ongoing development driven by user feedback, we hope that bioinformaticians will find SeqKit2 useful as a “Swiss army knife” of sequence and alignment processing—equally adept at facilitating ad hoc analyses and seamlessly integrating into larger pipelines.

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Essential Fitness Repertoire of Staphylococcus aureus during Co-infection with Acinetobacter baumannii In Vivo

Cited by 7 publications

References 55 publications

LysSYL: a broad-spectrum phage endolysin targeting Staphylococcus species and eradicating S. aureus biofilms

LysSYL: a broad-spectrum phage endolysin targeting Staphylococcus species and eradicating S. aureus biofilms

A novel phage endolysin inactivates a wide range of Staphylococcus aureus and eliminates mono- and mixed-species biofilms associated with S. aureus

SeqKit2: A Swiss army knife for sequence and alignment processing

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