PAAR Proteins Are Versatile Clips That Enrich the Antimicrobial Weapon Arsenals of Prokaryotes

Zhang, Zheng; Liu, Ya; Zhang, Peng; Wang, Jianing; Li, Dandan; Li, Yuezhong

doi:10.1128/msystems.00953-21

Cited by 12 publications

(11 citation statements)

References 47 publications

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“…At the tip of the spear, PAAR-repeat proteins have been recognized as an important carrier for toxic effectors ( 19 ) or directly as toxins for those PAARs with extended N- or C-terminal domains ( 20 , 21 ). A recent study has done an extensive search for PAAR homologs in the NCBI RefSeq database ( 22 ), and the results are consistent with previous findings ( 20 ). A greater number of PAAR proteins (47,625 homologs) have been found, and it is estimated that 23% of bacterial genomes encode at least one PAAR gene, which is in general agreement with the distribution of T6SS in bacteria.…”

Section: Commentarysupporting

confidence: 87%

“…A greater number of PAAR proteins (47,625 homologs) have been found, and it is estimated that 23% of bacterial genomes encode at least one PAAR gene, which is in general agreement with the distribution of T6SS in bacteria. Although it is known that genomes commonly contain multiple copies of PAAR genes, it is astounding that 35 copies are found in the strain Chondromyces apiculatus DSM 436 ( 22 ). There is also a strong positive correlation between PAAR and vgrG genes.…”

Section: Commentarymentioning

confidence: 99%

“…There is also a strong positive correlation between PAAR and vgrG genes. Having learned the 35 copies of PAAR , one should be less surprised that C. apiculatus DSM 436 also carries 54 copies of vgrG ( 22 ). In addition, there are 1,300 PAAR-associated toxin-encoding genes, of which 40% are PAAR proteins with extended domains and the majority are predicted nucleases ( 22 ).…”

Section: Commentarymentioning

confidence: 99%

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More Than Just a Spearhead: Diverse Functions of PAAR for Assembly and Delivery of Toxins of the Contractile Injection Systems

2021

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Section: Commentarysupporting

confidence: 87%

Section: Commentarymentioning

confidence: 99%

Section: Commentarymentioning

confidence: 99%

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More Than Just a Spearhead: Diverse Functions of PAAR for Assembly and Delivery of Toxins of the Contractile Injection Systems

2021

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“…Multiple sequence alignment of the isolates’ Tse7 PAO1 (PA0099) homologs revealed lengths ranging from 315 to 386 aa ( Figure 10B ). All 22 homologs were predicted to possess the PAAR-like domain DUF4150 (PF13665) in their N-terminus, classifying them as PAAR subtype E2 ( Zhang et al, 2021 ). Alignment of the 22 homologous CTs confirmed 20 possessed the Tox-GHH2 domain (PF15635) in their CT ( Pissaridou et al, 2018 ), however, two tse7 homologs, PALA35_00106 and PALA37_02114 , did not ( Figure 10B ).…”

Section: Resultsmentioning

confidence: 99%

Diversity and prevalence of type VI secretion system effectors in clinical Pseudomonas aeruginosa isolates

et al. 2023

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Pseudomonas aeruginosa is an opportunistic pathogen and a major driver of morbidity and mortality in people with Cystic Fibrosis (CF). The Type VI secretion system (T6SS) is a molecular nanomachine that translocates effectors across the bacterial membrane into target cells or the extracellular environment enabling intermicrobial interaction. P. aeruginosa encodes three T6SS clusters, the H1-, H2- and H3-T6SS, and numerous orphan islands. Genetic diversity of T6SS-associated effectors in P. aeruginosa has been noted in reference strains but has yet to be explored in clinical isolates. Here, we perform a comprehensive bioinformatic analysis of the pangenome and T6SS effector genes in 52 high-quality clinical P. aeruginosa genomes isolated from CF patients and housed in the Personalised Approach to P. aeruginosa strain repository. We confirm that the clinical CF isolate pangenome is open and principally made up of accessory and unique genes that may provide strain-specific advantages. We observed genetic variability in some effector/immunity encoding genes and show that several well-characterised vgrG and PAAR islands are absent from numerous isolates. Our analysis shows clear evidence of disruption to T6SS genomic loci through transposon, prophage, and mobile genetic element insertions. We identified an orphan vgrG island in P. aeruginosa strain PAK and five clinical isolates using in silico analysis which we denote vgrG7, predicting a gene within this cluster to encode a Tle2 lipase family effector. Close comparison of T6SS loci in clinical isolates compared to reference P. aeruginosa strain PAO1 revealed the presence of genes encoding eight new T6SS effectors with the following putative functions: cytidine deaminase, lipase, metallopeptidase, NADase, and pyocin. Finally, the prevalence of characterised and putative T6SS effectors were assessed in 532 publicly available P. aeruginosa genomes, which suggests the existence of accessory effectors. Our in silico study of the P. aeruginosa T6SS exposes a level of genetic diversity at T6SS genomic loci not seen to date within P. aeruginosa, particularly in CF isolates. As understanding the effector repertoire is key to identifying the targets of T6SSs and its efficacy, this comprehensive analysis provides a path for future experimental characterisation of these mediators of intermicrobial competition and host manipulation.

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“…PAT resources have already been used in the prediction and identification of prokaryotic antimicrobial toxins ( 8 , 19 , 20 , 58 ). In the future, the PAT database will continue to integrate the latest knowledge of antimicrobial toxins to satisfy the needs of users worldwide, helping to promote efficient investigation on functions of antimicrobial toxins, the discovery of novel antimicrobial toxins, and an improved understanding of their biological roles and significance.…”

Section: Discussionmentioning

confidence: 99%

PAT: a comprehensive database of prokaryotic antimicrobial toxins

Liu

Pan

et al. 2022

Nucleic Acids Research

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Antimicrobial toxins help prokaryotes win competitive advantages in intraspecific or interspecific conflicts and are also a critical factor affecting the pathogenicity of many pathogens that threaten human health. Although many studies have revealed that antagonism based on antimicrobial toxins plays a central role in prokaryotic life, a database on antimicrobial toxins remains lacking. Here, we present the prokaryotic antimicrobial toxin database (PAT, http://bioinfo.qd.sdu.edu.cn/PAT/), a comprehensive data resource collection on experimentally validated antimicrobial toxins. PAT has organized information, derived from the reported literature, on antimicrobial toxins, as well as the corresponding immunity proteins, delivery mechanisms, toxin activities, structural characteristics, sequences, etc. Moreover, we also predict potential antimicrobial toxins in prokaryotic reference genomes and show the taxonomic information and environmental distribution of typical antimicrobial toxins. These details have been fully incorporated into the PAT database, where users can browse, search, download, analyse and view informative statistics and detailed information. PAT resources have already been used in our prediction and identification of prokaryotic antimicrobial toxins and may contribute to promoting the efficient investigation of antimicrobial toxin functions, the discovery of novel antimicrobial toxins, and an improved understanding of the biological roles and significance of these toxins.

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PAAR Proteins Are Versatile Clips That Enrich the Antimicrobial Weapon Arsenals of Prokaryotes

Abstract: Infectious diseases caused by microbial pathogens are severe threats to human health and economic development. To respond to these threats, it is necessary to understand how microorganisms survive in and adapt to complex environments.

Cited by 12 publications

References 47 publications

More Than Just a Spearhead: Diverse Functions of PAAR for Assembly and Delivery of Toxins of the Contractile Injection Systems

More Than Just a Spearhead: Diverse Functions of PAAR for Assembly and Delivery of Toxins of the Contractile Injection Systems

Diversity and prevalence of type VI secretion system effectors in clinical Pseudomonas aeruginosa isolates

PAT: a comprehensive database of prokaryotic antimicrobial toxins

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