Bacteria use structural imperfect mimicry to hijack the host interactome

Groot, Natalia Sánchez de; Torrent, M. C.

doi:10.1371/journal.pcbi.1008395

Cited by 11 publications

(12 citation statements)

References 60 publications

(68 reference statements)

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“…Indeed, the interfaces detected in human-binding partners correspond to interfaces predicted in other human–human interactions already described. These results suggest that the interactions detected by our pipelines are probably real and correspond to some kind of interface mimicry by pathogens [ 41 ].…”

Section: Resultsmentioning

confidence: 98%

Analysis of Host–Bacteria Protein Interactions Reveals Conserved Domains and Motifs That Mediate Fundamental Infection Pathways

Borrego

Torrent

2022

IJMS

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Adhesion and colonization of host cells by pathogenic bacteria depend on protein–protein interactions (PPIs). These interactions are interesting from the pharmacological point of view since new molecules that inhibit host-pathogen PPIs would act as new antimicrobials. Most of these interactions are discovered using high-throughput methods that may display a high false positive rate. The absence of curation of these databases can make the available data unreliable. To address this issue, a comprehensive filtering process was developed to obtain a reliable list of domains and motifs that participate in PPIs between bacteria and human cells. From a structural point of view, our analysis revealed that human proteins involved in the interactions are rich in alpha helix and disordered regions and poorer in beta structure. Disordered regions in human proteins harbor short sequence motifs that are specifically recognized by certain domains in pathogenic proteins. The most relevant domain–domain interactions were validated by AlphaFold, showing that a proper analysis of host-pathogen PPI databases can reveal structural conserved patterns. Domain–motif interactions, on the contrary, were more difficult to validate, since unstructured regions were involved, where AlphaFold could not make a good prediction. Moreover, these interactions are also likely accommodated by post-translational modifications, especially phosphorylation, which can potentially occur in 25–50% of host proteins. Hence, while common structural patterns are involved in host–pathogen PPIs and can be retrieved from available databases, more information is required to properly infer the full interactome. By resolving these issues, and in combination with new prediction tools like Alphafold, new classes of antimicrobials could be discovered from a more detailed understanding of these interactions.

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Section: Resultsmentioning

confidence: 98%

Analysis of Host–Bacteria Protein Interactions Reveals Conserved Domains and Motifs That Mediate Fundamental Infection Pathways

Borrego

Torrent

2022

IJMS

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“…Several studies suggest that protein-protein interactions are fundamental for the pathogens to infect the host [ 40 , 41 ]. Hence, we also examined whether genes found to be differentially regulated during infection can be connected at the protein level.…”

Section: Resultsmentioning

confidence: 99%

Time-Resolved Transcriptional Profiling of Epithelial Cells Infected by Intracellular Acinetobacter baumannii

Asensio¹,

Rendón²,

Torrent³

2021

Microorganisms

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The rise in the number of antibiotic-resistant bacteria has become a serious threat to health, making it important to identify, characterize and optimize new molecules to help us to overcome the infections they cause. It is well known that Acinetobacter baumannii has a significant capacity to evade the actions of antibacterial drugs, leading to its emergence as one of the bacteria responsible for hospital and community-acquired infections. Nonetheless, how this pathogen infects and survives inside the host cell is unclear. In this study, we analyze the time-resolved transcriptional profile changes observed in human epithelial HeLa cells after infection by A. baumannii, demonstrating how it survives in host cells and starts to replicate 4 h post infection. These findings were achieved by sequencing RNA to obtain a set of Differentially Expressed Genes (DEGs) to understand how bacteria alter the host cells’ environment for their own benefit. We also determine common features observed in this set of genes and identify the protein–protein networks that reveal highly-interacted proteins. The combination of these findings paves the way for the discovery of new antimicrobial candidates for the treatment of multidrug-resistant bacteria.

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“…The existence of these common interactors demonstrates how pathogens evolved to cleverly debilitate their hosts, and in this manner, maintain low fitness costs as compared with the individual gene-for-gene interactions [ 189 ]. More high-throughput interactomics network studies are necessary to elucidate effector targets [ 194 , 195 , 196 ].…”

Section: Effector Targets: Beyond the Apoplastmentioning

confidence: 99%

Fungal Effectoromics: A World in Constant Evolution

Todd

Carreón-Anguiano

Islas‐Flores

et al. 2022

IJMS

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Effectors are small, secreted molecules that mediate the establishment of interactions in nature. While some concepts of effector biology have stood the test of time, this area of study is ever-evolving as new effectors and associated characteristics are being revealed. In the present review, the different characteristics that underly effector classifications are discussed, contrasting past and present knowledge regarding these molecules to foster a more comprehensive understanding of effectors for the reader. Research gaps in effector identification and perspectives for effector application in plant disease management are also presented, with a focus on fungal effectors in the plant-microbe interaction and interactions beyond the plant host. In summary, the review provides an amenable yet thorough introduction to fungal effector biology, presenting noteworthy examples of effectors and effector studies that have shaped our present understanding of the field.

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Bacteria use structural imperfect mimicry to hijack the host interactome

Cited by 11 publications

References 60 publications

Analysis of Host–Bacteria Protein Interactions Reveals Conserved Domains and Motifs That Mediate Fundamental Infection Pathways

Analysis of Host–Bacteria Protein Interactions Reveals Conserved Domains and Motifs That Mediate Fundamental Infection Pathways

Time-Resolved Transcriptional Profiling of Epithelial Cells Infected by Intracellular Acinetobacter baumannii

Fungal Effectoromics: A World in Constant Evolution

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