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Identification of OmpA, a Protein Involved in Host Cell Invasion, by Multi-Phenotypic High-Content Screening


Infectious diseases are among the major causes of mortality worldwide. Pathogens‚ invasion, colonization and persistence within their hosts depend on a tightly orchestrated cascade of events that are commonly referred to as host/pathogen interactions. These interactions are extremely diversified and every pathogen is characterized by its unique way of co-opting and manipulating host functions to its advantage. Understanding host/pathogen interactions is the key to face the threats imposed by infectious diseases and find alternative strategies to fight the emergence of multi-drug resistant pathogens. In this study, we have setup and validated a protocol for the rapid and unbiased identification of bacterial factors that regulate host/pathogen interactions. We have applied this method to the study of Coxiella burnetii, the etiological agent of the emerging zoonosis Q fever. We have isolated, sequenced and screened over 1000 bacterial mutations and identified genes important for Coxiella invasion and replication within host cells. Ultimately, we have characterized the first Coxiella invasin, which mediates bacterial internalization within non-phagocytic cells. Most importantly, our finding may lead to the development of a synthetic vaccine against Q fever.


Vyšlo v časopise: Identification of OmpA, a Protein Involved in Host Cell Invasion, by Multi-Phenotypic High-Content Screening. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004013
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004013

Souhrn

Infectious diseases are among the major causes of mortality worldwide. Pathogens‚ invasion, colonization and persistence within their hosts depend on a tightly orchestrated cascade of events that are commonly referred to as host/pathogen interactions. These interactions are extremely diversified and every pathogen is characterized by its unique way of co-opting and manipulating host functions to its advantage. Understanding host/pathogen interactions is the key to face the threats imposed by infectious diseases and find alternative strategies to fight the emergence of multi-drug resistant pathogens. In this study, we have setup and validated a protocol for the rapid and unbiased identification of bacterial factors that regulate host/pathogen interactions. We have applied this method to the study of Coxiella burnetii, the etiological agent of the emerging zoonosis Q fever. We have isolated, sequenced and screened over 1000 bacterial mutations and identified genes important for Coxiella invasion and replication within host cells. Ultimately, we have characterized the first Coxiella invasin, which mediates bacterial internalization within non-phagocytic cells. Most importantly, our finding may lead to the development of a synthetic vaccine against Q fever.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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