3 years ago

In vivo virulence characterization of pregnancy-associated Listeria monocytogenes infections.

Jennifer R Robbins, Anna I Bakardjiev, Holly A Morrison, David Lowe
Listeria monocytogenes is a foodborne pathogen that infects the placenta and can cause pregnancy complications. Listeriosis infections usually occur as sporadic infections, but large outbreaks are also reported. Virulence from clinical isolates is rarely analyzed due to the large number of animals required, but this knowledge could help guide the response to an outbreak. We implemented a DNA barcode system using signature tags that allowed us to efficiently assay variations in virulence across a large number of isolates. We tested 77 signature-tagged clones of clinical L. monocytogenes strains from 72 infected human placentas and five immunocompromised patients, all isolated since 2000. These strains were tested for virulence in a modified competition assay in comparison to the laboratory strain 10403S. We used two in vivo models of listeriosis: the non-pregnant mouse and the pregnant guinea pig. Strains that were frequently found at high abundance within infected organs were considered "hypervirulent," while strains frequently found at low abundance were considered "hypovirulent." Virulence split relatively evenly among hypovirulent, hypervirulent, and strains equally virulent to 10403S. The laboratory strain was found to have an intermediate virulence phenotype, supporting its suitability for pathogenesis studies. Further, we found that splenic and placental virulence are closely linked in both guinea pig and mouse models. This suggests that outbreak and sporadic pregnancy-associated L. monocytogenes are not generally more virulent than lab reference strains. However, some strains did show consistent and reproducible virulence differences, suggesting that their further study may reveal deeper insights into the biological underpinnings of listeriosis.

Publisher URL: http://doi.org/10.1128/IAI.00397-18

DOI: 10.1128/IAI.00397-18

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