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Τρίτη 19 Ιουλίου 2022

Increased sensitivity of Aggregatibacter actinomycetemcomitans to human serum is mediated by induction of a bacteriophage

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Summary

Aggregatibacter actinomycetemcomitans, a Gram-negative oral pathobiont causing aggressive periodontitis and systemic infections demonstrates serum resistance. We have identified a dsDNA tailed bacteriophage S1249, which was found from this microorganism inducible by human serum to convert into lytic state to kill the bacterium. This phage demonstrated active transcripts when exposed to human serum: 20% of genes were up regulated greater than 10 folds and 45% of them were up regulated 5–10 folds, when the bacterium was grown in the presence of human serum compared to without. Transcriptional activation when grown in equine serum was less pronounced. This phage demonstrated a tail with the inner rigid tubes and outer contractile sheath, features of Myoviridae spp. Further characterization revealed that the lysogenized integration of the phage in the chromosome of A. actinomycetemcomitans occurred between the genes encoding for cold-shock DNA-binding domain-con taining protein (csp) and glutamyl-tRNA synthetase (gltX). Both phage DNA integrated lysogeny and non-integrated pseudolysogeny were identified in the infected bacterium. A newly generated, lysogenized strain using this phage displayed similar attributes, including 63% growth inhibition compared to its isogenic phage-free strain when in the presence of human serum. Our data suggest that bacteriophage S1249 can be induced in the presence of human serum and enters the lytic cycle, which reduces the viability of infected bacteria in vivo.

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