The ea22 gene of lambdoid phages: preserved prolysogenic function despite of high sequence diversity

Abstract

The exo-xis region of lambdoid phages contains open reading frames and genes that appear to be evolutionarily important. However, this region has received little attention up to now. In this study, we provided evidence that ea22, the largest gene of this region, favors the lysogenic pathway over the lytic pathway in contrast to other characterized exo-xis region genes including ea8.5, orf61, orf60a, and orf63. Our assays also suggest some functional analogies between Ea22 and the phage integrase protein (Int). While it is unsurprising that Ea22 operates similarly in both λ and Stx phages, we have observed some distinctions that may arise from considerable sequence dissimilarity at the carboxy termini of each protein. Keywords Exo-xis region • Lambdoid phages development • Shiga toxin-producing Escherichia coli (STEC)

Molecular Modeling the Proteins from the exo-xis Region of Lambda and Shigatoxigenic Bacteriophages

“…Gdansk). Throughout their studies, they have used four functional assays to assign the behavior of a given exo-xis gene as either pro-lysogenic or pro-lytic [ 24 , 25 , 26 , 27 ]. Two of the assays examine the time it takes for the lytic cycle to begin either from the onset of infection or the induction of lysogens by stressors such as hydrogen peroxide, antibiotics, and ultraviolet light.…”

“…The ea22 gene provides some contrast to the three exo-xis genes that precede it. Not only is it the largest protein of the exo-xis region and multidomain in composition [ 52 ], but its function also favors lysogenic development over lytic development [ 27 ]. With this function in mind, Ea22 may serve as a new focal point for understanding how Stx + phage lytic program can be delayed during EHEC infections to limit the release of Shiga toxin.…”

Bacteriophages of Shiga Toxin-Producing Escherichia coli and Their Contribution to Pathogenicity

“…Ongoing research will most probably reveal even more transcriptomic changes upon Stx phage carriage since we have only begun to understand the function of some of the genes encoded in Stx phages. This is the case for phage φ24-B, which possesses five conserved genes within the exo - xis region; ea22 , orf60a, orf61, orf63, and orf73 [ 142 , 143 , 144 , 145 ]. ea22 and orf73 promote the maintenance of the lysogenic state, orf63 represses and delays phage induction, while orf60 and orf61 seem to promote phage induction since their deletions significantly delay the induction of the Stx φ24B prophage [ 142 , 143 , 144 , 145 , 146 ].…”

Ea22 Proteins from Lambda and Shiga Toxin-Producing Bacteriophages Balance Structural Diversity with Functional Similarity

“…8,9 A relatively unknown region between the exo and xis genes of λ and Stx + phages is known to affect the host cell-cycle 10,11 and the lysogenic−lytic transition 12,13 yet, paradoxically, is also dispensable for normal viral development. This so-called exo− xis region consists of four open reading frames termed ea22, 14 orf 73, orf61, 15 and orf63. 16 While the overall number of exo− xis region genes in Stx + phages can be larger, these four genes are conserved, suggesting that there may be some evolutionary pressure to maintain them.…”

“…Unlike other exo−xis genes studied to date that accelerate the development of the lytic state, 15,16,18 ea22 promotes the maintenance of the lysogenic state. 14 Before we embarked on this study, it was not known if ea22 even encoded a protein although the functional data appeared to suggest it was the case. With a set of expressed and purified Ea22 proteins and protein fragments from λ phage and two representative Stx + phages, φP27 19 and φ24 B, 12 we demonstrate that Ea22 is a multidomain protein that can be considered in terms of an amino-terminal region, a central coiled-coil region, and a carboxy-terminal region.…”