Abstract
Shiga toxin-converting bacteriophages (or Stx phages) are responsible for virulence of enterohemorrhagic Escherichia coli strains. Although they belong to the group of lambdoid phages, which have served as models in studies on DNA replication mechanisms, details of regulation of replication of Stx phage genomes are poorly understood. Despite high similarity of their replication regions to that of phage lambda, considerable differences occur between them. Here, we present a comparison of origins of replication and O proteins of lambda and selected Stx phages (phages P27 and 933W). Stx initiator proteins, similarly to the lambda O protein, exist in the form of dimers. Only 4 iteron sequences are strongly bound in vitro by the O proteins, despite the presence of 6 such fragments in the Stx ori, while the function of the other two iterons is still crucial for transformation of E. coli wild-type strain by the P27-derived lambdoid plasmid. As these sequences are found in the gene coding for Stx O proteins, the sequences of these proteins themselves are also extended compared to lambda phage. Therefore, proteins O of Stx phages P27 and 933W have 13 additional amino acids. They can act as a space barrier, thus affecting the lesser packing of the O-some Stx complex compared to the structure found in lambda. Such structure of the DNA replication initiation complex may determine its lesser dependence on the processes occurring in the host cell, including transcriptional activation of the origin. Differences between molecular processes occurring during formation of replication complexes in lambda and Stx phages may indicate the specialization of the latter phages and their adaptation to specific environmental conditions where quick genetic switches are crucial.
Highlights
Escherichia coli constitutes crucial component of the natural microbiota of the human and warm-blooded animals intestine (Actis, 2014)
Since DNA replication of Stx phages appears to be necessary for effective production of Shiga toxins by Shiga toxin-producing E. coli (STEC) strains (NejmanFalenczyk et al, 2012; Nowicki et al, 2013; Balasubramanian et al, 2019), understanding of the regulation of this process is crucial for basic science and for applications related to development of novel anti-STEC treatments
Replication regions of genomes of Stx phages are highly similar to that of bacteriophage λ, there are important differences which result in significantly altered regulation of Stx phage DNA replication relative to λ (Nejman et al, 2009, 2011; Nowicki et al, 2015)
Summary
Escherichia coli constitutes crucial component of the natural microbiota of the human and warm-blooded animals intestine (Actis, 2014). Shiga toxin-producing E. coli (STEC) strains, synthesizing one of the strongest toxins, are among the most dangerous pathogens (Paletta et al, 2020). Infections with these strains are dangerous, because they can cause severe complications, while available antibacterial therapies are often not effective against those pathogens (Karmali, 2018). The latter problem is caused by two factors: firstly, STEC strains are often resistant to many antibiotics, secondly, the use of antimicrobials may be counterproductive, as some of them may enhance expression of Shiga toxins genes. There are examples of many outbreaks caused by STEC which resulted in severe complications in thousands of patients and relatively many deaths (Devleesschauwer et al, 2019; Kintz et al, 2019)
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