Figure 4.

Proposed mechanism for lysis/lytic cycle regulation in H. pylori prophages.

(a) Gene cluster of complete prophage references representative of the four main prophage populations (bold tips in Figure 2b), VNM-002 – EastAsia, POL-008 – NEurope; POR-009 – SWEurope; ALG-004 – Africa. Genes are color coded (Green – integrase; red – holin; blue – core (≥40% identity with presence in ≥ 90% of complete prophage genomes; integrase also within this group); gray – other genes). The predicted promoters are depicted with red arrows and coded with letters. The predicted gene function is shown (Grey letters for transcriptional regulators).

(b) Schematic of proposed lytic and Lysogenic cycles, based on representation of the ALG-004 prophage genome. 1: Choosing between lytic/lysogenic cycles upon infection. The repressor MarR regulates the events governing lysogeny versus lytic cycle, hypothetically binding to an AT-rich palindromic motif. The yellow hexagons contains the number of TTAA sites in the promoter region, where MarR can potentially bind, impeding gene transcription under the control of these promoters, leading to lysogeny. When MarR is not expressed in sufficient amounts, or is inactivated leads to the lytic pathway. MarR may also prevent infection by the same phage. 2: Switch to the lytic cycle. The putative histidine kinase (HK) hypothetically receives a stimulus (green arrow), inducing autophosphorylation of HK. The HK acts as the primary sensor, then the phosphate is transferred to other transcription factors to directly regulate the expression of a series of genes required for the lytic cycle. The putative phosphorylation of MarR (probable cys-phosphorylation of MarR encoded by gene 5, contains 8 cysteine residues susceptible to phosphorylation) may inactivate the repressor leading to the lytic cycle. 3: The full lytic cycle. The ArsR transcriptional regulator (homo-dimer) may regulate late gene expression. Phosphorylated ArsR may control transcription of genes beyond their baseline levels. The genes under the control of the transcriptional regulator NusG (including the lysis-cassette genes that lead to the bacterium lysis at the end of the lytic cycle) may have accelerated transcription elongation rate by suppression of specific transcription pause sites (green arrows).